bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategic Options for Forestry Development in Asian-Pacific Countries
Authors: Mok S.T.
Published: January 2017

Asian-Pacific is ecologically and economically diverse, but, the countries within it have some common features. Generally, rapid depletion of fuelwood, timber harvesting and human settlements have caused serious environmental degradation. Sustainable forest management and development based on a conservational approach is probably the most realistic solution. Regional cooperation should be encouraged to develop strategic options and appropriate technologies, skills, and information required for effective forest resources conservation.
A general classification of U-shaped dose-response relationships in toxicology and their mechanistic foundations
Authors: Calabrese Edward J , Baldwin Linda A
Published: January 2017

The development of a comprehensive database of chemical hormetic responses (i.e., U-or inverted U-shaped dose-response relationships) using objective a priori study design, statistical and study replication criteria has recently been reported.1 An assessment of this database reveals the existence of a wide range of hormetic dose-reponse relationships including those demonstrating a direct stimulation or an overcompensation response to a disruption of homeostasis. These two broad types of hormetic responses are affected by temporal factors and display unique patterns of dose-range stimulation, magnitude of stimulatory response and relationship of the maximum stimulatory response to the NOAEL. A general classification of U-shaped dose-response relationships is proposed to provide a more organized framework to evaluate the highly distinctive and diverse hormetic responses within the context of establishing underlying biological mechanisms and exploring risk assessment implications.
Castration prevents calcium channel blocker-induced gingival hyperplasia in beagle dogs
Authors: Dayan Dan , Kozlovsky Avital , Tal Haim , Kariv Noam , Shemesh Mordechai , Nyska Abraham
Published: January 2017

1 The purpose of this study was to investigate testosterone's role on the calcium channel antagonist oxodi-pine-inducing gingival hyperplasia in a dog model.

2 Two experiments were conducted using castrated and intact male dogs. Oxodipine was administered orally for 90 days, at a dose of 24 mg/kg/day. In the first experiment, the occurrence of gingival hyperplasia was evaluated. In the second, the gingival index (GI) and gingival hyperplasia index (GHI) were recorded and correlated with serum levels of testosterone.

3 A significant positive correlation between GI, GHI and plasma testosterone was noted. Castrated dogs were injected with testosterone, 4 months after the start of oxodipine treatment, while in the non-castrated dogs, administration of oxodipine was stopped. Castration correlated with lack of GH, while testosterone injection to the same dogs was associated with an increase of GI and GHI.

4 Since it is known that testosterone receptors are present in the gingiva, it is proposed that oxodipine-induced gingival hyperplasia could be mediated by the calcium channel blocker on plasma testosterone levels.
The role of non-corticosteroid related factors in osteonecrosis (ON) in systemic lupus erythematosus: a nested case-control study of inception patients
Authors: Prasad R , Ibanez D , Gladman D , Urowitz M
Published: January 2017

Several factors have been associated with the development of osteonecrosis (ON) in SLE but corticosteroid (CS) therapy has been the most consistent association. We sought to determine factors that predisposed to, or protected from, the development of ON in lupus patients when cumulative oral corticosteroid doses were matched between cases and controls, thereby removing presence of corticosteroid therapy and cumulative dose as risk factors. A nested case-control study of an inception cohort of SLE patients was used to determine the clinical, laboratory and therapeutic differences between patients who developed their first ON event and patients who did not develop ON, having matched these groups for their cumulative oral corticosteroid doses. Of the 570 patients seen within the first year after diagnosis 65 (11.4%) developed ON. None of the variables examined were found to confer additional ON risk in multivariate analysis. It appears that the major factor associated with the development of ON is corticosteroid therapy. Factors which may protect a majority of patients on corticosteroids from developing ON remain to be elucidated.
Perfectionism: Its Measurement and Career Relevance
Authors: Slaney Robert B. , Ashby Jeffrey S. , Trippi Joseph
Published: January 2017

The meaning and measurement of the construct of perfectionism has potentially important implications for career choice and career development. The present article reviews the theoretical and empirical background of perfectionism. It then discusses the scales previously developed to measure perfectionism and describes the development of a new scale, the Almost Perfect Scale (APS; Slaney & Johnson, 1992). Two additional studies are presented on the APS. The first consists of three parts that examine the concurrent validity of the APS and the factor structure of the subscales of the APS relative to the subscales of two other scales developed to measure perfectionism. The second study examines the factor structure of the APS through the use of a confirmatory factor analysis. The results are discussed and suggestions are made for future research that would study the relationship between perfectionism and a variety of career variables.
‘Welcome to the whiteboard, the new member of the team’: Identity regulation as a sociomaterial process
Authors: Paring Géraldine , Pezé Stéphan , Huault Isabelle
Published: January 2017

Organizations are frequently subject to changes that promote new and/or (supposedly) trendy identities for their members. Various studies have sought to understand how such identity regulation processes are achieved through discourse, a fact that has led researchers to call for a more material understanding of this phenomenon. Through an in-depth ethnography of a transformation programme aimed at constructing a new social identity among project managers – that of internal consultant – we find that identity regulation is exercised through a sociomaterial process affording the performativity of the promoted identity, mainly through the consultants’ bodily performances. This is important because it shows how identity regulation is achieved through both (and intertwined) discourse and materiality.
Experimental investigation of cage motions in an angular contact ball bearing
Authors: Wen Baogang , Ren Hongjun , Zhang Hao , Han Qingkai
Published: January 2017

The commonly known effects of both the rotating speeds and external loads on the bearing dynamics or life behaviors are mostly caused by its cage dynamics, because of the complicated contact and collision interactions between the cage and other parts such as the inner or outer rings and balls. In this paper, experimental investigation of dynamic motions of a cage is carried out under various rotating speeds and external loads in a ball bearing. On a bearing test rig, the cage motions in axial and radial directions are measured by use of eddy transducers installed inside the bearing house and the subpanel. Then the measured results are analyzed by fast Fourier transform and compared at different operating conditions including rotating speeds, axial and radial forces, or moments. The three-dimensional space motions of the cage are also constructed to illustrate its different modes. Results reveal that the cage motions are typically periodic in the three directions. The motion frequencies consist of the cage rotating frequency and its multi-frequency, the inner ring rotating frequency, and also some combination frequencies of the cage and inner ring. The obtained characteristic frequencies of the cage motion in axial are similar to that in radial, but different in the variety of amplitudes under the same operating conditions. The increment of rotating speeds and axial loads of the bearing gradually make the whirl trajectories of the cage mass center regular, and enlarge its whirl radii. Instead, the whirl trajectories change from well-defined patterns to complicated ones, and its whirl radii decrease on increasing the radial loads and moments of the bearing. All the obtained experimental results are useful references for dynamic design and life prediction of high-speed and low-load bearings commonly used in many machines.
The Place of ‘Childhood’ in Internet Content Regulation
Authors: Oswell David
Published: January 2017

This paper discusses recent policy calculations in the UK concerning the Internet and child protection issues. Through an analysis of official documents, conference presentations, interviews and press reports, a story is pieced together of the culture of policy making. Problems are made visible, social agents mobilized and techniques invented for the enactment of policy. Central to my argument is an analysis of how childhood is figured discursively as a particular problem for regulation. Policy decisions are made, not in relation to ‘real’ children, but in relation to their representation and the authority of those who claim to represent them. I focus specifically on the circulation of three images of the child: the child-as-victim, the child-in-danger and the dangerous child.
The Voice from the Void
Authors: Sconce Jeffrey
Published: January 2017

This piece examines the proliferation of paranormal discourses around wireless and radio in the early decades of the century. Engaging popular fiction and parapsychological literature of the era, the article gives particular emphasis to the period's reigning image of ‘the etheric ocean’, discussing the symbolic importance of this metaphor in stories casting radio as a medium of the dead and of telepathy. Linking these often sinister stories to the vast social transformations of modernity, the article argues that the generally enthusiastic reception of the new medium was tempered by these occult stories of death, despair, and separation. Even as popular culture celebrated radio as a means of creating new electronic communities, there remained a subtext of atomization and alienation in the new technology. The article argues, in closing, that this paradox has continued to inform speculative, paranormal accounts of telecommunications across the century.
Persistence of social inequalities in modern welfare states: Explanation of a paradox
Authors: Mackenbach Johan P
Published: January 2017

Aims: Social–epidemiological explanations of health inequalities usually take the existence of social inequality as a given and ignore the fundamental questions of why social inequality exists in the first place and why it is so persistent. I review here theories of the explanation of social inequality to identify the processes and/or structures responsible for its persistence. Methods: This paper is a review of the relevant sociological literature. Results: The sociological literature suggests that what persists over long periods of time is not a specific manifestation of social inequality but a ‘meta-phenomenon’: the fact that there are different social positions, that these social positions give access to different levels of resources in some graded way and that the distribution of individuals over social positions follows rules that create inequalities in the opportunities for achieving a more advantaged social position. The durability of social inequality in this generic form can then be understood from the persistence of the underlying mechanisms and processes – for example, humans are driven by self-interest, while most objects of their striving are in short supply, therefore a struggle for rewards is present in all societies; humans are unequally endowed, therefore some are more successful in this struggle for resources than others; and the inequalities resulting from these individual level actions are structurally fixated through the intergenerational transmission of (dis)advantage, various societal institutions, and cultural factors. Conclusions: The sociological literature suggests that some mechanisms producing and perpetuating social inequality are more ‘benign’ than others. Health inequalities may be more than a consequence of social inequality and may play a more profound part by amplifying social inequalities.
Just because it’s public doesn’t mean it’s any of your business: Adults’ and children’s sexual rights in digitally mediated spaces
Authors: Albury Kath
Published: January 2017

This article engages with media responses to the 2015 Ashley Madison hack (which largely exposed the sexual details of adult heterosexual men) and the 2014 ‘Fappening’ hack (which exposed private sexual images of adult female celebrities). It draws on Petchesky’s concept of positive sexual rights and Warner’s framework of sexual ethics to reflect on the ways current educational and policy responses to ‘teen sexting’ (or sharing nude/semi-nude pictures) might change if young people’s sexual rights were recognized as being similar (if not the same) to those of the adult victims of the 2014 and 2015 hacks.
Street-level: Google Street View’s abstraction by datafication
Authors: Shapiro Aaron
Published: January 2017

While aerial photography is associated with vertical objectivity and spatial abstractions, street-level imagery appears less political in its orientation to the particularities of place. I contest this assumption, showing how the aggregation of street-level imagery into “big datasets” allows for the algorithmic sorting of places by their street-level visual qualities. This occurs through an abstraction by “datafication,” inscribing new power geometries onto urban places through algorithmic linkages between visual environmental qualities, geographic information, and valuations of social worth and risk. Though largely missing from media studies of Google Street View, similar issues have been raised in critiques of criminological theories that use place as a proxy for risk. Comparing the Broken Windows theory of criminogenesis with big data applications of street-level imagery informs a critical media studies approach to Google Street View. The final section of this article suggests alternative theoretical orientations for algorithm design that avoid the pitfalls of essentialist equations of place with social character.
Medical Management of Peripheral Arterial Disease: A Therapeutic Algorithm
Authors: Lumsden Alan B. , Rice Terry W.
Published: January 2017

Over half of the people with peripheral arterial disease (PAD) may be asymptomatic. The most common symptom of mild-to-moderate PAD is intermittent claudication, present in about one third of symptomatic patients. Patients with intermittent claudication often have severely impaired functional status. Despite the high prevalence of the disease and the strong association with cardiovascular morbidity and mortality, patients with PAD are less likely to receive appropriate treatment for their atherosclerotic risk factors than are those being treated for coronary artery disease. The goals of treatment are to prevent progression of systemic atherosclerosis and its associated morbidity and mortality, to prevent limb loss, and to improve functional capacity for symptomatic patients. For claudicating patients, medical management includes symptomatic treatment with cilostazol or pentoxifylline. For all patients, it is equally important to pursue risk reduction through exercise programs and promotion of smoking cessation, as well as with the use of statins, antiplatelet therapies, antithrombotic strategies, angiotensin-converting-enzyme inhibitors, beta-blockers, and attention to homocysteine levels. Because not all patients are symptomatic, medical management of peripheral arterial disease may proceed along an algorithmic pathway that recognizes 3 types of patients: those requiring risk reduction only, symptomatic patients with minimal lifestyle limitation, and symptomatic patients with significant lifestyle impairment.
An estrogen receptor β-selective agonist inhibits non-alcoholic steatohepatitis in preclinical models by regulating bile acid and xenobiotic receptors
Authors: Ponnusamy Suriyan , Tran Quynh T , Thiyagarajan Thirumagal , Miller Duane D , Bridges Dave , Narayanan Ramesh
Published: January 2017

Non-alcoholic steatohepatitis (NASH) affects 8–10 million people in the US and up to 75% of obese individuals. Despite this, there are no approved oral therapeutics to treat NASH and therefore the need for novel approaches exists. The estrogen receptor β (ER-β)-selective agonist, β-LGND2, inhibits body weight and white adipose tissue, and increases metabolism, resulting in higher energy expenditure and thermogenesis. Due to favorable effects of β-LGND2 on obesity, we hypothesized that β-LGND2 will prevent NASH directly by reducing lipid accumulation in the liver or indirectly by favorably changing body composition. Male C57BL/6 mice fed with high fat diet (HFD) for 10 weeks or methionine choline-deficient diet for four weeks and treated with vehicle exhibited altered liver weights by twofold and increased serum transaminases by 2–6-folds. These changes were not observed in β-LGND2-treated animals. Infiltration of inflammatory cells and collagen deposits, an indication of fibrosis, were observed in the liver of mice fed with HFD for 10 weeks, which were effectively blocked by β-LGND2. Gene expression studies in the liver indicate that pregnane X receptor target genes were significantly increased by HFD, and the increase was inhibited by β-LGND2. On the other hand, metabolomics indicate that bile acid metabolites were significantly increased by β-LGND2. These studies demonstrate that an ER-β agonist might provide therapeutic benefits in NASH by directly modulating the function of xenobiotic and bile acid receptors in the liver, which have important functions in the liver, and indirectly, as demonstrated before, by inhibiting adiposity.

Impact statement

Over 75–90% of those classified as clinically obese suffer from co-morbidities, the most common of which is non-alcoholic steatohepatitis (NASH). While there are currently no effective treatment approaches for NASH, data presented here provide preliminary evidence that an estrogen receptor β-selective ligand could have the potential to reduce lipid accumulation and inflammation, and protect liver from NASH.
Therapeutic effects of hyaluronidase on acquired lymphedema using a newly developed mouse limb model
Authors: Roh Kangsan , Cho Sungrae , Park Jae-hyun , Yoo Byong Chul , Kim Won-Ki , Kim Seok-ki , Park Kyewon , Kang Hee , Ku Jin-mo , Yeom Chang-Hwan , Lee Kyunghoon , Lee Sukchan
Published: January 2017

Acquired lymphedema is one of the most dreaded side effects of cancer treatment, such as surgical treatment or irradiation. However, due to the lack of appropriate animal models, there is no effective therapeutic method to cure acquired lymphedema. To develop a reproducible acquired lymphedema animal model, we devised a mouse hind limb model by removing a superficial inguinal lymph node, a popliteal lymph node, a deep inguinal lymph node, and the femoral lymphatic vessel. We measured the volume of lymphedematous leg and observed the change in level of hyaluronic acid (HA) and lymphangiogenic factors after injecting hyaluronidase. Our model showed the distinguishable swelling and the reliable symptoms compared to previously reported models. In the lymphedematous regions of our model, we confirmed that HA, a major component of extracellular matrix, accumulated to higher levels than in a normal mouse. This lymphedema volume was rapidly reduced by treating hyaluronidase. Following hyaluronidase injection, the lymphedematous region of our model resembled a normal hind limb. Our findings indicated that hyaluronidase promoted lymphangiogenesis on the lymphedematous limb. Based on hyaluronidase treatment in the lymphedematous region, this could potentially be a new therapeutic approach for acquired lymphedema mediated through the modification of the size of HA fragments.

Impact statement

In this manuscript, the essence of the work described in this manuscript involves the development of (1) a mouse limb model showing acquired lymphedema and (2) a potent therapeutic treatment using hyaluronidase to remedy acquired lymphedema in our model. In order to develop a reproducible acquired lymphedema animal model that reflects the most common symptoms experienced by lymphedema patients, we devised a mouse hind limb model by removing lymph nodes and lymphatics. Our model showed the distinguishable swelling and the reliable symptoms compared to previously reported models. In the lymphedematous regions of our model, we confirmed that hyaluronic acid (HA) accumulated to higher levels than in a normal mouse. This lymphedema volume was rapidly reduced by treating the lymphedematous leg with hyaluronidase, which also degraded high molecular weight HA to low molecular weight HA. Immunohistochemical analysis, quantitative real-time PCR analysis and lymphangioscintigraphy showed that hyaluronidase enhanced lymphangiogenesis in the lymphedematous limb.
Clarifying the Construct of Occupational Engagement for Occupational Therapy Practice
Authors: Kennedy Jennifer , Davis Jane A.
Published: January 2017

Occupational engagement (OE) has been presented as a core construct in occupational therapy; however, its broad conceptualization and confounding definitions are problematic. Clarifying the construct of OE would help occupational therapists to explicate the nature of their practice. The purpose of this study was to explore occupational therapists’ perspectives of the construct of OE. Qualitative descriptive methodology was used to collect data using semistructured interviews with nine practicing occupational therapists in the Greater Toronto Area. Qualitative content analysis, using an inductive approach, was employed to uncover emerging categories. Participants spoke about transitioning from therapeutic engagement to OE with a client by following a client’s path of choice. The essential elements and influencers of OE were highlighted, and the relationship between OE and occupational performance was discussed. The findings provide an initial understanding of essential elements necessary to enable clients to initiate engagement in therapy and then, subsequently, in occupations of their choice.
Frankly, We Do Give a Damn
Authors: Feldman Gilad , Lian Huiwen , Kosinski Michal , Stillwell David
Published: January 2017

There are two conflicting perspectives regarding the relationship between profanity and dishonesty. These two forms of norm-violating behavior share common causes and are often considered to be positively related. On the other hand, however, profanity is often used to express one’s genuine feelings and could therefore be negatively related to dishonesty. In three studies, we explored the relationship between profanity and honesty. We examined profanity and honesty first with profanity behavior and lying on a scale in the lab (Study 1; N = 276), then with a linguistic analysis of real-life social interactions on Facebook (Study 2; N = 73,789), and finally with profanity and integrity indexes for the aggregate level of U.S. states (Study 3; N = 50 states). We found a consistent positive relationship between profanity and honesty; profanity was associated with less lying and deception at the individual level and with higher integrity at the society level.
Efficacy of Berberine Alone and in Combination for the Treatment of Hyperlipidemia: A Systematic Review
Authors: Koppen Laura M. , Whitaker Andrea , Rosene Audrey , Beckett Robert D.
Published: January 2017

The objective of this review is to identify, summarize, and evaluate clinical trials of berberine for the treatment of hyperlipidemia and other dyslipidemias. A literature search for randomized, controlled trials of berberine that assessed at least 2 lipid values as endpoints resulted in identification of 12 articles that met criteria. The majority of evaluated articles consistently suggest that berberine has a beneficial effect on low-density lipoprotein (reductions ranging from approximately 20 to 50 mg/dL) and triglycerides (reductions ranging from approximately 25 to 55 mg/dL). Common study limitations included lack of reporting of precision in their endpoints, description of blinding, transparency in flow of patients, and reporting of baseline concomitant medications. Berberine could serve as an alternative for patients who are intolerant to statins, patients resistant to starting statin therapy but who are open to alternative treatments, and for low-risk patients not indicated for statin therapy.
Maternal Race–Ethnicity, Immigrant Status, Country of Birth, and the Odds of a Child With Autism
Authors: Fairthorne Jenny , de Klerk Nick , Leonard Helen M. , Schieve Laura A. , Yeargin-Allsopp Marshalyn
Published: January 2017

The risk of autism spectrum disorder varies by maternal race–ethnicity, immigration status, and birth region. In this retrospective cohort study, Western Australian state registries and a study population of 134 204 mothers enabled us to examine the odds of autism spectrum disorder with intellectual disability in children born from 1994 to 2005 by the aforementioned characteristics. We adjusted for maternal age, parity, socioeconomic status, and birth year. Indigenous women were 50% less likely to have a child with autism spectrum disorder with intellectual disability than Caucasian, nonimmigrant women. Overall, immigrant women were 40% less likely to have a child with autism spectrum disorder with intellectual disability than nonimmigrant women. However, Black women from East Africa had more than 3.5 times the odds of autism spectrum disorder with intellectual disability in their children than Caucasian nonimmigrant women. Research is implicated on risk and protective factors for autism spectrum disorder with intellectual disability in the children of immigrant women.
Diffuse large B-cell lymphoma genotyping on the liquid biopsy
Authors: Rossi Davide , Diop Fary , Spaccarotella Elisa , Monti Sara , Zanni Manuela , Rasi Silvia , Deambrogi Clara , Spina Valeria , Bruscaggin Alessio , Favini Chiara , Serra Roberto , Ramponi Antonio , Boldorini Renzo , Foà Robin , Gaidano Gianluca
Published: January 2017

Key Points

Plasma cfDNA genotyping is as accurate as genotyping of the diagnostic biopsy in detecting clonal somatic mutations in DLBCL. Plasma cfDNA genotyping is a real-time, noninvasive tool that can be used to track clonal evolution in DLBCL.
Initiation of acute graft-versus-host disease by angiogenesis
Authors: Riesner Katarina , Shi Yu , Jacobi Angela , Kräter Martin , Kalupa Martina , McGearey Aleixandria , Mertlitz Sarah , Cordes Steffen , Schrezenmeier Jens-Florian , Mengwasser Jörg , Westphal Sabine , Perez-Hernandez Daniel , Schmitt Clemens , Dittmar Gunnar , Guck Jochen , Penack Olaf
Published: January 2017

Key Points

Angiogenesis preceded infiltration of inflammatory leukocytes during GVHD as well as during experimental colitis. Metabolic alterations and cytoskeleton changes occurred during early angiogenesis, but classical endothelial activation signs were absent.
Exploring surface cleaning strategies in hospital to prevent contact transmission of methicillin-resistant Staphylococcus aureus
Authors: Lei Hao , Jones Rachael M. , Li Yuguo
Published: January 2017

Background

Cleaning of environmental surfaces in hospitals is important for the control of methicillin-resistant Staphylococcus aureus (MRSA) and other hospital-acquired infections transmitted by the contact route. Guidance regarding the best approaches for cleaning, however, is limited.

Methods

In this study, a mathematical model based on ordinary differential equations was constructed to study MRSA concentration dynamics on high-touch and low-touch surfaces, and on the hands and noses of two patients (in two hospitals rooms) and a health care worker in a hypothetical hospital environment. Two cleaning interventions – whole room cleaning and wipe cleaning of touched surfaces – were considered. The performance of the cleaning interventions was indicated by a reduction in MRSA on the nose of a susceptible patient, relative to no intervention.

Results

Whole room cleaning just before first patient care activities of the day was more effective than whole room cleaning at other times, but even with 100% efficiency, whole room cleaning only reduced the number of MRSA transmitted to the susceptible patient by 54%. Frequent wipe cleaning of touched surfaces was shown to be more effective that whole room cleaning because surfaces are rapidly re-contaminated with MRSA after cleaning. Wipe cleaning high-touch surfaces was more effective than wipe cleaning low-touch surfaces for the same frequency of cleaning. For low wipe cleaning frequency (≤3 times per hour), high-touch surfaces should be targeted, but for high wipe cleaning frequency (>3 times per hour), cleaning should target high- and low-touch surfaces in proportion to the surface touch frequency. This study reproduces the observations from a field study of room cleaning, which provides support for the validity of our findings.

Conclusions

Daily whole room cleaning, even with 100% cleaning efficiency, provides limited reduction in the number of MRSA transmitted to susceptible patients via the contact route; and should be supplemented with frequent targeted cleaning of high-touch surfaces, such as by a wipe or cloth containing disinfectant.
Phosphoinositol 3-phosphate acts as a timer for reactive oxygen species production in the phagosome
Authors: Song Zhi Min , Bouchab Leïla , Hudik Elodie , Le Bars Romain , Nüsse Oliver , Dupré-Crochet Sophie
Published: January 2017

Production of reactive oxygen species (ROS) in the phagosome by the NADPH oxidase is critical for mammalian immune defense against microbial infections and phosphoinositides are important regulators in this process. Phosphoinositol 3-phosphate (PI(3)P) regulates ROS production at the phagosome via p40phox by an unknown mechanism. This study tested the hypothesis that PI(3)P controls ROS production by regulating the presence of p40phox and p67phox at the phagosomal membrane. Pharmacologic inhibition of PI(3)P synthesis at the phagosome decreased the ROS production both in differentiated PLB-985 cells and human neutrophils. It also releases p67phox, the key cytosolic subunit of the oxidase, and p40phox from the phagosome. The knockdown of the PI(3)P phosphatase MTM1 or Rubicon or both increases the level of PI(3)P at the phagosome. That increase enhances ROS production inside the phagosome and triggers an extended accumulation of p67phox at the phagosome. Furthermore, the overexpression of MTM1 at the phagosomal membrane induces the disappearance of PI(3)P from the phagosome and prevents sustained ROS production. In conclusion, PI(3)P, indeed, regulates ROS production by maintaining p40phox and p67phox at the phagosomal membrane.
MFG-E8-derived peptide attenuates adhesion and migration of immune cells to endothelial cells
Authors: Hirano Yohei , Yang Weng-Lang , Aziz Monowar , Zhang Fangming , Sherry Barbara , Wang Ping
Published: January 2017

Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) plays an immunomodulatory role in inflammatory diseases. MFG-E8-derived short peptide (MSP68) greatly reduces neutrophil infiltration and injury in the lung during sepsis. In this study, we examined the effect of MSP68 on chemotaxis of various immune cells and its regulatory mechanism. Bone marrow-derived neutrophils (BMDNs) from C57BL/6 mice, human monocyte THP-1 cell line, and human T lymphocyte Jurkat cell line were used for adhesion and migration assays using a Transwell method in the presence of MSP68. Treatment with MSP68 significantly inhibited the BMDN and THP-1 cell but not Jurkat cell adhesion on the TNF-α-stimulated pulmonary artery endothelial cell (PAEC) monolayer dose-dependently. MSP68 also significantly reduced BMDN adhesion on VCAM-1-coated wells dose dependently. Surface plasmon resonance (SPR) analysis revealed that MSP68 efficiently recognized integrin α4β1 (receptor for VCAM-1) at the dissociation constant (KD) of 1.53 × 10−7 M. These findings implicate that MSP68 prevents neutrophil adhesion to the activated endothelial cells by interfering with the binding between integrin α4β1 on neutrophils and VCAM-1 on endothelial cells. Moreover, MSP68 significantly attenuated the migration of BMDN and THP-1 cells but not Jurkat cells to their chemoattractants. Pretreatment with MSP68 inhibited the transmigration of BMDNs across the PAECs toward chemoattractants, fMLP, MIP-2, and complement fragment 5a (C5a) dose-dependently. Finally, we identified that the activation of p38 MAPK in BMDNs by fMLP was inhibited by MSP68. Thus, MSP68 attenuates extravasation of immune cells through the endothelial cell lining into inflamed tissue, implicating MSP68 to be a novel, therapeutic agent for inflammatory diseases caused by excessive immune cell infiltration.
Exosomes from eosinophils autoregulate and promote eosinophil functions
Authors: Cañas José Antonio , Sastre Beatriz , Mazzeo Carla , Fernández-Nieto Mar , Rodrigo-Muñoz José Manuel , González-Guerra Andrés , Izquierdo Manuel , Barranco Pilar , Quirce Santiago , Sastre Joaquín , del Pozo Victoria
Published: January 2017

Eosinophils are able to secrete exosomes that have an undefined role in asthma pathogenesis. We hypothesized that exosomes released by eosinophils autoregulate and promote eosinophil function. Eosinophils of patients with asthma (n = 58) and healthy volunteers (n = 16) were purified from peripheral blood, and exosomes were isolated and quantified from eosinophils of the asthmatic and healthy populations. Apoptosis, adhesion, adhesion molecules expression, and migration assays were performed with eosinophils in the presence or absence of exosomes from healthy and asthmatic individuals. Reactive oxygen species (ROS) were evaluated by flow cytometry with an intracellular fluorescent probe and nitric oxide (NO) and a colorimetric kit. In addition, exosomal proteins were analyzed by mass spectrometry. Eosinophil-derived exosomes induced an increase in NO and ROS production on eosinophils. Moreover, exosomes could act as a chemotactic factor on eosinophils, and they produced an increase in cell adhesion, giving rise to a specific augmentation of adhesion molecules, such as ICAM-1 and integrin α2. Protein content between exosomes from healthy and asthmatic individuals seems to be similar in both groups. In conclusion, we found that exosomes from the eosinophils of patients with asthma could modify several specific eosinophil functions related to asthma pathogenesis and that they could contribute fundamentally to the development and maintenance of asthma.
Frontline Science: Tumor necrosis factor-α stimulation and priming of human neutrophil granule exocytosis
Authors: McLeish Kenneth R , Merchant Michael L , Creed T Michael , Tandon Shweta , Barati Michelle T , Uriarte Silvia M , Ward Richard A
Published: January 2017

Neutrophil granule exocytosis plays an important role in innate and adaptive immune responses. The present study examined TNF-α stimulation or priming of exocytosis of the 4 neutrophil granule subsets. TNF-α stimulated exocytosis of secretory vesicles and gelatinase granules and primed specific and azurophilic granule exocytosis to fMLF stimulation. Both stimulation and priming of exocytosis by TNF-α were dependent on p38 MAPK activity. Bioinformatic analysis of 1115 neutrophil proteins identified by mass spectrometry as being phosphorylated by TNF-α exposure found that actin cytoskeleton regulation was a major biologic function. A role for p38 MAPK regulation of the actin cytoskeleton was confirmed experimentally. Thirteen phosphoproteins regulated secretory vesicle quantity, formation, or release, 4 of which—Raf1, myristoylated alanine-rich protein kinase C (PKC) substrate (MARCKS), Abelson murine leukemia interactor 1 (ABI1), and myosin VI—were targets of the p38 MAPK pathway. Pharmacologic inhibition of Raf1 reduced stimulated exocytosis of gelatinase granules and priming of specific granule exocytosis. We conclude that differential regulation of exocytosis by TNF-α involves the actin cytoskeleton and is a necessary component for priming of the 2 major neutrophil antimicrobial defense mechanisms: oxygen radical generation and release of toxic granule contents.
Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA
Authors: Jiu Yaming , Peränen Johan , Schaible Niccole , Cheng Fang , Eriksson John E. , Krishnan Ramaswamy , Lappalainen Pekka
Published: January 2017

The actin and intermediate filament cytoskeletons contribute to numerous cellular processes, including morphogenesis, cytokinesis and migration. These two cytoskeletal systems associate with each other, but the underlying mechanisms of this interaction are incompletely understood. Here, we show that inactivation of vimentin leads to increased actin stress fiber assembly and contractility, and consequent elevation of myosin light chain phosphorylation and stabilization of tropomyosin-4.2 (see Geeves et al., 2015). The vimentin-knockout phenotypes can be rescued by re-expression of wild-type vimentin, but not by the non-filamentous ‘unit length form’ vimentin, demonstrating that intact vimentin intermediate filaments are required to facilitate the effects on the actin cytoskeleton. Finally, we provide evidence that the effects of vimentin on stress fibers are mediated by activation of RhoA through its guanine nucleotide exchange factor GEF-H1 (also known as ARHGEF2). Vimentin depletion induces phosphorylation of the microtubule-associated GEF-H1 on Ser886, and thereby promotes RhoA activity and actin stress fiber assembly. Taken together, these data reveal a new mechanism by which intermediate filaments regulate contractile actomyosin bundles, and may explain why elevated vimentin expression levels correlate with increased migration and invasion of cancer cells.
Role of the different eyes in the visual odometry in the wolf spider Lycosa tarantula (Araneae, Lycosidae)
Authors: Ortega-Escobar Joaquin , Ruiz Miguel A.
Published: January 2017

The wolf spider Lycosa tarantula returns home by means of path integration. Previous studies demonstrated: (i) that the angular component of the outbound run is measured using a polarized-light compass associated with the anterior median eyes; (ii) changes in direction of the substratum are detected by the anterior lateral eyes (ALEs); and (iii) in relation to the linear component of the outbound run, an increase of optic flow, in either the lateral or ventral fields of view, caused spiders to search for the burrow at a point nearer to the goal. However, the role of the secondary eyes [ALEs, posterior lateral eyes (PLEs) and posterior median eyes (PMEs)] in the perception of this optic flow and the importance of them for gauging the distance walked is still unknown. In this study, lateral or ventral gratings of wavelength λ=1 cm were used, with two groups of spiders in each setup: (1) PLEs+PMEs covered and (2) ALEs covered. The largest reduction in the distance walked to return to the burrow was observed with the ventral grating/ALEs covered. These results show the importance of the previously neglected ALEs for the visual behavior of these spiders. The possibility of gathering information for locomotion from the three pairs of secondary eyes in the mushroom bodies is discussed.
Differences in mobility at the range edge of an expanding invasive population of Xenopus laevis in the west of France
Authors: Louppe Vivien , Courant Julien , Herrel Anthony
Published: January 2017

Theoretical models predict that spatial sorting at the range edge of expanding populations should favor individuals with increased mobility relative to individuals at the center of the range. Despite the fact that empirical evidence for the evolution of locomotor performance at the range edge is rare, data on cane toads support this model. However, whether this can be generalized to other species remains largely unknown. Here, we provide data on locomotor stamina and limb morphology in individuals from two sites: one from the center and one from the periphery of an expanding population of the clawed frog Xenopus laevis in France where it was introduced about 30 years ago. Additionally, we provide data on the morphology of frogs from two additional sites to test whether the observed differences can be generalized across the range of this species in France. Given the known sexual size dimorphism in this species, we also test for differences between the sexes in locomotor performance and morphology. Our results show significant sexual dimorphism in stamina and morphology, with males having longer legs and greater stamina than females. Moreover, in accordance with the predictions from theoretical models, individuals from the range edge had a greater stamina. This difference in locomotor performance is likely to be driven by the significantly longer limb segments observed in animals in both sites sampled in different areas along the range edge. Our data have implications for conservation because spatial sorting on the range edge may lead to an accelerated increase in the spread of this invasive species in France.
Hydrodynamic detection and localization of artificial flatfish breathing currents by harbour seals (Phoca vitulina)
Authors: Niesterok Benedikt , Krüger Yvonne , Wieskotten Sven , Dehnhardt Guido , Hanke Wolf
Published: January 2017

Harbour seals are known to be opportunistic feeders, whose diet consists mainly of pelagic and benthic fish, such as flatfish. As flatfish are often cryptic and do not produce noise, we hypothesized that harbour seals are able to detect and localize flatfish using their hydrodynamic sensory system (vibrissae), as fish emit water currents through their gill openings (breathing currents). To test this hypothesis, we created an experimental platform where an artificial breathing current was emitted through one of eight different openings. Three seals were trained to search for the active opening and station there for 5 s. Half of the trials were conducted with the seal blindfolded with an eye mask. In blindfolded and non-blindfolded trials, all seals performed significantly better than chance. The seals crossed the artificial breathing current (being emitted into the water column at an angle of 45 deg to the ground) from different directions. There was no difference in performance when the seals approached from in front, from behind or from the side. All seals responded to the artificial breathing currents by directly moving their snout towards the opening from which the hydrodynamic stimulus was emitted. Thus, they were also able to extract directional information from the hydrodynamic stimulus. Hydrodynamic background noise and the swimming speed of the seals were also considered in this study as these are aggravating factors that seals in the wild have to face during foraging. By creating near-natural conditions, we show that harbour seals have the ability to detect a so-far overlooked type of stimulus.
Influence of fatiguing noise on auditory evoked responses to stimuli of various levels in a beluga whale, Delphinapterus leucas
Authors: Popov Vladimir V. , Sysueva Evgeniya V. , Nechaev Dmitry I. , Rozhnov Viatcheslav V. , Supin Alexander Ya.
Published: January 2017

The negative impact of man-made noise on the hearing of odontocetes attracts considerable recent attention. Mostly permanent or temporary reductions in sensitivity are known as permanent or temporary threshold shift (PTS or TTS, respectively) were investigated. In the present study, the effects of a fatiguing sound on the hearing of a beluga whale Delphinapterus leucas within a wide range of levels of test signals was investigated. The fatiguing noise was half-octave band-limited noise centered at 32 kHz. Post-exposure effects of this noise on the evoked responses to test stimuli (rhythmic pip trains with a 45-kHz center frequency) at various levels (from threshold to 60 dB above threshold) was measured. For baseline (pre-exposure) responses, the magnitude-vs-level function featured a segment of steep magnitude dependence on level (up to 30 dB above threshold) that was followed by a plateau segment that featured little dependence on level (30 o 55 dB above threshold). Post-exposure, the function shifted upward along the level scale. The shift was 23 dB at the threshold and up to 33 dB at supra threshold level. Due to the plateau in the magnitude-vs-level function, post-exposure suppression of responses depended on the stimulus level such that higher levels corresponded to less suppression. The experimental data may be modelled based on the compressive non-linearity of the cochlea. According to the model, post-exposure responses of the cochlea to high-level stimuli are minimally suppressed compared to the pre-exposure responses, despite a substantially increased threshold.
Activation of respiratory muscles does not occur during cold-submergence in bullfrogs,Lithobates catesbeianus
Authors: Santin Joseph M. , Hartzler Lynn K.
Published: January 2017

Semiaquatic frogs may not breathe air for several months because they overwinter in ice-covered ponds. In contrast to many vertebrates that experience decreased motor performance after inactivity, respiratory motor function in bullfrogs, Lithobates catesbeianus, remains functional following cold-submergence. Unlike mammalian hibernators with unloaded limb muscles and inactive locomotor systems, respiratory mechanics of frogs counterintuitively allow for ventilatory maneuvers when submerged. Thus we hypothesized that bullfrogs generate respiratory motor patterns during cold-submergence to avoid disuse and preserve motor performance. Accordingly, we measured activity of respiratory muscles (buccal floor compressor and glottal dilator) via electromyography in freely behaving bullfrogs at 20°C and 2°C. Although we confirm that ventilation cycles occur underwater at 20°C, bullfrogs did not activate either respiratory muscle when submerged acutely or chronically at 2°C. We conclude that cold-submerged bullfrogs endure respiratory motor inactivity, implying that other mechanisms, excluding underwater muscle activation, maintain a functional respiratory motor system throughout overwintering.
Unprecedented Property of 4,6-Di(substituted)amino-1,2-dihydro-1,3,5-triazines: Formation of Acid Salts by Simple Treatment with Alkali Metal Salts of Protic Acids
Authors: Maeda Shirou , Maeda Akihisa , Hirose Rika , Tsuri Sayaka , Takeuchi Takae , Meguro Kanji
Published: January 2017

Treatment of 4,6-di(substituted)amino-1,2-dihydro-1,3,5-triazine derivative (5) with sodium chloride in a bilayer system consisting of toluene and water gave its hydrochloride (6) in the toluene layer and sodium hydroxide in the aqueous layer. Similarly, treatment of 5, 8 and 9 with an aqueous sodium acetate solution in organic solvents resulted in the formation of their corresponding acetates, 7, 12 and 13, respectively.