bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum amyloid A in the diagnosis of feline sepsis
Authors: Troìa Roberta , Gruarin Marta , Foglia Armando , Agnoli Chiara , Dondi Francesco , Giunti Massimo
Published: July 2017

Systemic inflammatory response syndrome (SIRS) and sepsis can be challenging to diagnose in cats. Retrospectively, we investigated the diagnostic and prognostic potential of serum amyloid A (SAA), a major feline acute-phase protein (APP), in a population of critically ill cats with SIRS related to trauma or sepsis. A total of 56 SIRS cats (trauma n = 27; sepsis n = 29) were included and compared with healthy controls ( n = 18). SAA concentration was significantly increased in SIRS cats compared to controls, confirming its potential for the detection of systemic inflammation in this species. Significantly higher values of SAA were detected in cats belonging to the sepsis group; however, according to the results of the receiver operating characteristic curve analysis, the value of using SAA (>81 mg/L) to discriminate septic cats was only moderate (AUC = 0.76). Additionally, cats with sepsis had significantly higher serum bilirubin concentrations and toxic neutrophil changes compared to the trauma group. Overall, 38 of 56 cats were survivors; 18 of 56 were non-survivors, with 83% of the non-survivors (15 of 18) belonging to the sepsis group. Serum bilirubin concentration, but not SAA, was able to predict outcome. Prospective studies are needed to assess the potential of SAA in the diagnosis of feline sepsis and outcome prediction.
Taurolidine susceptibility of methicillin-resistant Staphylococcus pseudintermedius isolates
Authors: Wormhoudt Tiffany , Séguin Bernard , Bemis David A. , Hyatt Doreene
Published: July 2017

Infections caused by methicillin-resistant Staphylococcus pseudintermedius (MRSP) can be challenging to treat because they are often resistant to many other antimicrobial agents. We assessed the susceptibility of 29 MRSP isolates from dogs to taurolidine in vitro. There was no growth at 0.12% taurolidine and light growth at 0.06% for all isolates. Taurolidine was reliable at inhibiting growth of MRSP at a concentration of 1,200 µg/mL.
Participation of Racial and Ethnic Minorities in Technology-Based Interventions to Self-Manage Type 2 Diabetes: A Scoping Review
Authors: Jang Myoungock , Johnson Constance M. , D’Eramo-Melkus Gail , Vorderstrasse Allison A.
Published: July 2017

Purpose: Strategies to decrease societal and cultural barriers for ethnic minorities to participate in health research are well established. However, limited data are available regarding participation of ethnic minorities in mobile and Internet technology–based interventions to self-manage type 2 diabetes where health disparities are predominant. Thus, the purpose was to understand the participation of ethnic minorities in technology-based intervention programs to manage type 2 diabetes. Design/Method: A scoping review was used to review a total of 21 intervention studies containing participant information about ethnic minorities and one qualitative study discussing participation of ethnic minorities. Findings: There was limited enrollment and participation of ethnic minorities. Technological barriers in addition to existing societal and cultural barriers were identified. Strategies to decrease the barriers were recommended. Conclusions: Technological barriers were identified on top of the societal and cultural barriers in traditional interventions. Further research to reduce the barriers is warranted.
Design and mechanical testing of a variable stiffness morphing trailing edge flap
Authors: Ai Qing , Weaver Paul M , Azarpeyvand Mahdi
Published: July 2017

Morphing structures that are both lightweight and conformal to the aerofoil are currently being considered as promising candidates for the next generation of aircraft high-lift systems. Utilizing spatially variable stiffness materials in morphing structures leads to a possible reduction in the actuation energy requirement and also enables geometric control over the deformed shape of the morphing structure, resulting in enhanced aerodynamic and aeroacoustic performance. In this study, a design optimization methodology has been developed to identify the required material stiffness variations of a morphing structure for target optimal deformed shapes. In the optimization scheme, a layer-wise sandwich beam model is used to predict the structural behaviour of the flap with a specific material stiffness variation. Two-dimensional fluid/structure static aeroelastic interaction analysis is performed in the design optimization. Finite element analysis and mechanical tests were also carried out for a chosen optimization result to study the actuation requirements and the capability of control over the deformed shape of the morphing trailing edge. Numerical and experimental results confirm the feasibility of the proposed optimization methodology for identifying the required stiffness variation in the core and also ways of using rapid prototyped honeycomb core to realize the honeycomb core stiffness variations are discussed.
Longitudinal seismic response control of long-span cable-stayed bridges using shape memory alloy wire-based lead rubber bearings under near-fault records
Authors: Li Shuai , Dezfuli Farshad Hedayati , Wang Jing-quan , Alam M Shahria
Published: July 2017

This article investigates the efficiency of a new generation smart isolation system, namely shape memory alloy wire-based lead rubber bearing, for the seismic response control of long-span cable-stayed bridge systems under near-fault ground motions. The constitutive model of shape memory alloy wire-based lead rubber bearings is coded and implemented into OpenSees as a new user element. This user element can accurately predict the re-centering capability and energy dissipation capacity of shape memory alloy wire-based lead rubber bearing under different excitations. The Sutong cable-stayed bridge in China, with a main span of 1088 m, is taken as an example. Results reveal that implementing shape memory alloy wires into lead rubber bearings can effectively increase the self-centering property and, as a result, reduce the residual deformation in shape memory alloy wire-based lead rubber bearings under near-fault ground motions. Shape memory alloy wires lead to an increase in the horizontal stiffness and energy dissipation capacity of shape memory alloy wire-based lead rubber bearings. The deck displacement is restricted effectively, and a superior structural performance is achieved in terms of the deck acceleration. Shape memory alloy wire-based lead rubber bearings can effectively reduce the base shear and base moment of the towers. However, it is observed that an increase in the shape memory alloy wire diameter may have negligible effect on the deck acceleration, tower base shear and moment, and in some cases, on the pier base shear and moment.
Risk Assessments of Epidural Analgesia During Labor and Delivery
Authors: Herrera-Gómez Antonio , De Luna-Bertos Elvira , Ramos-Torrecillas Javier , Ocaña-Peinado Francisco M. , Ruiz Concepción , García-Martínez Olga
Published: July 2017

Epidural analgesia (EA) is one of the methods of choice for labor pain relief, but its adverse effects on the mother and child remain controversial. The objective of this study was to determine whether there is an association between the use of EA and different aspects of labor. The author(s) analyzed the effect of EA on different aspects of labor in a retrospective cohort observational study of deliveries in a public Spanish hospital during a 3-year period. Women with EA administration were found to increase the risk of stimulated labor, reduce the percentage of spontaneous deliveries, increase the risk of instrumental labor due to stalled labor or loss of fetal well-being, and increase the percentage of episiotomies. However, women with EA were not and increased risk for perineal laceration or the condition of the membranes at the delivery or with the type of placental expulsion. Thus, the administration of EA should be assessed in each case by the health care professional.
Procedures and Protocols for Weight Assessment During Acute Illness in Individuals With Anorexia Nervosa: A National Survey
Authors: Kelly-Weeder Susan , Kells Meredith , Jennings Karen , Dunne Julie , Wolfe Barbara
Published: July 2017

BACKGROUND: Weight assessment is a key component of nursing care for individuals with the acute illness of anorexia nervosa (AN). However, there is little data to guide protocols and procedures regarding weight assessment. OBJECTIVE: To describe institutional practices regarding weight assessment of individuals during acute illness of AN. DESIGN: Treatment facilities ( N = 24) completed a survey about written protocols and procedures regarding weight assessment and disclosure of weight to patients. RESULTS: The majority of facilities ( n = 22; 92%) have written protocols for weight assessment. Weight assessments occurred mostly in the morning ( n = 23; 95.8%), in hospital gowns ( n = 21; 87.5%), and after voiding ( n = 14; 58.3%). Respondents described mixed practices for disclosing weight to patients. CONCLUSION: Results indicate widespread variability in weight assessment and disclosure of weight. Further research is necessary to help develop evidence-based guidelines about weighing practices during acute illness for individuals with AN.
Using Virtual Patient Simulations to Prepare Primary Health Care Professionals to Conduct Substance Use and Mental Health Screening and Brief Intervention
Authors: Albright Glenn , Bryan Craig , Adam Cyrille , McMillan Jeremiah , Shockley Kristen
Published: July 2017

BACKGROUND: Primary health care professionals are in an excellent position to identify, screen, and conduct brief interventions for patients with mental health and substance use disorders. However, discomfort in initiating conversations about behavioral health, time concerns, lack of knowledge about screening tools, and treatment resources are barriers. OBJECTIVE: This study examines the impact of an online simulation where users practice role-playing with emotionally responsive virtual patients to learn motivational interviewing strategies to better manage screening, brief interventions, and referral conversations. DESIGN: Baseline data were collected from 227 participants who were then randomly assigned into the treatment or wait-list control groups. Treatment group participants then completed the simulation, postsimulation survey, and 3-month follow-up survey. RESULTS: Results showed significant increases in knowledge/skill to identify and engage in collaborative decision making with patients. CONCLUSIONS: Results strongly suggest that role-play simulation experiences can be an effective means of teaching screening and brief intervention.
The Milieu Manager: A Nursing Staffing Strategy to Reduce Observer Use in the Acute Psychiatric Inpatient Setting
Authors: Triplett Patrick , Dearholt Sandra , Cooper Mary , Herzke John , Johnson Erin , Parks Joyce , Sullivan Patricia , Taylor Karin F. , Rohde Judith
Published: July 2017

BACKGROUND: Rising acuity levels in inpatient settings have led to growing reliance on observers and increased the cost of care. OBJECTIVES: Minimizing use of observers, maintaining quality and safety of care, and improving bed access, without increasing cost. DESIGN: Nursing staff on two inpatient psychiatric units at an academic medical center pilot-tested the use of a “milieu manager” to address rising patient acuity and growing reliance on observers. Nursing cost, occupancy, discharge volume, unit closures, observer expense, and incremental nursing costs were tracked. Staff satisfaction and reported patient behavioral/safety events were assessed. RESULTS: The pilot initiatives ran for 8 months. Unit/bed closures fell to zero on both units. Occupancy, patient days, and discharges increased. Incremental nursing cost was offset by reduction in observer expense and by revenue from increases in occupancy and patient days. Staff work satisfaction improved and measures of patient safety were unchanged. CONCLUSIONS: The intervention was effective in reducing observation expense and improved occupancy and patient days while maintaining patient safety, representing a cost-effective and safe approach for management of acuity on inpatient psychiatric units.
Shake Your Stakeholder: Firms Leading Engagement to Cocreate Sustainable Value
Authors: Sulkowski Adam J. , Edwards Melissa , Freeman R. Edward
Published: July 2017

While most extant scholarship has focused on how stakeholders influence firms, we propose that firms play a critical role in “shaking” stakeholders. Shaking stakeholders means to proactively initiate cooperation with those affected by a firm to alter awareness, behavior, and networks so as to catalyze change in society and the marketplace to reward cocreated innovations in core operations of the firm that improve social and environmental impacts. Two previously underappreciated aspects of stakeholder relations are highlighted. First, the firm can be the entity that leads engagement that shakes stakeholders out of complacency. Second, firms can catalyze collaborative relationships to cocreate sustainable value that is shared with stakeholders. We offer several cases to illustrate this strategy. While stakeholder shaking may be useful in any business environment, global ecological crises, societal problems, and governance failures heighten the need for firms to take action to bring about profound and systemic changes.
Preparing elementary readers to be critical intercultural citizens through literacy education
Authors: Huh Seonmin , Suh Young-Mee
Published: July 2017

The purpose of this study is to extend existing approaches to civic and English as a foreign language (EFL) literacy education to include critical intercultural citizenship. Students not only need to learn how to communicate, but should also develop their positions as citizens who exercise literacy skills to demonstrate connections to others in intercultural domains. The central research question explored how teacher pedagogy in the intercultural citizenship curriculum helped students to become more intercultural and caring citizens. A practitioner action study was conducted for two years with 10 fifth- and sixth-graders (11–12 years old) in Korea. All 40 one-hour video-taped class sessions containing eleven graphic novel discussions, as well as the artifacts students produced, were collected for analysis. Data analysis illustrates that critical citizenship literacy skills can be developed with teacher pedagogy that help students reflect on the cultural knowledge and practices that seem natural to them. The pedagogies of dialoguing, active consideration of missing perspectives and direct juxtaposition of students’ own and others’ social contexts are unpacked to suggest ways of incorporating intercultural citizenship education into literacy education. Educational implications are considered in terms of teacher engagement with learners, expanded position-taking of learners as intercultural citizens, and selection of discussion topics.
The role of emotions and positionality in the trajectories of ‘new speakers’ of Irish
Authors: Walsh John
Published: July 2017

Aims and Objectives/Purpose/Research Questions:

The aim of this paper is to describe and analyse the emotional experiences and positionality of ‘new speakers’ of Irish, fluent and regular speakers who were not raised with Irish in the historical Irish-speaking heartland known as the Gaeltacht. The role of emotions in facilitating the transition to new speakerhood is considered, as is their influence on the speakers’ continued use of Irish and on their positionality in relation to other speakers.

Design/Methodology/Approach:

The paper is based on semi-structured narrative interviews conducted with participants identified as active and competent new speakers of Irish. It is part of a larger European project on the topic of new speakers.

Data and Analysis:

The sample size is 46 interviews from a database of 100 Irish speakers and was analysed using NVivo qualitative analysis.

Findings/Conclusions:

Becoming a new speaker of Irish is a deeply emotional process, both before and after the transition, as subjects grapple with additional obstacles to acquisition and use due to the language’s minoritised status. The emotions involved in adopting a minoritised language such as Irish appear to be qualitatively different from other languages because of the additional obstacles involved in mastering a language with a weak sociolinguistic profile.

Originality:

The paper’s originality stems from the fact that it is the first systematic study of emotions and positionality among new speakers of Irish and is distinct from existing quantitative studies of language attitudes. An additional innovation is its theoretical framework which aims to guide understanding of emotions and positionality among new speakers of minoritised languages in particular rather than majority languages in general.

Significance/Implications:

The paper is theoretically significant because existing work on language and emotions has not focused on minoritised languages. Significance attaches to the related finding that the emotional process is not the same for minoritised languages and other more dominant languages.
Sport and feminism in China: On the possibilities of conceiving roller derby as a feminist intervention
Authors: Pavlidis Adele , O’Brien Wendy
Published: July 2017

The spread of contemporary roller derby presents an opportunity to examine the ways sport can act as a form of feminist intervention. This article draws on a qualitative case study of a roller derby league in China, made up predominantly of expatriate workers, to explore some of the possibilities roller derby presents in activating glocal forms of feminist participatory action. The globalization of sport has often been associated with colonialism and the loss of local physical cultures, together with commercialization. Roller derby provides a very different case, where, together with the spread of the game, comes a focus on gender diversity, female strength and a particular derby style of DIY (do-it-yourself) governance that may support forms of participatory action. As an exploratory study, this article points towards the potential of roller derby, and possibly other sport cultures, to support human rights activism in the Asia Pacific.
Technique selection and evaluation of ballast water management methods under an intuitionistic fuzzy environment: An information axiom approach
Authors: Kuroshi Lawrence , Ölçer Aykut
Published: July 2017

A recent survey showed the reluctance of ship-owners to install ballast water treatment systems onboard their ships. This raised a question on the acceptability of shipboard management of ballast water and the need to investigate the potential of non-shipboard alternatives to managing the menace of invasive species transfer via ships’ ballast water. The aim of this article is to investigate the viability of both shipboard and onshore-based concepts of ballast water management with respect to the evaluation criteria stipulated in the Ballast Water Management Convention of the International Maritime Organization. To achieve that, an appropriate decision-making technique was selected using a robust procedure; this is critical in the evaluation and ultimate selection of an appropriate ballast water management method. A multi-criteria decision-making technique known as intuitionistic fuzzy multi-attribute axiomatic design which is a hybridized extension of fuzzy axiomatic design was employed for the selection process. The eventual selected technique was used to evaluate the ballast water management options based on the linguistic data collected from an interview with ballast water management experts. The novel applications of intuitionistic fuzzy multi-attribute axiomatic design in this article for technique selection and subsequently for ballast water management methods’ evaluation exemplify not only the versatility of the technique as a decision-making tool but also showed a strong paradigm shift in experts’ opinions about the future of ballast water management beyond just the traditional shipboard system.
The development of a model for determining scheduled replacement intervals for marine machinery systems
Authors: Emovon Ikuobase , Norman Rosemary A , Murphy Alan J
Published: July 2017

One of the challenges of maintenance management of a marine machinery system is the problem of selecting the optimum interval for replacement of equipment items. Most of the approaches that are given in the literature for selecting optimum replacement intervals are based on a single criterion model such as cost. This approach may be satisfactory for some industries but for the marine industry disruption in services will result in a considerable cost penalty and, as such, other factors such as system downtime and system reliability must be taken into consideration when determining the optimum replacement interval for the system. These decision criteria have been proven to be in conflict with one another. On this basis, a multi-criteria decision-making tool, Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS), is proposed in this article for aggregating multiple criteria in order for them to be used simultaneously in determining the optimum scheduled replacement interval for the equipment items of the system. The use of a multi-criteria decision-making tool allows the decision-maker to express preference for the decision criteria in terms of their levels of importance. To achieve this aim, a compromise decision weighting technique is integrated with TOPSIS. The compromise weighting technique was obtained from a combination of the variance method (an objective decision criteria weighting technique) and analytical hierarchy process (a subjective decision criteria weighting technique). In order to demonstrate the applicability of the proposed innovative methodology for determining the optimum replacement intervals for a marine machinery system and also validate the technique, a case study involving some equipment items of a marine diesel engine is presented. Although results show that it produces the same optimum solution as the methods in the literature, the proposed method is more flexible and less computationally intensive.
A low cost autonomous underwater vehicle for patrolling and monitoring
Authors: Allotta Benedetto , Conti Roberto , Costanzi Riccardo , Fanelli Francesco , Gelli Jonathan , Meli Enrico , Monni Niccolò , Ridolfi Alessandro , Rindi Andrea
Published: July 2017

The involvement of autonomous underwater vehicles for patrolling, monitoring or maintenance activities of submersed structures in the coastal strip, harbors or in proximity of off-shore plants (e.g. in oil& gas and military fields), can represent a high benefit for the economy of the related areas. For instance, continuous or more frequent monitoring can be possible, with a reduction of the necessary costs: The use of remotely operated vehicles with the linked implication of support ships and specialized pilots, or the involvement of professional divers, could be avoided or significantly reduced. The paper describes the FeelHippo autonomous underwater vehicles, the vehicle designed and built by the MDM Lab of the University of Florence; it is a low cost autonomous underwater vehicles suitable for these purposes. In particular, an onboard acoustic localization system, based on a low cost approach, has been implemented and preliminary experimental results are here reported.
An autonomous underwater vehicle positioning matching method based on iterative closest contour point algorithm and affine transformation
Authors: Zhang Tao , Li Yao , Tong Jinwu
Published: July 2017

An improved autonomous underwater vehicle federal integrated navigation method based on two-stage position matching technology is proposed in this study to solve the problem of positioning divergence caused by the defects of error accumulation in an inertial navigation system. The improved two-stage position matching method includes the acquisition and preprocessing of the strap-down inertial navigation system and indicates track sequences and elevation measurement sequences. The first-stage position matching is based on iterative closest contour point, while the second-stage position matching is based on an affine algorithm. Simulation results indicate that the proposed algorithm solves the problem of the limitation of the rigid transformation of traditional iterative closest contour point and effectively resolves the matching failure caused by the large initial position error of long-time navigation.
Distributed robust H∞ composite-rotating consensus of second-order multi-agent systems
Authors: Huang Weizheng , Zheng Wenfeng , Mo Lipo
Published: July 2017

In this article, the distributed [Formula: see text] composite-rotating consensus problem is concerned for a class of second-order multi-agent systems. First, based on local state feedback and communication feedback, a distributed control algorithm is proposed. Then, sufficient conditions are derived in order to make all agents reach a composite-rotating consensus with the desired [Formula: see text] performance. Finally, the simulations are given to show the effectiveness of the theoretical results.
Physical control framework and protocol design for cyber-physical control system
Authors: Cai Yi , Qi Deyu
Published: July 2017

A cyber-physical system is an integration of computation, networking, and physical processes. This article introduces a novel physical control framework to integrate various devices to form the lower-level abstraction network. Two relevant protocols within this framework are proposed for information exchange between different network environments. Furthermore, a formal verification method for the proposed protocols is discussed. The model-checking tool SPIN is used to model and formally verify such protocols. The properties of the protocols are expressed using linear temporal logic to enable model-checking. Implementation results are presented to provide a deeper understanding of the proposed protocols.
Dynamic change of transcription pausing through modulating NELF protein stability regulates granulocytic differentiation
Authors: Liu Xiuli , Gogate Aishwarya A. , Tastemel Melodi , Malladi Venkat S. , Yao Huiyu , Nguyen Kim , Huang Lily Jun-Shen , Bai Xiaoying
Published: July 2017

Key Points

Granulocytic differentiation triggers a decrease of NELF protein abundance. Downregulation of NELF-mediated transcription pausing is necessary and sufficient for granulocytic differentiation.
Validity and reliability of grade scoring in the diagnosis of exercise-induced laryngeal obstruction
Authors: Walsted Emil Schwarz , Hull James H. , Hvedstrup Jeppe , Maat Robert Christiaan , Backer Vibeke
Published: July 2017

The current gold-standard method for diagnosing exercise-induced laryngeal obstruction (EILO) is continuous laryngoscopy during exercise (CLE), with severity classified by a visual grade scoring system. We evaluated the precision of this approach, by evaluating test–retest reliability of CLE and both inter- and intra-rater variability.

In this prospective case–control study, subjects completed four consecutive treadmill CLE tests under identical conditions. Laryngoscopic video recordings were anonymised and graded by three expert raters. 2 months following initial scoring, videos were re-randomised and rating repeated to assess intra-rater agreement.

20 subjects (16 cases and four controls) completed four CLE tests. The time to exhaustion increased by 30 s (95% CI 0.02–57.8, p<0.05) in the second CLE compared with the first test, but remained identical in the subsequent tests. Only one-third of subjects retained their initial diagnosis in the subsequent three tests. Inter-rater agreement on grade scores (weighted Cohen's ϰ) was 0.16–0.45, while intra-rater agreement ranged from 0.30 to 0.67.

The CLE test is key in the diagnostic assessment of patients with EILO. However, the widely adopted visual grade scoring system does not appear to be a robust means for reliably classifying severity of EILO.
Skin in the game: the use of sensing smart fabrics in tennis costume as a means of analyzing performance
Authors: Chittenden Tara
Published: July 2017

Underlying the surface decoration and cut of contemporary tennis costume is a fabric that enacts its own performance and studies the athlete who wears it. Whilst designers such as Teddy Tinling created tennis costumes that brought glamour and theatrical flair to the player’s performance, modern sports companies are increasingly using costume to approach human performance from a big data perspective. In the late nineteenth century, women playing tennis wore corsets and long skirts which impeded movement; today, the top players utilize fabric science that enables costume to control and record the temperature, sweat and muscle movement of the performer, whilst also presenting a vehicle to showcase their personality through their aesthetic choices. Smart fabrics allow for greater and more precise control over how our bodies perform, and they similarly alter our understanding of materiality and bodily presence with regards to fashion. The use of smart fabrics in sports, where the patterns of data collected by the costume visually and numerically display the conditions of the player/performance, holds potential for the ways in which we interrogate the interrelationship of clothing and performance across a range of arenas. For fashion research this means it is now possible not just to look at a costume but to look through it, via biometric capture, to a performance realized in data space. It is this duality of costume both in and as performance space that provokes this article to raise questions about the changeable nature of smart clothing and its relationship to the sporting body.
The nonreceptor protein tyrosine kinase Pyk2 promotes the turnover of monocytes at steady state
Authors: Llewellyn Ryan A , Thomas Keena S , Gutknecht Michael F , Bouton Amy H
Published: July 2017

Monocytes are short-lived myeloid cells that perform functions essential for tissue homeostasis and disease resolution. However, the cellular mechanisms controlling the maintenance and turnover of monocyte populations are largely undefined. Proline-rich tyrosine kinase 2 (Pyk2) is a nonreceptor tyrosine kinase that regulates numerous immune cell functions, but its role in monocytes is currently unknown. In this study, we sought to characterize the expression and function of Pyk2 in lineage-committed monocyte populations. Here, we report that Pyk2 protein expression is increased in the Ly6C− monocyte population. Using a Pyk2 knockout mouse model (Pyk2−/−), we show that Pyk2 regulates the relative proportion of monocyte subsets normally represented in the bone marrow (BM) at steady state. In support of this conclusion, a similar phenotype was observed in the peripheral blood and spleen. Data from reciprocal BM chimera experiments indicate that the alterations in monocyte populations exhibited by Pyk2−/− mice are due to factors intrinsic to the monocytes. Lineage-tracing of monocyte populations suggests that Pyk2 promotes apoptosis in BM monocytes, thereby acting as an important homeostatic regulator of turnover in these short-lived, innate immune cells.
Frontline Science: CXCR7 mediates CD14+CD16+ monocyte transmigration across the blood brain barrier: a potential therapeutic target for NeuroAIDS
Authors: Veenstra Mike , Williams Dionna W , Calderon Tina M , Anastos Kathryn , Morgello Susan , Berman Joan W
Published: July 2017

CD14+CD16+ monocytes transmigrate into the CNS of HIV-positive people in response to chemokines elevated in the brains of infected individuals, including CXCL12. Entry of these cells leads to viral reservoirs, neuroinflammation, and neuronal damage. These may eventually lead to HIV-associated neurocognitive disorders. Although antiretroviral therapy (ART) has significantly improved the lives of HIV-infected people, the prevalence of cognitive deficits remains unchanged despite ART, still affecting >50% of infected individuals. There are no therapies to reduce these deficits or to prevent CNS entry of CD14+CD16+ monocytes. The goal of this study was to determine whether CXCR7, a receptor for CXCL12, is expressed on CD14+CD16+ monocytes and whether a small molecule CXCR7 antagonist (CCX771) can prevent CD14+CD16+ monocyte transmigration into the CNS. We showed for the first time that CXCR7 is on CD14+CD16+ monocytes and that it may be a therapeutic target to reduce their entry into the brain. We demonstrated that CD14+CD16+ monocytes and not the more abundant CD14+CD16− monocytes or T cells transmigrate to low homeostatic levels of CXCL12. This may be a result of increased CXCR7 on CD14+CD16+ monocytes. We showed that CCX771 reduced transmigration of CD14+CD16+ monocytes but not of CD14+CD16− monocytes from uninfected and HIV-infected individuals and that it reduced CXCL12-mediated chemotaxis of CD14+CD16+ monocytes. We propose that CXCR7 is a therapeutic target on CD14+CD16+ monocytes to limit their CNS entry, thereby reducing neuroinflammation, neuronal damage, and HIV-associated neurocognitive disorders. Our data also suggest that CCX771 may reduce CD14+CD16+ monocyte-mediated inflammation in other disorders.
p53-independent DUX4 pathology
Authors: Bosnakovski Darko , Gearhart Micah D. , Toso Erik A. , Recht Olivia O. , Cucak Anja , Jain Abhinav K. , Barton Michelle C. , Kyba Michael
Published: July 2017

FSHD is a genetically dominant myopathy caused by mutations that disrupt repression of the normally silent DUX4 gene, which encodes a transcription factor that has been shown to interfere with myogenesis when misexpressed at very low levels in myoblasts, and to cause cell death when overexpressed at high levels. A previous report using adeno-associated virus to deliver high levels of DUX4 to mouse skeletal muscle demonstrated severe pathology that was suppressed on a p53 knockout background, implying that DUX4 acted through the p53 pathway. Here, we investigate the p53-dependence of DUX4 using various in vitro and in vivo models. We find that inhibiting p53 has no effect on the cytoxicity of DUX4 on C2C12 myoblasts, and that expression of DUX4 does not lead to activation of the p53 pathway. DUX4 does lead to expression of the classic p53 target gene, Cdkn1a (p21), however in a p53-independent manner. Meta analysis of 5 publicly available data sets of DUX4 transcriptional profiles in both human and mouse cells shows no evidence of p53 activation, and further reveals that Cdkn1a is a mouse-specific target of DUX4. When the inducible DUX4 mouse model is crossed onto the p53 null background, we find no suppression of the male-specific lethality or skin phenotypes that are characteristic of the DUX4 transgene, and find that primary myoblasts from this mouse are still killed by DUX4 expression. These data challenge the notion that the p53 pathway is central to the pathogenicity of DUX4.
The chromatin remodeling BAP complex limits tumor promoting activity of the Hippo pathway effector Yki to prevent neoplastic transformation inDrosophilaepithelia
Authors: Song Shilin , Herranz Héctor , Cohen Stephen M.
Published: July 2017

SWI/SNF chromatin remodeling complexes are mutated in many human cancers. In this report we make use of a Drosophila genetic model for epithelial tumor formation to explore the tumor suppressive role of SWI/SNF complex proteins. Members of the BAP complex exhibit tumor suppressor activity in tissue overexpressing the Yorkie (Yki) proto-oncogene, but not in tissue overexpressing EGFR. The BAP complex has been reported to serve as a Yki-binding cofactor to support Yki target expression. However, we observed that depletion of BAP leads to ectopic expression of Yki targets both autonomously and non-autonomously, suggesting additional indirect effects. We provide evidence that BAP complex depletion causes upregulation of the Wingless and Dpp morphogens to promote tumor formation in cooperation with Yki.
L-leucyl-L-leucine methyl ester does not release cysteine cathepsins to the cytosol but inactivates them in transiently permeabilized lysosomes
Authors: Repnik Urska , Borg Distefano Marita , Speth Martin Tobias , Ng Matthew Yoke Wui , Progida Cinzia , Hoflack Bernard , Gruenberg Jean , Griffiths Gareth
Published: July 2017

L-leucyl-L-leucine methyl ester (LLOMe) induces apoptosis, which is thought to be mediated by release of lysosomal cysteine cathepsins from permeabilized lysosomes into the cytosol. Here, we demonstrated in HeLa cells that apoptotic as well as sub-apoptotic concentrations of LLOMe caused rapid and complete lysosomal membrane permeabilization (LMP), as evidenced by loss of the proton gradient and release into the cytosol of internalized lysosomal markers below a relative molecular mass of 10,000. However, there was no evidence for the release of cysteine cathepsins B and L into the cytosol; rather they remained within lysosomes, where they were rapidly inactivated and degraded. LLOMe-induced adverse effects, including LMP, loss of cysteine cathepsin activity, caspase activation and cell death could be reduced by inhibition of cathepsin C, but not by inhibiting cathepsins B and L. When incubated with sub-apoptotic LLOMe concentrations, lysosomes transiently lost protons but annealed and re-acidified within hours. Full lysosomal function required new protein synthesis of cysteine cathepsins and other hydrolyses. Our data argue against the release of lysosomal enzymes into the cytosol and their proposed proteolytic signaling during LLOMe-induced apoptosis.
Ezrin directly interacts with AQP2 and promotes its endocytosis
Authors: Li Wei , Jin William W. , Tsuji Kenji , Chen Ying , Nomura Naohiro , Su Limin , Yui Naofumi , Arthur Julian , Cotecchia Susanna , Păunescu Teodor G. , Brown Dennis , Lu Hua A. J.
Published: July 2017

The water channel aquaporin-2 (AQP2) is a major regulator of water homeostasis in response to vasopressin (VP). Dynamic trafficking of AQP2 relies on its close interaction with trafficking machinery proteins and the actin cytoskeleton. Here, we report the identification of ezrin, an actin-binding protein from the ezrin/radixin/moesin (ERM) family as an AQP2-interacting protein. Ezrin was first detected in a co-immunoprecipitation (co-IP) complex using an anti-AQP2 antibody in a proteomic analysis. Immunofluorescence staining revealed the co-expression of ezrin and AQP2 in collecting duct principal cells, and VP treatment caused redistribution of both proteins to the apical membrane. The ezrin–AQP2 interaction was confirmed by co-IP experiments with an anti-ezrin antibody, and by pulldown assays using purified full-length and FERM domain-containing recombinant ezrin. By using purified recombinant proteins, we showed that ezrin directly interacts with AQP2 C-terminus through its N-terminal FERM domain. Knocking down ezrin expression with shRNA resulted in increased membrane accumulation of AQP2 and reduced AQP2 endocytosis. Therefore, through direct interaction with AQP2, ezrin facilitates AQP2 endocytosis, thus linking the dynamic actin cytoskeleton network with AQP2 trafficking.
Cells lay their own tracks – optogenetic Cdc42 activation stimulates fibronectin deposition supporting directed migration
Authors: Zimmerman Seth P. , Asokan Sreeja B. , Kuhlman Brian , Bear James E.
Published: July 2017

Rho GTPase family members are known regulators of directed migration and therefore play key roles in processes including development, the immune response and cancer metastasis. However, their individual contributions to these processes are complex. Here, we modify the activity of the two Rho GTPase family members Rac and Cdc42 by optogenetically recruiting specific guanine nucleotide exchange factor (GEF) DH or PH domains to defined regions of the cell membrane. We find that the localized activation of both GTPases produces lamellipodia in cells plated on a fibronectin substrate. By using a novel optotaxis assay, we show that biased activation can drive directional migration. Interestingly, in the absence of exogenous fibronectin, Rac activation is insufficient to produce stable lamellipodia or directional migration whereas Cdc42 activation is sufficient for these processes. We find that a remarkably small amount of fibronectin (<10 puncta per protrusion) is necessary to support stable GTPase-driven lamellipodia formation. Cdc42 bypasses the need for exogenous fibronectin by stimulating cellular fibronectin deposition under the newly formed lamellipodia.

This article has an associated First Person interview with the first author of the paper.
TRIM65 triggers β-catenin signaling via ubiquitylation of Axin1 to promote hepatocellular carcinoma
Authors: Yang Yu-Feng , Zhang Mei-Fang , Tian Qiu-Hong , Zhang Chris Zhiyi
Published: July 2017

Deregulation of ubiquitin ligases contributes to the malignant progression of human cancers. Tripartite motif-containing protein 65 (TRIM65) is an E3 ubiquitin ligase and has been implicated in human diseases, but its role and clinical significance in hepatocellular carcinoma (HCC) remain unknown. Here, we showed that TRIM65 expression was increased in HCC tissues and associated with poor outcome in two independent cohorts containing 888 patients. In vitro and in vivo data demonstrated that overexpression of TRIM65 promoted cell growth and tumor metastasis, whereas knockdown of TRIM65 resulted in opposite phenotypes. Further studies revealed that TRIM65 exerted oncogenic activities via ubiquitylation of Axin1 to activate the β-catenin signaling pathway. TRIM65 directly bound to Axin1 and accelerated its degradation through ubiquitylation. Furthermore, HMGA1 was identified as an upstream regulator of TRIM65 in HCC cells. In clinical samples, TRIM65 expression was positively correlated with the expression of HMGA1 and nuclear β-catenin. Collectively, our data indicate that TRIM65 functions as an oncogene in HCC. The newly identified HMGA1/TRIM65/β-catenin axis serves as a promising prognostic factor and therapeutic target.
Engineering mammalian cells to seek senescence-associated secretory phenotypes
Authors: Qudrat Anam , Wong Janice , Truong Kevin
Published: July 2017

Since the removal of senescent cells in model organisms has been linked to rejuvenation and increased lifespan, senotherapies have emerged to target senescent cells for death. In particular, interleukin-6 (IL6) is a prominent senescence-associated secretory phenotype (SASP) and, thus, seeking IL6 could potentially localize engineered cells to senescent cells for therapeutic intervention. Here, we engineered a chimeric IL6 receptor (IL6Rchi) that generates a Ca2+ signal in response to IL6 stimulation. When IL6Rchi was co-expressed with an engineered Ca2+-activated RhoA (CaRQ), it enabled directed migration to IL6 in cells that have no such natural ability. Next, the removal of target cells was accomplished by the mechanism of membrane fusion and subsequent death. This work represents a first step towards engineering a cell to target senescent cells that secrete high levels of IL6. For increased specificity to senescent cells, it will likely be necessary for an engineered cell to recognize multiple SASPs simultaneously.
Role of outstretched fore legs of flying beetles revealed and demonstrated by remote leg stimulation in free flight
Authors: Li Yao , Cao Feng , Vo Doan Tat Thang , Sato Hirotaka
Published: July 2017

In flight, many insects fold their forelegs tightly close to the body, which naturally decreases drag or air resistance. However, flying beetles stretch out their forelegs for some reason. Why do they adopt this posture in flight? Here, we show the role of the stretched forelegs in beetle Mecynorrhina torquata flight. Using leg motion tracking and electromyography in flight, we found that the forelegs were voluntarily swung clockwise in yaw to induce counter-clockwise rotation of the body for turning left, and vice versa. Furthermore, we demonstrated remote control of left-right turnings in flight by swinging the forelegs via a remote electrical stimulator for the leg muscles. The results and demonstration reveal that the beetle's forelegs play a supplemental role in directional steering during flight.
Changes of loggerhead turtle (Caretta caretta) dive behavior associated with tropical storm passage during the inter-nesting period
Authors: Wilson Maria , Tucker Anton D. , Beedholm Kristian , Mann David A.
Published: July 2017

To improve conservation strategies for threatened sea turtles more knowledge on their ecology, behavior, and how they cope with severe and changing weather conditions is needed. Satellite and animal motion datalogging tags were used to study the inter-nesting behavior of two female loggerhead turtles in the Gulf of Mexico, which regularly has hurricanes and tropical storms during nesting season. We contrast the behavioral patterns and swimming energetics of two turtles, the first tracked in calm weather and a second tracked before, during, and after a tropical storm. Turtle #1 was highly active and swam at the surface or submerged 95% of the time during the entire inter-nesting period with high estimated specific oxygen consumption rate (0.95 ml min−1 kg−0.83). Turtle #2 was inactive for most of the first nine days of the inter-nesting period where she rested at the bottom (80% of the time) with low estimated oxygen consumption (0.62 ml min−1 kg−0.83). Midway through the inter-nesting period turtle #2 encountered a tropical storm and became highly active (swimming 88% of the time during and 95% after the storm). Her oxygen consumption increased significantly to 0.97 ml min−1 kg−0.83 during and 0.98 ml min−1 kg−0.83 after the storm. However, despite of the tropical storm turtle #2 returned to the nesting beach, where she successfully re-nested 75 meters from her previous nest. Thus, the tropical storm had a minor effect on this female's individual nesting success, even though the storm caused 90% loss of Casey Key nests.
The season of mellow data
Authors: Allingham Sue
Published: July 2017

While we wait for the latest Early Years Foundation Stage Profile results and with summer upon us, it is important we keep abreast of what is being said nationally – we must be informed and proactive.
Letters
Authors: McVay Sue , Tanuku Purnima , Leitch Neil
Published: July 2017

MA Education Ltd, St Jude's Church, Dulwich Road, London, SE24 0PB neil.henty@markallengroup.com
Reflections on what school readiness really means
Authors: Lee Maureen
Published: July 2017

A focus on what ‘being ready for school’ means for both schools and children when they take those important steps between different settings is an increasingly vital part of training for early years teachers.
We need to take care of ourselves to help children
Authors: Mainstone-Cotton Sonia
Published: July 2017

Last month, I explored how we can use outdoor and sensory play, and emotion language, to enhance wellbeing. In this article, I offer further ideas, exploring how our own mental health impacts on children.
Play and staff autonomy coming under pressure
Authors: Campbell-Barr Verity
Published: July 2017

This series on international perspectives of ECEC is designed to offer a window into what is happening in other countries in the hope of fostering a process of reflection. This month, early years in Hungary.
On the contrary: the role played by opposing ideas
Authors: Brown Paula
Published: July 2017

The concepts formed by using binary opposites, such as good/evil, form a fundamental part of our thinking. In this article, we review how we can use them to enhance young children's learning.
Stereotypes are being written out of the script
Authors: Francis-Pester Dawn
Published: July 2017

Books play an important part of any home or early years setting, helping to shape a child's nascent understanding of the world around them, especially in terms of gender equality and diversity.
Offering more when the pot is dry
Authors: Neagle Jackie
Published: July 2017

Want to know the real impact of the government's continued underfunding of its childcare entitlement for parents? Despite claims that all is well with the 30-hour offer, nurseries are now beginning to close.