bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flight Initiation Distance and Starting Distance: Biological Effect or Mathematical Artefact?
Authors: Dumont François , Pasquaretta Cristian , Réale Denis , Bogliani Giuseppe , von Hardenberg Achaz 
Published: August 2012

AbstractIn many studies, flight initiation distance (FID, the distance at which a prey starts to flee at the approach of a walker) is positively related to starting distance (SD, the distance at which the walker begins to approach) and alert distance (AD, the distance at which the focal individual becomes alert to the threat). In spite of the fundamental differences between SD, a covariate that may not have any biological effect, and AD, a measure related to the behaviour of the animal, it is common to use SD as a proxy for AD when AD is hard to measure (e.g. in species that do not exhibit distinguishable alert postures). However, the relationship between SD and AD or FID may not have any biological reasons, but may instead simply result from a mathematical artefact because of the constraints SD ≥ AD ≥ FID. Under such constrains, the homoscedasticity assumption is violated, and thus, the classical null hypothesis of linear regression (slope = 0) is invalid. In this study, we first show that using SD as a proxy for AD can strongly affect the results on FID. Using data from FID tests on alpine marmots (Marmota marmota), a linear mixed model with AD as a covariate, suggested that the interaction between previous activity and AD had an effect on FID, while this effect was not detected when SD replaced AD as the covariate in the analysis. We then propose that the actual statistical test of the relationship between SD, AD and FID should be based on a null hypothesis that incorporates the constraint SD ≥ AD ≥ FID ≥ 0 and generate 95% CI of simulated slopes obtained from random values under this constraint. This null hypothesis can be rejected if the observed slope of the relationship between two of these variables is outside the 95% CI. We demonstrated that, for alpine marmots, the observed slope of the relationship between AD and SD was within the 95% CI of the simulated slopes. The absence of a statistically significant biological effect in the relationship between SD and AD raises important questions on the outcome of relationship between SD and FID. In Alpine marmot flight, decision should be studied separating the effect of SD on AD and the effect of AD on FID.
Expressions and inhibitory functions of CD300a receptors on purified human basophils
Authors: Gibbs Bernhard F. , Sabato Vito , Bridts Chris H. , Ebo Didier G. , Ben‐Zimra Micha , Levi‐Schaffer Francesca 
Published: August 2012

AbstractThe inhibitory myeloid immunoglobulin receptor CD300a (IRp60) has been shown to downregulate mast cell and eosinophil activities, thereby serving as a potential target for inhibiting allergic effector cell input in allergy. Our aims were to study the expression and functional properties of this receptor in purified human basophils, cells that crucially contribute to Th2‐type immunity and allergy. Basophils homogeneously expressed CD300a as well as the inhibitory receptor CD200R on their cell surface, and these expressions increased after anti‐IgE stimulation. IgE‐mediated basophil degranulation was also significantly inhibited by crosslinking of either CD200R or CD300a (by 90% and 50%, respectively). Inhibitory SHIP‐1 phosphorylations were also induced by CD200R and CD300a, although they were not noticeably increased by IgE‐dependent activation. We conclude that both CD200R and CD300a play a role in reducing IgE‐mediated basophil function and may crucially govern the known differential activities of these cells in vivo.
In vitro formation of organized structure between keratinocytes and dorsal‐root‐ganglion cells
Authors: Tsutsumi Moe , Nakatani Masashi , Kumamoto Junichi , Denda Sumiko , Denda Mitsuhiro 
Published: August 2012

AbstractWe recently found that the morphology in a co‐culture system of keratinocytes and dorsal‐root ganglion‐derived cells depended on the timing of seeding of the two cell types. In skin, epidermis is formed first, followed by construction of peripheral nerve structure. Therefore, we hypothesized that formation of peripheral nerve structure in the epidermis might be driven by interaction between keratinocytes and nerve cells. In the present study, we tested this idea by incubating keratinocytes and dorsal‐root ganglion cells in a spatially separated manner and observing the morphological changes in the co‐culture system. Extension of nerve fibre‐like structures from the ganglion cells was observed, and within 3 days after seeding, many nerve fibre‐like extensions penetrated into the keratinocyte cluster, subsequently forming a network that appeared to resemble the cutaneous peripheral nervous system. Our present model may be useful for studying the formation of peripheral nerve structure in the skin.
Long‐term evolutionary and ecological responses of calcifying phytoplankton to changes in atmospheric CO2
Authors: Hannisdal Bjarte , Henderiks Jorijntje , Liow Lee Hsiang 
Published: August 2012

AbstractCalcifying phytoplankton play an important role in marine ecosystems and global biogeochemical cycles, affecting the transfer of both organic and inorganic carbon from the surface to the deep ocean. Coccolithophores are the most prominent members of this group, being well adapted to low‐nutrients environments (e.g., subtropical gyres). Despite urgent concerns, their response to rising atmospheric carbon dioxide levels (pCO2) and ocean acidification is still poorly understood, and short‐term experiments may not extrapolate into longer‐term climatic adaptation. Current atmospheric pCO2 (~390 ppmv) is unprecedented since at least 3 million years ago (Ma), and levels projected for the next century were last seen more than 34 Ma. Hence, a deep‐time perspective is needed to understand the long‐term effects of high pCO2 on the biosphere. Here we combine a comprehensive fossil data set on coccolithophore cell size with a novel measure of ecological prominence: Summed Common Species Occurrence Rate (SCOR). The SCOR is decoupled from species richness, and captures changes in the extent to which coccolithophores were common and widespread, based on global occurrences in deep‐sea sediments. The size and SCOR records are compared to state‐of‐the‐art data on climatic and environmental changes from 50 to 5 Ma. We advance beyond simple correlations and trends to quantify the relative strength and directionality of information transfer among these records. Coccolithophores were globally more common and widespread, larger, and more heavily calcified in the pre‐34 Ma greenhouse world, and declined along with pCO2 during the Oligocene (34–23 Ma). Our results suggest that atmospheric pCO2 has exerted an important long‐term control on coccolithophores, directly through its availability for photosynthesis or indirectly via weathering supply of resources for growth and calcification.
Human phagosome processing of Mycobacterium tuberculosis antigens is modulated by interferon‐γ and interleukin‐10
Authors: Bobadilla Karen , Sada Eduardo , Jaime Maria E. , González Yolanda , Ramachandra Lakshmi , Rojas Roxana E. , Pedraza‐Sánchez Sigifredo , Michalak Colette , González‐Noriega Alfonso , Torres Martha 
Published: August 2012

SummaryIntracellular pathogens, such as Mycobacterium tuberculosis, reside in the phagosomes of macrophages where antigenic processing is initiated. Mycobacterial antigen–MHC class II complexes are formed within the phagosome and are then trafficked to the cell surface. Interferon‐γ (IFN‐γ) and interleukin‐10 (IL‐10) influence the outcome of M. tuberculosis infection; however, the role of these cytokines with regard to the formation of M. tuberculosis peptide–MHC‐II complexes remains unknown. We analysed the kinetics and subcellular localization of M. tuberculosis peptide–MHC‐II complexes in M. tuberculosis‐infected human monocyte‐derived macrophages (MDMs) using autologous M. tuberculosis‐specific CD4+ T cells. The MDMs were pre‐treated with either IFN‐γ or IL‐10 and infected with M. tuberculosis. Cells were mechanically homogenized, separated on Percoll density gradients and manually fractionated. The fractions were incubated with autologous M. tuberculosis ‐specific CD4+ T cells. Our results demonstrated that in MDMs pre‐treated with IFN‐γ, M. tuberculosis peptide–MHC‐II complexes were detected early mainly in the phagosomal fractions, whereas in the absence of IFN‐γ, the complexes were detected in the endosomal fractions. In MDMs pre‐treated with IL‐10, the M. tuberculosis peptide–MHC‐II complexes were retained in the endosomal fractions, and these complexes were not detected in the plasma membrane fractions. The results of immunofluorescence microscopy demonstrated the presence of Ag85B associated with HLA‐DR at the cell surface only in the IFN‐γ‐treated MDMs, suggesting that IFN‐γ may accelerate M. tuberculosis antigen processing and presentation at the cell membrane, whereas IL‐10 favours the trafficking of Ag85B to vesicles that do not contain LAMP‐1. Therefore, IFN‐γ and IL‐10 play a role in the formation and trafficking of M. tuberculosis peptide–MHC‐II complexes.
A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
Authors: Mendell Jeanne , Noveck Robert J. , Shi Minggao 
Published: August 2012

AimsTo evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of edoxaban, an oral direct factor Xa inhibitor, in healthy subjects switching from warfarin.MethodsSeventy‐two subjects were randomized to edoxaban 60 mg once daily (n = 48) or matching placebo (n = 24) for 5 days at 24 h after the last dose of warfarin treatment (INR 2.0 to 3.0). Safety/tolerability was the primary outcome measure. Pharmacokinetics, INR, aPTT, anti‐FXa, thrombin generation and other coagulation assays were assessed.ResultsSeventy‐two subjects were randomized and 64 subjects received at least one dose of edoxaban (n = 43) or placebo (n = 21) after achieving a target INR of 2.0 to 3.0 on warfarin treatment. Edoxaban 60 mg administered 24 h post‐warfarin appeared to be safe and well tolerated. Adverse events were similar across treatments. For bleeding‐related adverse events, eight subjects tested positive for faecal occult blood, five subjects during warfarin treatment and three subjects during edoxaban treatment. The mean (SD) baseline (post‐dose of warfarin) INR was 2.31 (0.193) which increased to 3.84 (0.744) over 2 h during the edoxaban treatment (P < 0.0001 vs. placebo), returning to post‐warfarin baseline within 12 h. A similar time course of effects for the other coagulation assays was observed in accordance with the drugs' mechanisms of action.ConclusionIn this study of healthy subjects, edoxaban administered 24 h after the last dose of warfarin was safe and well tolerated with transient increases across the various coagulation assays above post‐warfarin baseline levels.
Higher anticholinergic drug scale (ADS) scores are associated with peripheral but not cognitive markers of cholinergic blockade. Cross sectional data from 21 Norwegian nursing homes
Authors: Kersten Hege , Molden Espen , Willumsen Tiril , Engedal Knut , Wyller Torgeir Bruun 
Published: August 2012

AimThis study evaluated a presumed gradual decline in cognitive function in nursing home residents when the anticholinergic drug scale (ADS) score increased above 3.MethodThe study population was recruited from 21 nursing homes in Norway. Criteria for inclusion were ADS score ≥ 3 and no severe dementia, defined as Clinical Dementia Rating (CDR) score < 3. Primary cognitive end points were CERAD 10‐word lists for recall and Mini Mental State Examination (MMSE). Secondary end points were activity of daily living (ADL), mouth dryness and serum anticholinergic activity (SAA). The patients were stratified into subgroups according to ADS score, i.e. a reference group with score 3 and test groups with scores 4, 5 or ≥6. End points were compared by analyses of covariance (ancova).ResultsOverall, 230 of the 1101 screened nursing home residents (21%) had an ADS score ≥3. After exclusion 101 residents were recruited and among these, 87 managed to participate in the study. No significant differences were detected in cognitive function or ADL when ADS increased above 3 (P > 0.10), but in vivo (mouth dryness) and in vitro (SAA) measures of peripheral anticholinergic activity were significantly higher in patients with an ADS score ≥6 (P < 0.01).ConclusionThe present study does not support a progressive decline in cognitive function with ADS score above 3. This might indicate that the ADS score model has limited potential to predict the clinical risk of central anticholinergic side effects in frail elderly patients receiving multiple anticholinergic drugs.
Comparison of cell proliferation and epigenetic modification of gene expression patterns in canine foetal fibroblasts and adipose tissue‐derived mesenchymal stem cells
Authors: Oh H. J. , Park E. J. , Lee S. Y. , Soh J. W. , Kong I. S. , Choi S. W. , Ra J. C. , Kang S. K. , Lee B. C. 
Published: August 2012

AbstractObjectivesThis study compared rate of cell proliferation, viability, cell size, expression patterns of genes related to pluripotency and epigenetic modification between canine foetal fibroblasts (cFF) and canine adipose tissue‐derived mesenchymal stem cells (cAd‐MSC).Materials and methodsProliferation pattern, cell viability as well as cell size at each passage of cFF and cAd‐MSC were measured when cultures reached confluence. In addition, real‐time PCR was performed to investigate expression of Dnmt1, HDAC1, OCT4, SOX2, BAX, BCL2 genes with reference to β‐actin gene expression as an endogenous control in both cell lines.ResultscFF and cAd‐MSC differed in number of generations, but not in doubling times, at all passages. Mean cell size of cAd‐MSC was significantly smaller than that of cFF. Cell viability was significantly lower in cFFs and apoptotic level was significantly lower in cAd‐MSC compared to passage‐matched cFF. In the expression of genes related to pluripotency and epigenetic modification, level of HDAC1 in cAd‐MSC was significantly higher than in cFF, but expression of Dnmt1 did not differ between the two groups. OCT4 and SOX2 were significantly more highly expressed in cAd‐MSC compared to cFF.ConclusionscAd‐MSC have higher stem‐cell potential than cFF in terms of proliferation patterns, epigenetic modification and pluripotency, thus cAd‐MSC could be more appropriate than cFF as donors of nuclei in somatic cell nuclear transfer for transgenesis.
Efficacy and immunomodulatory actions of ONO-4641, a novel selective agonist for sphingosine 1-phosphate receptors 1 and 5, in preclinical models of multiple sclerosis
Authors: Komiya T , Sato K , Shioya H , Inagaki Y , Hagiya H , Kozaki R , Imai M , Takada Y , Maeda T , Kurata H , Kurono M , Suzuki R , Otsuki K , Habashita H , Nakade S 
Published: August 2012

Summary
ONO-4641 is a next-generation sphingosine 1-phosphate (S1P) receptor agonist selective for S1P receptors 1 and 5. The objective of the study was to characterize the immunomodulatory effects of ONO-4641 using preclinical data. ONO-4641 was tested in both in-vitro pharmacological studies as well as in-vivo models of transient or relapsing–remitting experimental autoimmune encephalomyelitis (EAE). In vitro, ONO-4641 showed highly potent agonistic activities versus S1P receptors 1 and 5 [half maximal effective concentration (EC50) values of 0·0273 and 0·334 nM, respectively], and had profound S1P receptor 1 down-regulating effects on the cell membrane. ONO-4641 decreased peripheral blood lymphocyte counts in rats by inhibiting lymphocyte egress from secondary lymphoid tissues. In a rat experimental autoimmune encephalomyelitis (EAE) model, ONO-4641 suppressed the onset of disease and inhibited lymphocyte infiltration into the spinal cord in a dose-dependent manner at doses of 0·03 and 0·1 mg/kg. Furthermore, ONO-4641 prevented relapse of disease in a non-obese diabetic mouse model of relapsing-remitting EAE. These observations suggest that ONO-4641 may provide therapeutic benefits in the treatment of multiple sclerosis.
To be or not to be faithful: flexible fidelity to foraging trails in the leaf‐cutting antAcromyrmex lobicornis
Authors: ELIZALDE LUCIANA , FARJI‐BRENER ALEJANDRO 
Published: August 2012

1. Ants using trails to forage have to select between two alternative routes at bifurcations, using two, potentially conflicting, sources of information to make their decision: individual experience to return to a previous successful foraging site (i.e. fidelity) and ant traffic. In the field, we investigated which of these two types of information individuals of the leaf‐cutting antAcromyrmex lobicornisEmery use to decide which foraging route to take.2. We measured the proportion of foraging ants returning to each trail of bifurcations the following day, and for 4–7 consecutive days. We then experimentally increased ant traffic on one trail of the bifurcation by adding additional food sources to examine the effect of increased ant traffic on the decision that ants make.3. Binomial tests showed that for 62% of the trails, ant fidelity was relatively more important than ant traffic in deciding which bifurcation to follow, suggesting the importance of previous experience.4. When information conflict was generated by experimentally increasing ant traffic along the trail with less foraging activity, most ants relied on ant traffic to decide. However, in 33% of these bifurcations, ants were still faithful to their trail. Thus, there is some degree of flexibility in the decisions thatA. lobicornismake to access food resources.5. This flexible fidelity results in individual variation in the response of workers to different levels of ant traffic, and allows the colony to simultaneously exploit both established and recently discovered food patches, aiding efficient food gathering.
Asymmetric priority effects influence the success of invasive forest insects
Authors: MILLER‐PIERCE MAILEA R. , PREISSER EVAN L. 
Published: August 2012

1. Settlement timing is often an important factor in interspecific herbivore interactions, as early‐arriving species may encounter higher resource availability and/or avoid induced defences. Despite the general importance of priority effects to the outcome of herbivore interactions, there has been little exploration of such interactions on woody host plants where their impact can only be measured over multiple years.2. In the eastern U.S.A., two invasive species, the hemlock woolly adelgid Adelges tsugae and the elongate hemlock scale Fiorinia externa, share a native host, eastern hemlock Tsuga canadensis. Their interaction and its consequences were investigated for plant growth – hemlock saplings that had been inoculated with either A. tsugae or F. externa, starting in spring 2007, were cross‐infested with the other insect in spring 2009. A set of uninfested trees was simultaneously infested with A. tsugae, F. externa, both, or neither insect (= control), and insect density and plant growth was assessed in all treatments.3. Adelges tsugae settlement rates did not differ if it settled alone or simultaneously with F. externa, but were ∼45% lower on trees previously infested with F. externa. There was no difference in F. externa settlement rates, and plant growth did not differ substantively between any of the herbivore treatments.4. At a temporal scale (i.e. multiple growing seasons) appropriate to interactions between woody plants and their herbivores, this work demonstrates that plant‐mediated priority effects can substantially affect herbivore settlement and thus the outcome of interspecific competition.
Acute lung injury results from failure of neutrophil de‐priming: a new hypothesis
Authors: Singh Nanak R. P. , Johnson Andrew , Peters A. Michael , Babar Judith , Chilvers Edwin R. , Summers Charlotte 
Published: August 2012

Eur J Clin Invest 2012; 42 (12): 1342–1349AbstractNeutrophils are the most abundant circulating white cell in humans and play a crucial role in the innate immune response. Accumulation and activation of neutrophils, together with delayed clearance, have been shown to be a key event in the pathogenesis of acute lung injury. Previously, it has been proposed that there is substantial pooling of neutrophils within the pulmonary vasculature, even under physiological conditions, making the lung especially vulnerable to neutrophil‐mediated tissue injury. However, more recent evidence suggests that only primed neutrophils accumulate in the pulmonary vasculature. This article examines the evidence for these two opposing views and proposes a new two‐step model for the recruitment of neutrophils into the lung. Firstly, neutrophils that become primed, by exposure to a range of inflammatory mediators or physicochemical perturbations, become shape changed and stiff because of alterations in their cytoskeleton, and as a result, accumulate within the pulmonary circulation. In the absence of further stimuli, the healthy pulmonary vasculature is able to selectively retained these primed cells, allow them to ‘de‐prime’ and be released back into the circulation in a quiescent, state. If this pulmonary ‘de‐priming’ mechanism fails, or a second insult occurs, such as ventilator‐associated barotrauma, which causes loss of alveolar integrity, primed neutrophils migrate from the pulmonary vasculature into the interstitial space with resultant lung injury. This canonical ‘two step’ model highlights the importance of neutrophil priming in the genesis of lung injury and the importance of adopting strategies to minimise alveolar injury.
Comprehensive care of the patient with haemophilia and inhibitors undergoing surgery: practical aspects
Authors: Kulkarni R. 
Published: August 2012

SummaryCongenital haemophilia is a rare and complex condition for which dedicated specialized and comprehensive care has produced measurable improvements in clinical outcomes and advances in patient management. Among these advances is the ability to safely perform surgery in patients with inhibitor antibodies to factors VIII and IX, in whom all but the most necessary of surgeries were once avoided due to the risk for uncontrollable bleeding due to ineffectiveness of replacement therapy. Nevertheless, surgery continues to pose a major challenge in this relatively rare group of patients because of significantly higher costs than in patients without inhibitors, as well as a high risk for bleeding and other complications. Because of the concentration of expertise and experience, it is recommended that any surgery in patients with haemophilia and inhibitors be planned in conjunction with a haemophilia treatment centre (HTC) and performed in a hospital that incorporates a HTC. Coordinated, standard pre‐, intra‐ and postoperative assessments and planning are intended to optimize surgical outcome and utilization of resources, including costly factor concentrates and other haemostatic agents, while minimizing the risk for bleeding and other adverse consequences both during and after surgery. This article will review the special considerations for patients with inhibitors as they prepare for and move through surgery and recovery, with an emphasis on the roles and responsibilities of individual members of the multidisciplinary team in facilitating this process.