bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetics of murine craniofacial morphology: diallel analysis of the eight founders of the Collaborative Cross
Authors: Percival Christopher J. , Liberton Denise K. , Pardo‐Manuel de Villena Fernando , Spritz Richard , Marcucio Ralph , Hallgrímsson Benedikt
Published: October 2015

Using eight inbred founder strains of the mouse Collaborative Cross (CC) project and their reciprocal F1 hybrids, we quantified variation in craniofacial morphology across mouse strains, explored genetic contributions to craniofacial variation that distinguish the founder strains, and tested whether specific or summary measures of craniofacial shape display stronger additive genetic contributions. This study thus provides critical information about phenotypic diversity among CC founder strains and about the genetic contributions to this phenotypic diversity, which is relevant to understanding the basis of variation in standard laboratory strains and natural populations. Craniofacial shape was quantified as a series of size‐adjusted linear dimensions (RDs) and by principal components (PC) analysis of morphological landmarks captured from computed tomography images from 62 of the 64 reciprocal crosses of the CC founder strains. We first identified aspects of skull morphology that vary between these phenotypically ‘normal’ founder strains and that are defining characteristics of these strains. We estimated the contributions of additive and various non‐additive genetic factors to phenotypic variation using diallel analyses of a subset of these strongly differing RDs and the first eight PCs of skull shape variation. We find little difference in the genetic contributions to RD measures and PC scores, suggesting fundamental similarities in the magnitude of genetic contributions to both specific and summary measures of craniofacial phenotypes. Our results indicate that there are stronger additive genetic effects associated with defining phenotypic characteristics of specific founder strains, suggesting these distinguishing measures are good candidates for use in genotype–phenotype association studies of CC mice. Our results add significantly to understanding of genotype–phenotype associations in the skull, which serve as a foundation for modeling the origins of medically and evolutionarily relevant variation.
Graduate nurses’ knowledge of the functions and limitations of pulse oximetry
Authors: Seeley Marie‐Claire , McKenna Lisa , Hood Kerry
Published: September 2015

Aims and objectives

To examine nursing graduates’ knowledge of functions and limitations of pulse oximetry.

Background

Pulse oximetry is a technology ubiquitous in its use in modern clinical settings. Although the technology's ability to accurately reflect hypoxaemia in patients has been established, its contribution to improving patient outcomes is less certain. In addition, experienced nurses have previously demonstrated poor understanding of the limitations of the technology. Pregraduate education has been identified as a potential source of knowledge deficit and has been recommended by authors as an important target of investigation.

Design

Cross‐sectional, comparative, multicentre study.

Method

A previously published and validated tool was used with the addition of eight clinical scenario questions which were validated by an expert panel. Convenience sampling was used to select participants to form one cohort of newly graduated nurses (Cohort 1:n= 210) and a second cohort of nurses completing their intensive postgraduate clinical year (Cohort 2:n= 97).

Results

Significant deficits relating to the theoretical factors that affect pulse oximetry application and interpretation were identified. Results suggest some knowledge is negatively correlated with clinical experience and that pregraduate university education appears to influence the ability to effectively apply pulse oximetry knowledge to clinical scenarios.

Conclusions

This study provides insight into pulse oximetry knowledge acquisition and deficits of graduate nurses which may inform pre‐ and postgraduate nurse education. In particular, it suggests that some pulse oximetry knowledge and clinical application of knowledge is not enhanced by clinical experience but rather is currently gained through pregraduate experiences.

Relevance to clinical practice

Inappropriate utilisation and interpretation of pulse oximetry places patients at risk of mismanagement and undetected deterioration. Improvement in pregraduate education around the appropriate use of pulse oximetry may reduce clinical costs, reduce incidents of failure to rescue and improve patient outcomes.
Institutional Regime, Opportunity Space and Organizational Path Constitution: Case Studies of the Conversion of Military Firms in China
Authors: Jing Runtian , Benner Mary
Published: September 2015

This study examines organizational path constitution from an institutional regime view. The research setting is the conversion of military firms to the civilian market in China since the country's economic reform in 1978. We begin with a questionnaire survey to better understand the situation and context of military conversion, and then conducted an embedded multiple‐case study method that shows how different patterns of organizational path constitution arise from a process of change efforts, change outcomes and opportunity space. Our context further allows us to examine how heterogeneous locally‐based institutional regimes affect the opportunity space of embedded organizations, enabling or constraining their change actions. The overall contribution is a theoretical model that reveals the relations between heterogeneous institutional regimes, opportunity spaces and organizational path constitution. Our findings have implications for the path dependence literature.
Patients’ experience of partial tooth loss and expectations to treatment: a qualitative study in Danish and Swedish patients
Authors: Øzhayat E. B. , Åkerman S. , Lundegren N. , Öwall B.
Published: October 2015

Knowledge of impairments, wishes and expectations is essential to make correct decisions regarding oral rehabilitation. The purpose of this study was to investigate discomforts, wishes and expectations in patients’ with partial edentulism before entering oral rehabilitation. In Copenhagen, Denmark, and Malmö, Sweden, respectively, 20 patients with partial edentulism seeking rehabilitation were interviewed in a semistructured qualitative manner. The interviews were transcribed and analysed yielding overall domains. Six themes appeared as overall domains: (i) experienced impairments, (ii) experienced social awareness, (iii) expectation to treatment, (iv) expectation to durability/survival, (v) coping strategies dealing with the tooth loss including explanations of the tooth loss and (vi) modifications to experienced impairment. The impairments were mostly experienced as problems in social settings. Most participants expressed a simple wish to function normally; a fixed solution was preferred. Many Danish participants accepted a removable solution whereas only few Swedish participants did so. The domains ‘coping strategies’ and ‘modifications’ were not part of the chosen topics of interest, indicating a high wish of the participants to explain their tooth loss and how they coped with it. In conclusion, a large degree of social impairment was found in the patient group along with several coping strategies. The impairments were modified by a number of factors indicating that highly individualised care and treatment is needed. A state of normality was described as the primary treatment wish with a higher acceptance of removable solutions in Denmark than in Sweden. For final decision‐making, surrounding factors seemed to influence the patients’ choices.
Biometric Modeling of Gene‐Environment Interplay: The Intersection of Theory and Method and Applications for Social Inequality
Authors: South Susan C. , Hamdi Nayla R. , Krueger Robert F.
Published: October 2015

For more than a decade, biometric moderation models have been used to examine whether genetic and environmental influences on individual differences might vary within the population. These quantitative Gene × Environment interaction models have the potential to elucidate not only when genetic and environmental influences on a phenotype might differ, but also why, as they provide an empirical test of several theoretical paradigms that serve as useful heuristics to explain etiology—diathesis‐stress, bioecological, differential susceptibility, and social control. In the current article, we review how these developmental theories align with different patterns of findings from statistical models of gene‐environment interplay. We then describe the extant empirical evidence, using work by our own research group and others, to lay out genetically informative plausible accounts of how phenotypes related to social inequality—physical health and cognition—might relate to these theoretical models.
Emergency department visits and revisits for nontraumatic dental conditions in Iowa
Authors: Darling Brian G. , Singhal Astha , Kanellis Michael J.
Published: October 2015

Objectives

To examine the characteristics associated with emergency department (ED) utilization in Iowa for nontraumatic dental conditions (NTDCs), and those associated with having multiple visits to the ED for NTDCs before the Medicaid expansion program in Iowa.

Methods

State Emergency Department Database for Iowa was used for 2012, which comprised of all outpatient ED visits in the state. Logistic regression was used for bivariate and multivariable analyses to model the odds of visiting the ED for NTDCs, relative to other conditions, and odds of visiting the ED multiple times relative to a single time in 2012 for NTDCs. The hospital charges associated with the NTDC ED visits were also examined.

Results

ED visits for NTDCs comprised 1.41% of all ED visits in Iowa during 2012 with a mean charge of $557. Of the patients presenting for NTDCs in 2012, 17% presented multiples times. Young adults, Medicaid enrollees or uninsured, and those residing in metropolitan areas had greater odds of presenting to the EDs for NTDCs compared with other conditions, and presenting multiple times to EDs for NTDCs. Those with more chronic conditions also had greater odds of repeatedly visiting the ED for NTDCs.

Conclusions

Low‐income young adults in Iowa rely on EDs for their dental needs that can have substantial costs. The Dental Wellness Plan (DWP) is intended to facilitate dental care access by providing dental coverage to low‐income Iowans. This study provides baseline data that will be used to evaluate the success of DWP in improving access to dental care.
Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin
Authors: Bauquier J.R. , Boston R.C. , Sweeney R.W. , Wilkins P.A. , Nolen‐Walston R.D.
Published: October 2015

Background

Gentamicin is an aminoglycoside antimicrobial commonly used in horses at 6.6 mg/kgIVonce daily. Therapeutic drug monitoring (TDM) can confirm desired peak concentration is reached for common bacterial isolates, and detect toxicosis associated with high trough values.

Objectives

Determine the relationship between gentamicin dose and plasma concentration in hospitalized horses, and identify a starting dose range to achieve peaks > 32 μg/mL.

Animals

Sixty‐five horses (2002–2010) receiving once‐daily gentamicin withTDMperformed (N = 99 sets).

Methods

Retrospective study. Data from hospitalized horses including weight, dose, plasma peak, and trough gentamicin concentration, creatinine concentrations and presence of focal or systemic disease were collected from medical records. Peak concentrations measured 25–35 minutes after administration were included (N = 77). Data were divided into low (<7.7 mg/kg), medium (7.7–9.7 mg/kg) and high (>9.7 mg/kg) dose groups, and were grouped by the horse having focal or systemic disease.

Results

Peak concentrations resulting from doses ≥7.7 mg/kg were 5.74 μg/mL (SE2.1 μg/mL) greater than peaks from doses <7.7 mg/kg (P= .007). Peak concentrations was 3.6 times more likely to be >32 μg/mL if dose was ≥7.7 mg/kg (P= .04). There were no significant effects of dose on trough or creatinine concentration. At a given dose, horses with focal disease had higher peaks than those with systemic disease (P= .039).

Conclusions and Clinical Importance

These data suggest gentamicin dosage should be individually determined in horses usingTDM, but support an initial once‐daily dose of 7.7–9.7 mg/kg IV to achieve peaks >32 μg/mL and trough concentrations <2 μg/mL. Further studies evaluating the safety of doses >6.6 mg/kg are required.
The Association of Endothelin‐1 Signaling with Bone Alkaline Phosphatase Expression and Protumorigenic Activities in Canine Osteosarcoma
Authors: Neumann Z.L. , Pondenis H.C. , Masyr A. , Byrum M.L. , Wycislo K.L. , Fan T.M.
Published: October 2015

Background

Canine osteosarcoma (OS) is an aggressive sarcoma characterized by pathologic skeletal resorption and pulmonary metastases. A number of negative prognostic factors, including bone alkaline phosphatase, have been identified in dogs withOS, but the underlying biologic factors responsible for such observations have not been thoroughly investigated. Endothelin‐1‐mediated signaling is active during bone repair, and is responsible for osteoblast migration, survival, proliferation, and bone alkaline phosphatase expression.

Hypothesis

The endothelin‐1 signaling axis is active in canineOScells, and this pathway is utilized by malignant osteoblasts for promoting cellular migration, survival, proliferation, and bone alkaline phosphatase activities.

Animals

45 dogs with appendicularOS.

Methods

The expressions of endothelin‐1 and endothelinAreceptor were studied inOScell lines and in samples from spontaneously occurring tumors. Activities mediated by endothelin‐1 signaling were investigated by characterizing responses in 3OScell lines. In 45 dogs withOS, bone alkaline phosphatase concentrations were correlated with primary tumor osteoproductivity.

Results

CanineOScells express endothelin‐1 and endothelinAreceptor, and this signaling axis mediatesOSmigration, survival, proliferation, and bone alkaline phosphatase activities. InOS‐bearing dogs, circulating bone alkaline phosphatase activities were positively correlated with primary tumor relative bone mineral densities.

Conclusions and Clinical Importance

CanineOScells express endothelin‐1 and functional endothelinAreceptors, with the potential for a protumorigenic signaling loop. Increases in bone alkaline phosphatase activity are associated with osteoblasticOSlesions, and might be an epiphenomenon of active endothelin‐1 signaling or excessive osteoproduction within the localized bone microenvironment.
ROBUST FUNDAMENTAL THEOREM FOR CONTINUOUS PROCESSES
Authors: Biagini Sara , Bouchard Bruno , Kardaras Constantinos , Nutz Marcel
Published: October 2015

We study a continuous‐time financial market with continuous price processes under model uncertainty, modeled via a family of possible physical measures. A robust notion of no‐arbitrage of the first kind is introduced; it postulates that a nonnegative, nonvanishing claim cannot be superhedged for free by using simple trading strategies. Our first main result is a version of the fundamental theorem of asset pricing: holds if and only if every admits a martingale measure that is equivalent up to a certain lifetime. The second main result provides the existence of optimal superhedging strategies for general contingent claims and a representation of the superhedging price in terms of martingale measures.
Association of serum sodium levels with all‐cause and cardiovascular mortality in chronic kidney disease: Results from a prospective observational study
Authors: Chiu Diana Yuan Yng , Kalra Philip A , Sinha Smeeta , Green Darren
Published: October 2015

Aims

The prevalence of hyponatraemia in the outpatient setting has not been thoroughly explored, and little is known about the prognostic implication of dysnatraemia in chronic kidney disease (CKD) patients, in particular accommodating the effect of concurrent medications.

Methods

This is a prospective observational study of non‐dialysis‐dependent CKD patients managed in a nephrology clinic. Patients enrolled between 2002 and 2012 in the Chronic Renal Insufficiency Standards Implementation Study were assessed. Survival analyses were performed using baseline sodium and 12‐month time‐averaged sodium, with adjustment for co‐morbid diseases, laboratory findings and concurrent medications.

Results

At baseline (n = 2093), mean estimated glomerular filtration rate was 32.8 ± 15.9 ml/min per 1.73 m2, median age was 67 (interquartile range 56–75) years and median serum sodium concentration was 140 (138–142) mmol/l. After a follow up of 41 (18–67) months, there were 684 deaths, 174 from cardiovascular causes; 1925 time‐averaged sodium values were analysed. In the Cox multivariate adjusted regression, baseline hyponatraemia, but not hypernatraemia, was independently associated with all‐cause mortality (hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.02–1.78, P = 0.04, and HR 1.15, 95% CI 0.84–1.57, P = 0.39, respectively). This was similarly the case for time‐averaged hyponatraemia and hypernatraemia (HR 2.15, 95% CI 1.59–2.91, P < 0.01, and HR 1.47, 95% CI 0.93–2.38, P = 0.10, respectively). However, the association of baseline and time‐averaged hyponatraemia with cardiovascular mortality was not significant.

Conclusion

Hyponatraemia in the ambulatory setting is associated with all‐cause but not cardiovascular mortality in CKD, independent of concomitant medications and co‐morbidities.
QseBC, a two‐component bacterial adrenergic receptor and global regulator of virulence in Enterobacteriaceae and Pasteurellaceae
Authors: Weigel W.A. , Demuth D.R.
Published: October 2015

The QseBC two‐component system (TCS) is associated with quorum sensing and functions as a global regulator of virulence. Based on sequence similarity within the sensor domain and conservation of an acidic motif essential for signal recognition, QseBC is primarily distributed in the Enterobacteriaceae and Pasteurellaceae. In Escherichia coli, QseC responds to autoinducer‐3 and/or epinephrine/norepinephrine. Binding of epinephrine/norepinephrine is inhibited by adrenergic antagonists; hence QseC functions as a bacterial adrenergic receptor. Aggregatibacter actinomycetemcomitans QseC is activated by a combination of epinephrine/norepinephrine and iron, whereas only iron activates the Haemophilus influenzae sensor. QseC phosphorylates QseB but there is growing evidence that QseB is activated by non‐cognate sensors and regulated by dephosphorylation via QseC. Interestingly, the QseBC signaling cascades and regulons differ significantly. In enterohemorrhagic E. coli, QseC induces expression of a second adrenergic TCS and phosphorylates two non‐cognate response regulators, each of which induces specific sets of virulence genes. This signaling pathway integrates with other regulatory mechanisms mediated by transcriptional regulators QseA and QseD and a fucose‐sensing TCS and likely controls the level and timing of virulence gene expression. In contrast, A. actinomycetemcomitans QseC signals through QseB to regulate genes involved in anaerobic metabolism and energy production, which may prime cellular metabolism for growth in an anaerobic host niche. QseC represents a novel target for therapeutic intervention and small molecule inhibitors already show promise as broad‐spectrum antimicrobials. Further characterization of QseBC signaling may identify additional differences in QseBC function and inform further development of new therapeutics to control microbial infections.
Targeted gene exchange in plant cells mediated by a zinc finger nuclease double cut
Authors: Schneider Katja , Schiermeyer Andreas , Dolls Anja , Koch Natalie , Herwartz Denise , Kirchhoff Janina , Fischer Rainer , Russell Sean M. , Cao Zehui , Corbin David R. , Sastry‐Dent Lakshmi , Ainley W. Michael , Webb Steven R. , Schinkel Helga , Schillberg Stefan
Published: October 2015

Genome modification by homology‐directed repair (HDR) is an attractive tool for the controlled genetic manipulation of plants. Here, we report the HDR‐mediated gene exchange of expression cassettes in tobacco BY‐2 cells using a designed zinc finger nuclease (ZFN). The target contained a 7‐kb fragment flanked by two ZFN cutting sites. That fragment was replaced with a 4‐kb donor cassette, which integrates gene markers for selection (kanamycin resistance) and for scoring targeting (red fluorescent protein, RFP). Candidates resulting from cassette exchange were identified by molecular analysis of calli generated by transformation via direct DNA delivery. The precision of HDR‐mediated donor integration was evaluated by Southern blot analysis, sequencing of the integration locus and analysis of RFP fluorescence by flow cytometry. Screening of 1326 kanamycin‐resistant calli yielded 18 HDR events, 16 of which had a perfect cassette exchange at the insert junction and 13 of which produced functional RFP. Our results demonstrate that ZFN‐based HDR can be used for high frequency, precise, targeted exchange of fragments of sizes that are commercially relevant in plants.
Operational Impact of Service Innovations in Multi‐Step Service Systems
Authors: Tong Chunyang , Nagarajan Mahesh , Cheng Yuan
Published: October 2015

Service quality is an important attribute that is used to characterize many service systems. In this study, we examine a service system with two consecutive steps that have shared resources. The service process consists of a base service (first step in the process) followed by a second step that adds additional value. We first look at a social surplus maximizing service provider (SP) who decides the optimal service capacity and re‐optimizes in response to changes in the speed of service of the first step due to local innovations. Our main objective is to explore using simple and stylized models, the effect on the service system of local innovations in step 1 that decrease this step's service times. We find that the effect of such innovations can sometimes lead to the worsening of certain critical service quality measures when SPs are monopolists. Next, using a model of competition, we find that this effect continues to hold in settings where SPs compete for arrivals. Our results have interesting consequences for many service systems and may help explain some of the unintended effects of service innovations reported in the literature.
Capacity Allocation and Pricing Strategies for New Wireless Services
Authors: Duan Lingjie , Shou Biying , Huang Jianwei
Published: October 2015

Indoor cell phone users often suffer poor connectivity. One promising solution to this issue, femtocell technology, has been rapidly developed and deployed over the past few years. One of the biggest challenges facing femtocell deployment is the lack of a clear business model. This study investigates the economic incentive for cellular operators (also called macrocell operators) to enable femtocell service by leasing spectrum resources to independent femtocell operators. We model the interactions between a macrocell operator, a femtocell operator, and end‐users as a three‐stage dynamic game, and derive the equilibrium pricing and capacity allocation decisions. We show that when spectrum resources are very limited, the macrocell operator has more incentive to lease spectrum to the femtocell operator, as femtocell services can help cover more users and improve the utilization efficiency of the limited spectrum resource. However, when the total spectrum resource is large, femtocell service offers significant competition to macrocell service and, as a result, the macrocell operator has less incentive to enable femtocell service. We also show the impact of the additional operational costs and limited coverage of femtocell service on equilibrium decisions, consumer surplus, and social welfare.
Managing Inventory with Cash Register Information: Sales Recorded but Not Demands
Authors: Bensoussan Alain , Çakanyildirim Metin , Li Meng , Sethi Suresh P.
Published: October 2015

Inventory inaccuracy is common in many businesses. While retailers employ cash registers to enter incoming orders and outgoing sales, inaccuracy arises because they do not record invisible demand such as spoilage, damage, pilferage, or returns. This setting results in incomplete inventory and demand information. An important inventory control problem therefore is to maximize the total expected discounted profit under this setting. Allowing for dependence between demand and invisible demand, we obtain the associated dynamic programming equation with an infinite‐dimensional state space, and reduce it to a simpler form by employing the concept of unnormalized probability. We develop an analytical upper bound on the optimal profit as well as an iterative algorithm for an approximate solution of the problem. We compare profits of the iterative solution and the myopic solution, and then to the upper bound. We see that the iterative solution performs better than the myopic solution, and significantly so in many cases. Furthermore, it gives a profit not far from the upper bound, and is therefore close to optimal. Using our results, we also discuss meeting inventory service levels.
Risk, Process Maturity, and Project Performance: An Empirical Analysis of US Federal Government Technology Projects
Authors: Mishra Anant , Das Sidhartha R. , Murray James J.
Published: October 2015

In recent years, there has been increasing pressure on the US federal government to reduce spending and improve the management of its technology projects. Mitigating the adverse impact of risks on the performance of these projects presents a significant challenge for its stakeholders. Our research examines this challenge in two steps. First, we identify and define a set of salient risks in federal technology projects—specifically, complexity risk and contracting risk in the planning process, and execution risk in the execution process. Next, we investigate whether higher levels of process maturity, assessed by the Capability Maturity Model Integration (CMMI) framework, mitigate the negative effect of project risks on project performance. The analysis of time‐series data collected from 82 federal technology projects across 519 quarterly time periods indicates that each of the three types of risks has a significant negative effect on project performance. This finding highlights the practical significance of managing these risks in the federal technology project context. Further, we find that increasing levels of process maturity attenuate the negative effect of project risks on the performance of federal technology projects. However, the attenuation effects are consequential only at high levels of project risks; at low levels of project risk, increasing levels of process maturity can adversely affect project performance. To demonstrate the financial implications of increasing process maturity levels in federal technology projects, we examine the magnitude of project cost savings (and overruns) across different levels of CMMI and project risks. In summary, our study contributes to the sparse literature on public sector operations by addressing the understudied context of federal technology projects, and provides a nuanced examination of the implications of process maturity in managing the risk to performance relationship in such projects.
Photo‐Thermo‐Mechanical Behaviour Under Quasi‐Static Tensile Conditions of a PMMA‐Core Optical Fibre
Authors: Pérez‐Castellanos J. L. , Montero D. S. , Vázquez C. , Zahr‐Viñuela J. , González M.
Published: October 2015

As the optical power transmitted by an optical fibre under tensile stress varies with strain, it can be used as a sensor for strain monitoring in structural elements. In the present work, quasi‐static tensile tests of step index polymer optical fibres (POF) with simultaneous measurement of surface temperature and optical power are described. Young's modulus, yield stress and tensile strength are derived from experimental tests. Morphological characterization of the POF fibres using scanning electron microscope images and differential calorimetry technique is performed. The contributions of both elastic and plastic strain components to the variation of temperature and optical power loss are also estimated. The evolution of the POF mechanical properties as well as that of temperature and optical power loss is explained in terms of the progressive relative movement and alignment of the molecular chains in the direction of the applied load. Strain, temperature and optical power loss are then correlated.
Segmentation and kinematics of the North America‐Caribbean plate boundary offshore Hispaniola
Authors: Leroy Sylvie , Ellouz‐Zimmermann Nadine , Corbeau Jordane , Rolandone Frédérique , de Lépinay Bernard Mercier , Meyer Bertrand , Momplaisir Roberte , Granja Bruña José‐Luis , Battani Anne , Baurion Céline , Burov Evgueni , Clouard Valérie , Deschamps Rémy , Gorini Christian , Hamon Youri , Lafosse Manfred , Leonel Jottin , Le Pourhiet Laetitia , Llanes Estrada Pilar , Loget Nicolas , Lucazeau Francis , Pillot Daniel , Poort Jeffrey , Tankoo Kevin R. , Cuevas José‐Luis , Alcaide José‐Fernando , Jean Poix Claude , Muñoz‐Martin Alfonso , Mitton Serge , Rodriguez Yamil , Schmitz Julien , Seeber Leonardo , Carbo‐Gorosabel Andres , Muñoz Santiago
Published: October 2015

We explored the submarine portions of the Enriquillo–Plantain Garden Fault zone (EPGFZ) and the Septentrional–Oriente Fault zone (SOFZ) along the Northern Caribbean plate boundary using high‐resolution multibeam echo‐sounding and shallow seismic reflection. The bathymetric data shed light on poorly documented or previously unknown submarine fault zones running over 200 km between Haiti and Jamaica (EPGFZ) and 300 km between the Dominican Republic and Cuba (SOFZ). The primary plate‐boundary structures are a series of strike‐slip fault segments associated with pressure ridges, restraining bends, step overs and dogleg offsets indicating very active tectonics. Several distinct segments 50–100 km long cut across pre‐existing structures inherited from former tectonic regimes or bypass recent morphologies formed under the current strike‐slip regime. Along the most recent trace of theSOFZ, we measured a strike‐slip offset of 16.5 km, which indicates steady activity for the past ~1.8 Ma if its currentGPS‐derived motion of 9.8 ± 2 mm a−1has remained stable during the entire Quaternary.
Intestinal amoebiasis in a patient with acute graft‐versus‐host disease after allogeneic bone marrow transplantation successfully treated by metronidazole
Authors: Numata A. , Itabashi M. , Kishimoto K. , Motohashi K. , Hagihara M. , Kuwabara H. , Tanaka M. , Kato H. , Chiba S. , Kunisaki R. , Fujisawa S.
Published: October 2015

Amoebiasis has rarely been reported in patients undergoing hematopoietic stem cell transplantation, although it is a world‐wide infection and extremely common. We present a case of intestinal amoebiasis unexpectedly revealed by colonoscopy after allogeneic bone marrow transplantation from a human leukocyte antigen‐mismatched unrelated donor for acute myeloid leukemia arising from chronic myelomonocytic leukemia and successfully treated by metronidazole.
A knowledge‐based molecular screen uncovers a broad‐spectrum OsSWEET14 resistance allele to bacterial blight from wild rice
Authors: Hutin Mathilde , Sabot François , Ghesquière Alain , Koebnik Ralf , Szurek Boris
Published: October 2015

Transcription activator‐like (TAL) effectors are type III‐delivered transcription factors that enhance the virulence of plant pathogenic Xanthomonas species through the activation of host susceptibility (S) genes. TAL effectors recognize their DNA target(s) via a partially degenerate code, whereby modular repeats in the TAL effector bind to nucleotide sequences in the host promoter. Although this knowledge has greatly facilitated our power to identify new S genes, it can also be easily used to screen plant genomes for variations in TAL effector target sequences and to predict for loss‐of‐function gene candidates in silico. In a proof‐of‐principle experiment, we screened a germplasm of 169 rice accessions for polymorphism in the promoter of the major bacterial blight susceptibility S gene OsSWEET14, which encodes a sugar transporter targeted by numerous strains of Xanthomonas oryzae pv. oryzae. We identified a single allele with a deletion of 18 bp overlapping with the binding sites targeted by several TAL effectors known to activate the gene. We show that this allele, which we call xa41(t), confers resistance against half of the tested Xoo strains, representative of various geographic origins and genetic lineages, highlighting the selective pressure on the pathogen to accommodate OsSWEET14 polymorphism, and reciprocally the apparent limited possibilities for the host to create variability at this particular S gene. Analysis of xa41(t) conservation across the Oryza genus enabled us to hypothesize scenarios as to its evolutionary history, prior to and during domestication. Our findings demonstrate that resistance through TAL effector‐dependent loss of S‐gene expression can be greatly fostered upon knowledge‐based molecular screening of a large collection of host plants.
LUCID: A Quantitative Assay of ESCRT‐Mediated Cargo Sorting into Multivesicular Bodies
Authors: Nickerson Daniel P. , Merz Alexey J.
Published: October 2015

Endosomes are transportation nodes, mediating selective transport of soluble and transmembrane cargos to and from the Golgi apparatus, plasma membrane and lysosomes. As endosomes mature to become multivesicular bodies (MVBs), Endosomal Sorting Complexes Required for Transport (ESCRTs) selectively incorporate transmembrane cargos into vesicles that bud into the endosome lumen. Luminal vesicles and their cargoes are targeted for destruction when MVBs fuse with lysosomes. Common assays of endosomal luminal targeting, including fluorescence microscopy and monitoring of proteolytic cargo maturation, possess significant limitations. We present a quantitative assay system called LUCID (LUCiferase reporter of Intraluminal Deposition) that monitors exposure of chimeric luciferase‐cargo reporters to cytosol. Luciferase‐chimera signal increases when sorting to the endosome lumen is disrupted, and silencing of signal from the chimera depends upon luminal delivery of the reporter rather than proteolytic degradation. The system presents several advantages, including rapidity, microscale operation and a high degree of reproducibility that enables detection of subtle phenotypic differences. Luciferase reporters provide linear signal over an extremely broad dynamic range, allowing analysis of reporter traffic even at anemic levels of expression. Furthermore, LUCID reports transport kinetics when applied to inducible trafficking reporters.
Hemoglobin oxidation at functional amino acid residues during routine storage of red blood cells
Authors: Wither Matthew , Dzieciatkowska Monika , Nemkov Travis , Strop Pavel , D'Alessandro Angelo , Hansen Kirk C.
Published: October 2015

BACKGROUND

Routine storage of red blood cells (RBCs) results in the progressive accumulation of storage lesions. While the clinical relevance of these lesions is still a matter of debate, alterations to RBC morphology and biochemistry, especially in terms of energy and redox homeostasis, are likely to affect RBC physiology and functionality at a minimum. Identification of oxidative modifications that accumulate on key RBC proteins will help bridge the gap between storage induced alterations and post‐transfusion RBC viability.

STUDY DESIGN AND METHODS

Five AS‐3 units were analyzed during routine storage via one‐dimensional sodium dodecyl sulfate–polyacrylamide gel electrophoresis–nano‐high‐performance liquid chromatography coupled online with tandem mass spectrometry and advanced database searches.

RESULTS

We identified oxidative modifications to functional residues of hemoglobin (Hb) beta chain, including proximal histidine, cysteine beta 94 (counting initiator methionine in the sequence), and histidine 144. Semiquantitative analysis indicates that up to approximately 20% of total Hb could be targeted by these oxidative modifications that are overlooked by standard proteomics approaches using routine database search conditions. Progressive accumulation of oxidized residues in stored RBCs and selective accumulation in vesicles was observed, further substantiating the hypothesis that vesiculation represents a self‐protective mechanism in ageing RBCs.

CONCLUSION

Several of the oxidized residues identified play well‐established roles in heme iron coordination, 2,3‐diphosphoglycerate binding, and nitric oxide homeostasis. Further functional and structural studies are necessary to determine possible associations between these modifications and impaired gas transport homeostasis in RBCs from old units.
Pneumothorax in a dog caused by necrotizing pneumonia secondary to heatstroke
Authors: Garber Jocelyn B. , Saile Katrin , Rademacher Nathalie , Wignall James R. , McLaughlin Leslie D. , Ryan Kirk A.
Published: October 2015

Objective

To describe the clinical course, diagnostic findings, medical and surgical treatments, and outcome in a dog with spontaneous pneumothorax secondary to necrotizing pneumonia thought to be a delayed complication of heatstroke.

Case Summary

A 1.5‐year‐old Labrador Retriever developed spontaneous pneumothorax 12 days after an episode of exertional heat stroke. Computed tomography was performed and showed bilateral pneumothorax and multifocal pulmonary consolidation, especially at the lung periphery. A median sternotomy was performed, and multifocal, well‐demarcated areas of consolidated pulmonary tissue with purple discoloration were identified and resected from the right middle, right caudal, and accessory lung lobes. Histologic examination of the resected pulmonary tissue indicated necrotizing pneumonia, and bacteriologic culture of the tissue resulted in growth of Pseudomonas aeruginosa. Examination of tissue from a pectoral muscle biopsy performed at this time showed necrotizing myopathy. The dog was discharged 7 days after surgery and made a full recovery.

New or Unique Information Provided

This case report describes pneumothorax and multifocal necrotizing pneumonia as a delayed complication of heatstroke, and provides the first description of the computed tomography appearance of histologically confirmed necrotizing pneumonia in a dog. Multifocal necrotizing pneumonia with or without pneumothorax should be considered in dogs that develop respiratory distress following severe systemic illness.
Cryptic diversity in a widespread land snail: revision of the genus Xanthomelon Martens, 1860 from the Australian Monsoon Tropics (Pulmonata, Camaenidae)
Authors: Köhler Frank , Burghardt Ingo
Published: October 2015

The camaenid genus Xanthomelon is widely distributed throughout the Australian Monsoon Tropics and eastern Queensland, with nine species currently being recognised in Australia based exclusively on shell features. Due to the combination of poor taxonomic descriptions and considerable variation in shell characters, considerable confusion surrounds the number of species in the Northern Territory (NT), their key characteristics and distributions. To uncover the full taxonomic diversity of Xanthomelon in the NT, we employed molecular phylogenetics and comparative studies of morphology/anatomy. Based on the patterns of mitochondrial differentiation as well as comparative shell and penial anatomy, we demonstrate that previous studies failed to correctly delineate species. We recognise five species in the NT, of which two (X. darwinense n. sp. and X. arnhemense n. sp.) are newly described. These species have distributions that range from narrowly endemic to most widely distributed throughout most of the Australian Monsoon Tropics. The ranges of multiple species overlap extensively with each other, which is a rather unusual phenomenon amongst the Australian Camaenidae.
Noise-induced hearing loss in marine mammals: A review of temporary threshold shift studies from 1996 to 2015
Authors: Finneran James J.
Published: October 2015

One of the most widely recognized effects of intense noise exposure is a noise-induced threshold shift—an elevation of hearing thresholds following cessation of the noise. Over the past twenty years, as concerns over the potential effects of human-generated noise on marine mammals have increased, a number of studies have been conducted to investigate noise-induced threshold shift phenomena in marine mammals. The experiments have focused on measuring temporary threshold shift (TTS)—a noise-induced threshold shift that fully recovers over time—in marine mammals exposed to intense tones, band-limited noise, and underwater impulses with various sound pressure levels, frequencies, durations, and temporal patterns. In this review, the methods employed by the groups conducting marine mammal TTS experiments are described and the relationships between the experimental conditions, the noise exposure parameters, and the observed TTS are summarized. An attempt has been made to synthesize the major findings across experiments to provide the current state of knowledge for the effects of noise on marine mammal hearing.
Added value from IPCC approval sessions
Authors: Field Christopher B. , Barros Vicente R.
Published: October 2015

Flexible, creative author teams are critical
Megasupramolecules for safer, cleaner fuel by end association of long telechelic polymers
Authors: Wei Ming-Hsin , Li Boyu , David R. L. Ameri , Jones Simon C. , Sarohia Virendra , Schmitigal Joel A. , Kornfield Julia A.
Published: October 2015

Transient polymer links are better

Very long polymer molecules elongate in shearing flows. This ordering of the chains lowers the viscosity of small-molecule solvents. The chains also reduce the dangers of misting during explosive spreading of the solvents. However, the long polymer chains degrade during normal fuel handling and clog pumping equipment. Wei
et al.
used telechelic polymers—short chains with reactive end groups—to form extremely long chains in organic solvents (see the Perspective by Jaffe and Allam). These reformable polymers offer the potential for better fuel safety without the drawbacks of covalently bonded long-chain polymers.

Science
, this issue p.
72
; see also p.
32
Safer fuels by integrating polymer theory into design
Authors: Jaffe Michael , Allam Sahitya
Published: October 2015

Jet fuels are stabilized with polymers assembling in solution

[Also see Report by

Wei
et al.

]
Eyeing up a Jupiter-like exoplanet
Authors: Mawet Dimitri
Published: October 2015

Extreme adaptive optics systems enable the direct imaging of exoplanetary systems

[Also see Report by

Macintosh
et al.

]
How stable are food webs during a mass extinction?
Authors: Marshall Charles R.
Published: October 2015

Fossil data provide a detailed view of how food webs changed across the Permian-Triassic mass extinction

[Also see Report by
Roopnarine and Angielczyk
]
A tree of the human brain
Authors: Linnarsson Sten
Published: October 2015

Genomes of single neurons trace the developmental and mutational history of the brain

[Also see Report by

Lodato
et al.

]
Human IFNAR2 deficiency: Lessons for antiviral immunity
Authors: Duncan Christopher J. A. , Mohamad Siti M. B. , Young Dan F. , Skelton Andrew J. , Leahy T. Ronan , Munday Diane C. , Butler Karina M. , Morfopoulou Sofia , Brown Julianne R. , Hubank Mike , Connell Jeff , Gavin Patrick J. , McMahon Cathy , Dempsey Eugene , Lynch Niamh E. , Jacques Thomas S. , Valappil Manoj , Cant Andrew J. , Breuer Judith , Engelhardt Karin R. , Randall Richard E. , Hambleton Sophie
Published: September 2015

Human IFNAR2 deficiency causes fatal susceptibility to live viral vaccines.
DEL-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in nonhuman primates
Authors: Shin Jieun , Maekawa Tomoki , Abe Toshiharu , Hajishengallis Evlambia , Hosur Kavita , Pyaram Kalyani , Mitroulis Ioannis , Chavakis Triantafyllos , Hajishengallis George
Published: September 2015

Developmental endothelial locus–1 (DEL-1) is an endogenous homeostatic regulator of osteoclasts that blocks inflammatory bone loss in nonhuman primates.
Super model
Authors: Spiller Kara L.
Published: September 2015

A mathematical model of fluid flow in a tube allows drug delivery to precise regions of the lung.
Development of a Multiplex PCR Assay for Rapid Molecular Serotyping of Haemophilus parasuis
Authors: Howell Kate J. , Peters Sarah E. , Wang Jinhong , Hernandez-Garcia Juan , Weinert Lucy A. , Luan Shi-Lu , Chaudhuri Roy R. , Angen Øystein , Aragon Virginia , Williamson Susanna M. , Parkhill Julian , Langford Paul R. , Rycroft Andrew N. , Wren Brendan W. , Maskell Duncan J. , Tucker Alexander W.
Published: October 2015

Haemophilus parasuiscauses Glässer's disease and pneumonia in pigs. Indirect hemagglutination (IHA) is typically used to serotype this bacterium, distinguishing 15 serovars with some nontypeable isolates. The capsule loci of the 15 reference strains have been annotated, and significant genetic variation was identified between serovars, with the exception of serovars 5 and 12. A capsule locus andin silicoserovar were identified for all but two nontypeable isolates in our collection of >200 isolates. Here, we describe the development of a multiplex PCR, based on variation within the capsule loci of the 15 serovars ofH. parasuis, for rapid molecular serotyping. The multiplex PCR (mPCR) distinguished between all previously described serovars except 5 and 12, which were detected by the same pair of primers. The detection limit of the mPCR was 4.29 × 105ng/μl bacterial genomic DNA, and high specificity was indicated by the absence of reactivity against closely related commensalPasteurellaceaeand other bacterial pathogens of pigs. A subset of 150 isolates from a previously sequencedH. parasuiscollection was used to validate the mPCR with 100% accuracy compared to thein silicoresults. In addition, the twoin silico-nontypeable isolates were typeable using the mPCR. A further 84 isolates were analyzed by mPCR and compared to the IHA serotyping results with 90% concordance (excluding those that were nontypeable by IHA). The mPCR was faster, more sensitive, and more specific than IHA, enabling the differentiation of 14 of the 15 serovars ofH. parasuis.
Evaluation of the Rapidec Carba NP Test for Detection of Carbapenemases in Enterobacteriaceae
Authors: Hombach Michael , von Gunten Barbara , Castelberg Claudio , Bloemberg Guido V.
Published: October 2015

This study evaluated the performance of the Rapidec Carba NP test, which was introduced recently into the market for the detection of carbapenemase production in a broad spectrum of β-lactamase-producing
Enterobacteriaceae
clinical isolates. In total, 252 clinical
Enterobacteriaceae
isolates that had been genetically characterized with respect to carbapenemase, extended-spectrum β-lactamase (ESBL), and AmpC genes were analyzed; 51/252 isolates (20.2%) were genetically confirmed to be carbapenemase producers, whereas 201/252 isolates (79.8%) were genetically negative for the presence of carbapenemase genes. The Rapidec Carba NP test was applied according to the manufacturer's instructions, and results were read after 30 and 120 min of incubation. The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Rapidec Carba NP test were 90.2%, 100%, 100%, and 97.6%, respectively, when the manufacturer's instructions were followed. Four of 5 false-negative results occurred with OXA-48-like enzymes. After an incubation time of 30 min, the sensitivity was 49%. The sensitivity increased to 100% when the recommended bacterial inoculum was doubled and the test was read strictly after 120 min of incubation. The Rapidec Carba NP test is a useful tool for the reliable confirmation of carbapenemase-producing
Enterobacteriaceae
isolates. The test should be read strictly after 120 min of incubation and the inoculum should be larger than recommended by the manufacturer.