bluuebunny/crossref_metadata_2025 huggingface dataset:
Stabilization of Cytokinin Levels Enhances Arabidopsis Resistance Against Verticillium longisporum
Authors: Reusche Michael , Klásková Jana , Thole Karin , Truskina Jekaterina , Novák Ondřej , Janz Dennis , Strnad Miroslav , Spíchal Lukáš , Lipka Volker , Teichmann Thomas
Published: April 2013

Verticillium longisporum is a vascular pathogen that infects the Brassicaceae host plants Arabidopsis thaliana and Brassica napus. The soilborne fungus enters the plant via the roots and colonizes the xylem of roots, stems, and leaves. During late stages of infections, Verticillium spp. spread into senescing tissue and switch from biotrophic to a necrotrophic life style. Typical symptoms of V. longisporum-induced disease are stunted growth and leaf chlorosis. Expression analyses of the senescence marker genes SENESCENCE-ASSOCIATED GENE12, SENESCENCE-ASSOCIATED GENE13, and WRKY53 revealed that the observed chlorosis is a consequence of premature senescence triggered by Verticillium infection. Our analyses show that, concomitant with the development of chlorosis, levels of trans-zeatin decrease in infected plants. Potentially, induction of cytokinin oxidase/dehydrogenase expression by Verticillium infection contributes to the observed decreases in cytokinin levels. Stabilization of Arabidopsis cytokinin levels by both pharmacological and genetic approaches inhibits Verticillium proliferation and coincides with reduced disease symptom development. In summary, our results indicate that V. longisporum triggers premature plant senescence for efficient host plant colonization.
Flexible weighing of olfactory and vector information in the desert ant
Cataglyphis fortis
Authors: Buehlmann Cornelia , Hansson Bill S. , Knaden Markus
Published: April 2013

Desert ants,
Cataglyphis fortis
, are equipped with remarkable skills that enable them to navigate efficiently. When travelling between the nest and a previously visited feeding site, they perform path integration (PI), but pinpoint the nest or feeder by following odour plumes. Homing ants respond to nest plumes only when the path integrator indicates that they are near home. This is crucial, as homing ants often pass through plumes emanating from foreign nests and do not discriminate between the plume of their own and that of a foreign nest, but should absolutely avoid entering a wrong nest. Their behaviour towards food odours differs greatly. Here, we show that in ants on the way to food, olfactory information outweighs PI information. Although PI guides ants back to a learned feeder, the ants respond to food odours independently of whether or not they are close to the learned feeding site. This ability is beneficial, as new food sources—unlike foreign nests—never pose a threat but enable ants to shorten distances travelled while foraging. While it has been shown that navigating
C. fortis
ants rely strongly on PI, we report here that the ants retained the necessary flexibility in the use of PI.
Population structure in the native range predicts the spread of introduced marine species
Authors: Gaither Michelle R. , Bowen Brian W. , Toonen Robert J.
Published: April 2013

Forecasting invasion success remains a fundamental challenge in invasion biology. The effort to identify universal characteristics that predict which species become invasive has faltered in part because of the diversity of taxa and systems considered. Here, we use an alternative approach focused on the spread stage of invasions.
F
ST
, a measure of alternative fixation of alleles, is a common proxy for realized dispersal among natural populations, summarizing the combined influences of life history, behaviour, habitat requirements, population size, history and ecology. We test the hypothesis that population structure in the native range (
F
ST
) is negatively correlated with the geographical extent of spread of marine species in an introduced range. An analysis of the available data (29 species, nine phyla) revealed a significant negative correlation (
R
2
= 0.245–0.464) between
F
ST
and the extent of spread of non-native species. Mode
F
ST
among pairwise comparisons between populations in the native range demonstrated the highest predictive power (
R
2
= 0.464,
p
< 0.001). There was significant improvement when marker type was considered, with mtDNA datasets providing the strongest relationship (
n
= 21,
R
2
= 0.333–0.516). This study shows that
F
ST
can be used to make qualitative predictions concerning the geographical extent to which a non-native marine species will spread once established in a new area.
Young APOE4 targeted replacement mice exhibit poor spatial learning and memory, with reduced dendritic spine density in the medial entorhinal cortex
Authors: Rodriguez Gustavo A. , Burns Mark P. , Weeber Edwin J. , Rebeck G. William
Published: April 2013

The apolipoprotein E4 (APOE-ε4) allele is the strongest genetic risk factor for developing late-onset Alzheimer’s disease, and may predispose individuals to Alzheimer’s-related cognitive decline by affecting normal brain function early in life. To investigate the impact of human APOE alleles on cognitive performance in mice, we trained 3-mo-old APOE targeted replacement mice (E2, E3, and E4) in the Barnes maze to locate and enter a target hole along the perimeter of the maze. Long-term spatial memory was probed 24 h and 72 h after training. We found that young E4 mice exhibited significantly impaired spatial learning and memory in the Barnes maze compared to E3 mice. Deficits in spatial cognition were also present in a second independent cohort of E4 mice tested at 18 mo of age. In contrast, cognitive performance in the hidden platform water maze was not as strongly affected by APOE genotype. We also examined the dendritic morphology of neurons in the medial entorhinal cortex of 3-mo-old TR mice, neurons important to spatial learning functions. We found significantly shorter dendrites and lower spine densities in basal shaft dendrites of E4 mice compared to E3 mice, consistent with spatial learning and memory deficits in E4 animals. These findings suggest that human APOE-ε4 may affect cognitive function and neuronal morphology early in life.
Elastic moduli and the aspect ratio spectrum of rock using simulated annealing
Authors: Izumotani Satoshi , Onozuka Shigenobu
Published: April 2013

We propose a new method for estimating pore volume concentrations associated with inclusions with different aspect ratios and also the rock matrix and pore fluid moduli using very fast simulated annealing. We use the Kuster and Toksöz effective modulus formulations as a forward model that takes the pore shapes into consideration.

In order to provide this method, we first estimated the model parameters, then calculated the P‐ and S‐wave velocities as a function of pressure in dry and saturated conditions and finally compared the calculated velocities with the measured ultrasonic velocities of sandstone, limestone and granite. The calculated velocity fitted well with the measured velocity. Furthermore, we verified the calculated bulk modulus and shear modulus of the rock matrix. As these moduli were consistent with the results from other experiments and were almost the same as those by the inversion method, we believe that this method can satisfactorily calculate the moduli.

Next, we conducted optimization under several cases of moduli setting. We obtained the best results using the independent shear modulus under saturated conditions. The result indicates that the shear modulus varies according to the fluid in the pores in sandstone.

Finally, we optimized the average aspect ratio of rock and found that the average aspect ratio may depend on the type of rock. The velocity calculated by the single aspect ratio is similar to the velocity calculated by using a spectrum of aspect ratios for the same rock.
Representation, agendas and institutions
Authors: Bevan Shaun , Jennings Will
Published: April 2013

Dynamic agenda representation can be understood through the transmission of the priorities of the public onto the policy priorities of government. The pattern of representation in policy agendas is mediated through institutions due to friction (i.e., organisational and cognitive costs imposed on change) in decision making and variation in the scarcity of policy makers' attention. This article builds on extant studies of the correspondence between public priorities and the policy activities of government, undertaking time‐series analyses using data for the United States and the United Kingdom, from 1951 to 2003, relating to executive speeches, laws and budgets in combination with data on public opinion about the ‘most important problem’. The results show that the responsiveness of policy agendas to public priorities is greater when institutions are subject to less friction (i.e., executive speeches subject to few formal rules and involving a limited number of actors) and declines as friction against policy change increases (i.e., laws and budgets subject to a greater number of veto points and political interests/coalitions).
In vitro differentiation of near‐unlimited numbers of functional mouse basophils using conditional Hoxb8
Authors: Gurzeler U. , Rabachini T. , Dahinden C. A. , Salmanidis M. , Brumatti G. , Ekert P. G. , Echeverry N. , Bachmann D. , Simon H. U. , Kaufmann T.
Published: April 2013

Background

Basophils constitute a rare leukocyte population known for their effector functions in inflammation and allergy, as well as more recently described immunoregulatory roles. Besides their low frequency, functional analysis of basophils is hindered by a short life span, inefficient ex vivo differentiation protocols, and lack of suitable cell models. A method to produce large quantities of basophils in vitro would facilitate basophil research and constitute a sought‐after tool for diagnostic and drug testing purposes.

Methods

A method is described to massively expand bone marrow–derived basophils in vitro. Myeloid progenitors are conditionally immortalized using Hoxb8 in the presence of interleukin‐3 (IL‐3) and outgrowing cell lines selected for their potential to differentiate into basophils upon shutdown of Hoxb8 expression.

Results

IL‐3‐dependent, conditional Hoxb8‐immortalized progenitor cell lines can be expanded and maintained in culture for prolonged periods. Upon shutdown of Hoxb8 expression, near‐unlimited numbers of mature functional basophils can be differentiated in vitro within six days. The cells are end‐differentiated and short‐lived and express basophil‐specific surface markers and proteases. Upon IgE‐ as well as C5a‐mediated activation, differentiated basophils release granule enzymes and histamine and secrete Th2‐type cytokines (IL‐4, IL‐13) and leukotriene C4. IL‐3‐deprivation induces apoptosis correlating with upregulation of the BH3‐only proteins BCL‐2‐interacting mediator of cell death (BIM) and p53 upregulated modulator of apoptosis (PUMA) and downregulation of proviral integration site for Moloney murine leukemia virus 1 kinase (PIM‐1).

Conclusion

A novel method is presented to generate quantitative amounts of mouse basophils in vitro, which moreover allows genetic manipulation of conditionally immortalized progenitors. This approach may represent a useful alternative method to isolating primary basophils.
Moments of Meeting: The Relational Challenges of Sexuality in the Consulting Room
Authors: Renn Paul
Published: April 2013

In this paper, I explore the relational challenges of sexuality in the consulting room, as informed by developmental studies and ‘moments’ theory, and discuss the contentious issue of self‐disclosure. I acknowledge that there has been a hiatus in recent decades in the discussion of psychosexuality in psychoanalysis, linked to a shift from Freud's drive theory to post‐Freudian developmental theories, as well as to the change in the role of the therapist that this has entailed. While I also acknowledge that these changes have resulted in a certain de‐eroticization and de‐sexualization of psychoanalysis, I point to research showing that sexuality is, in fact, very much alive in the consulting room, but also to a gap in training on such issues, and to a concomitant lacuna in the literature discussing sexual attraction between therapist and patient. Before discussing the ethical and relational challenges of sexuality in the consulting room, I summarize the evolution of sexuality in psychoanalytic thinking and briefly discuss relevant developmental perspectives. I question the view that a developmental model is not suited to effectively working with sexual material. I illustrate theoretical points with a clinical case study, a development of previously published work (Renn, 2012).
The Mother, The Psychoanalyst, The Poet and The Artist: Containment and Growth of The Mind
Authors: Tolliday Heather
Published: April 2013

This paper considers the difficulties which humans have in using and developing their capacity for thought. Growth of the human mind, through attunement of the mother's unconscious experience with the infant's, is explored along with the distortions which arise because of aversion to uncertainty and suffering. It then looks at psychoanalysis and the verbal and visual arts in the light of the maternal function, and the way in which they also promote the growth of the mind. Four products of the human mind – an excerpt from an infant observation published in 1998, some post‐Kleinian psychoanalytic clinical case material from the 1980s, John Keats's 19th century Ode to a Nightingale and Lucas Cranach's 1526 painting, Adam and Eve – are used to illustrate some of the similarities and differences among them in giving conscious form to the unconscious.
YL529, a novel, orally available multikinase inhibitor, potently inhibits angiogenesis and tumour growth in preclinical models
Authors: Xu Youzhi , Lin Hongjun , Meng Nana , Lu Wenjie , Li Guobo , Han Yuanyuan , Dai Xiaoyun , Xia Yong , Song Xiangrong , Yang Shengyong , Wei Yuquan , Yu Luoting , Zhao Yinglan
Published: April 2013

Background and Purpose

Targeted chemotherapy using small‐molecule inhibitors of angiogenesis and proliferation is a promising strategy for cancer therapy.

Experimental Approach

YL529 was developed via computer‐aided drug design, de novo synthesis and high‐throughput screening. The biochemical, pharmacodynamic and toxicological profiles of YL529 were investigated using kinase and cell viability assays, a mouse tumour cell‐containing alginate bead model, a zebrafish angiogenesis model and several human tumour xenograft models in athymic mice.

Key Results

In vitro, YL529 selectively inhibited the activities of VEGFR2/VEGFR3 and serine/threonine kinase RAF kinase. YL529 inhibited VEGF165‐induced phosphorylation of VEGFR2, as well as the proliferation, migration, invasion and tube formation of human umbilical vascular endothelial cells. It also significantly blocked vascular formation and angiogenesis in the zebrafish model. Moreover, YL529 strongly attenuated the proliferation of A549 cells by disrupting the RAF/mitogen‐activated protein (MAP) or extracellular signal‐regulated kinase (Erk) kinase (MEK) kinase kinase/MAPK pathway. Oral administration of YL529 (37.5–150 mg−1·kg−1·day−1) to nude mice bearing established tumour xenografts significantly prevented the growth (60–80%) of A549, SPC‐A1, A375, OS‐RC‐2 and HCT116 tumours without detectable toxicity. YL529 markedly reduced microvessel density and increased tumour cell apoptosis in the tumours formed in mice inoculated with the lung cancer cells, SPC‐A1 and A549, and the colon carcinoma cells, HCT116.

Conclusions and Implications

YL529, an orally active multikinase inhibitor, shows therapeutic potential for solid tumours, and warrants further investigation as a possible anticancer agent.
Delayed onset of graft-versus-host disease in immunodeficent human leucocyte antigen-DQ8 transgenic, murine major histocompatibility complex class II-deficient mice repopulated by human peripheral blood mononuclear cells
Authors: Büchner S M , Sliva K , Bonig H , Völker I , Waibler Z , Kirberg J , Schnierle B S
Published: April 2013

Haematopoietic humanization of mice is used frequently to study the human immune system and its reaction upon experimental intervention. Immunocompromised non-obese diabetic (NOD)-Rag1–/– mice, additionally deficient for the common gamma chain of cytokine receptors (γc) (NOD-Rag1–/– γc–/– mice), lack B, T and natural killer (NK) cells and allow for efficient human peripheral mononuclear cell (PBMC) engraftment. However, a major experimental drawback for studies using these mice is the rapid onset of graft-versus-host disease (GVHD). In order to elucidate the contribution of the xenogenic murine major histocompatibility complex (MHC) class II in this context, we generated immunodeficient mice expressing human MHC class II [human leucocyte antigen (HLA)-DQ8] on a mouse class II-deficient background (Aβ–/–). We studied repopulation and onset of GVHD in these mouse strains following transplantation of DQ8 haplotype-matched human PBMCs. The presence of HLA class II promoted the repopulation rates significantly in these mice. Virtually all the engrafted cells were CD3+ T cells. The presence of HLA class II did not advance B cell engraftment, such that humoral immune responses were undetectable. However, the overall survival of DQ8-expressing mice was prolonged significantly compared to mice expressing mouse MHC class II molecules, and correlated with an increased time span until onset of GVHD. Our data thus demonstrate that this new mouse strain is useful to study GVHD, and the prolonged animal survival and engraftment rates make it superior for experimental intervention following PBMC engraftment.
Vertical osteoconductivity and early bone formation of titanium–zirconium and titanium implants in a subperiosteal rabbit animal model
Authors: Kämmerer Peer W. , Palarie Victor , Schiegnitz Eik , Hagmann Sebastien , Alshihri Abdulmonem , Al‐Nawas Bilal
Published: April 2013

Objectives

The aim of this pilot study was to evaluate the vertical osteoconductive and osteointegrative dynamics around titanium–zirconium (TiZr) implants compared to titanium (Ti) implants.

Materials and methods

In a split‐leg design, 12 TiZr‐SLActive and 12 Ti‐SLActive implants were inserted 3 mm above bone level in the proximal tibia of 12 rabbits. Full periosteal flaps were repositioned to cover the site. Specimens were obtained after 10, 20 and 30 days (each n = 4 per group). Histomorphometric measurements included percentage of linear bone fill (PLF; %), new marginal vertical bone height (VBH; mm) and vertical bone‐to‐implant contact (vBIC; %). Statistical analysis was performed with the nonparametric F1_LD_F1 model to compare the two groups at the different time points.

Results

After 10 days, mean PLF was 7.7% (standard deviation (SD): 5.3) for TiZr and 17.6 (SD: 8.3) for Ti. Mean VBH was 0.35 mm (SD: 0.15) and 0.78 mm (SD: 0.4) for TiZr and Ti, respectively; mean vBIC was 24.4% (SD: 41) for TiZr and 53% (SD: 28.9) for Ti samples. The differences were significant for all parameters (PLF: P = 0.021; VBH: P = 0.009; vBIC: P = 0.011). After 20 days, mean PLF was 44.3% (SD: 26.3) for TIZr and 46.2% (SD: 21.3) for Ti implants. TiZr showed a mean VBH of 1.73 mm (SD: 1) and 1.8 mm (SD: 0.6) for Ti samples. Mean vBIC had values of 48.3% (SD: 23.7) and 68.7% (SD: 35.5) for TiZr and Ti, respectively (PLF: P = 0.78; VBH: P = 0.58; vBIC: P = 0.47). At the point of 30 days, mean PLF values were 23.7% (SD: 3.8) for TiZr and 28.9% (SD: 21.7) for Ti samples; mean for VBH in TiZr samples was 0.65 mm (SD: 0.39) and 1.7 mm (SD: 1.1) for Ti ones. Finally, mean vBIC was 28.3% (SD: 19.3) and 54.4% (SD: 26.5) for TiZr and Ti samples, respectively (PLF: P = 0.1; VBH: P = 0.088; vBIC: P = 0.089).

Conclusions

A significant delay in vertical osteoconductivity at the earliest time point under examination was seen for TiZr implants when compared to their Ti counterparts. For the later points, TiZr as well as Ti implants demonstrated comparable values in this animal model. The long‐term osteogenic surface properties of equally pretreated TiZr dental implants are therefore similar to those of Ti implants in vivo.
Identifying early markers for future school achievement in children with early‐onset epilepsy
Authors: Ronen Gabriel M
Published: April 2013

This commentary is on the original article by Berg et al. on pages 661–667 of this issue.
Cardiovascular safety of sulfonylureas: a meta‐analysis of randomized clinical trials
Authors: Monami M. , Genovese S. , Mannucci E.
Published: April 2013

Aim

Cardiovascular safety of sulfonylurea has been questioned by some authors. This article aims at collecting all available data on this issue from randomized trials.

Methods

A meta‐analysis was performed including all trials with a duration of at least 6 months, comparing a sulfonylurea with a non‐sulfonylurea agent in type 2 diabetes. Major cardiovascular events (MACE) and mortality were retrieved and combined to calculate Mantel‐Haenzel odds ratio (MH‐OR).

Results

Of the 115 selected trials, 62 reported information on MACE, and 30 reported at least one event. MH‐OR for sulfonylurea was 1.08 [0.86–1.36], p = 0.52 (1.85 [1.20–2.87], p = 0.005, in the five trials vs. DPP4 inhibitors, no significant differences vs. other comparators). The MH‐OR for myocardial infarction and stroke was 0.88 [0.75–1.04], p = 0.13 and 1.28 [1.03–1.60], p = 0.026, respectively. Mortality was significantly increased with sulfonylureas (MH‐OR: 1.22 [1.01–1.49], p = 0.047).

Conclusions

In type 2 diabetes, the use of sulfonylureas is associated with increased mortality and a higher risk of stroke, whereas the overall incidence of MACE appears to be unaffected. Significant differences in cardiovascular risk could be present in direct comparisons with specific classes of glucose‐lowering agents, such as DPP4 inhibitors, but this hypothesis needs to be confirmed in long‐term cardiovascular outcomes trials. The results of this meta‐analysis need to be interpreted with caution, mainly because of limitations in trial quality and under‐reporting of information on cardiovascular events and mortality. However, the cardiovascular safety of sulfonylureas cannot be considered established unless it is evaluated in long‐term cardiovascular outcomes trials.
Complete reorganization of the motor cortex of adult rats following long‐term spinal cord injuries
Authors: Tandon Shashank , Kambi Niranjan , Mohammed Hisham , Jain Neeraj
Published: April 2013

Understanding brain reorganization following long‐term spinal cord injuries is important for optimizing recoveries based on residual function as well as developing brain‐controlled assistive devices. Although it has been shown that the motor cortex undergoes partial reorganization within a few weeks after peripheral and spinal cord injuries, it is not known if the motor cortex of rats is capable of large‐scale reorganization after longer recovery periods. Here we determined the organization of the rat (Rattus norvegicus) motor cortex at 5 or more months after chronic lesions of the spinal cord at cervical levels using intracortical microstimulation. The results show that, in the rats with the lesions, stimulation of neurons in the de‐efferented forelimb motor cortex no longer evokes movements of the forelimb. Instead, movements of the body parts in the adjacent representations, namely the whiskers and neck were evoked. In addition, at many sites, movements of the ipsilateral forelimb were observed at threshold currents. The extent of representations of the eye, jaw and tongue movements was unaltered by the lesion. Thus, large‐scale reorganization of the motor cortex leads to complete filling‐in of the de‐efferented cortex by neighboring representations following long‐term partial spinal cord injuries at cervical levels in adult rats.
Social Capital and Entrepreneurship: A Schema and Research Agenda
Authors: Gedajlovic Eric , Honig Benson , Moore Curt B. , Payne G. Tyge , Wright Mike
Published: April 2013

This introduction to the special issue considers past and current research on “Social Capital and Entrepreneurship” to develop a schema and an associated research agenda. With the general goal of establishing social capital as a foundational theory of entrepreneurship, we discuss how future research can utilize social capital perspectives across levels of analysis and contexts to explain a wide variety of entrepreneurship phenomena.
A novel two‐stage model for cloud service trustworthiness evaluation
Authors: Fan Wenjuan , Yang Shanlin , Pei Jun
Published: April 2013

In this paper, we address the cloud service trustworthiness evaluation problem, which in essence is a multi‐attribute decision‐making problem, by proposing a novel evaluation model based on the fuzzy gap measurement and the evidential reasoning approach. There are many sources of uncertainties in the process of cloud service trustworthiness evaluation. In addition to the intrinsic uncertainties, cloud service providers face the problem of discrepant evaluation information given by different users from different perspectives. To address these problems, we develop a novel fuzzy gap evaluation approach to assess cloud service trustworthiness and to provide evaluation values from different perspectives. From the evaluation values, the perception–importance, delivery–importance, and perception–delivery gaps are generated. These three gaps reflect the discrepancy evaluation of cloud service trustworthiness in terms of perception utility, delivery utility, and importance utility, respectively. Finally, the gap measurement of each perspective is represented by a belief structure and aggregated using the evidential reasoning approach to generate final evaluation results for informative and robust decision making. From this hybrid two‐stage evaluation process, cloud service providers can get improvement suggestions from intermediate information derived from the gap measurement, which is the main advantage of this evaluation process.
Why are Stock Splits Declining?
Authors: Minnick Kristina , Raman Kartik
Published: April 2013

The percentage of firms undertaking stock splits has fallen from a peak of 23% in 1982 to less than 1% in 2009. Controlling for time trends and other economic determinants, the declining incidence of stock splits is significantly associated with a drop in household investors’ equity holdings and with a rise in household income. We also report a decline in the size of split factors that is associated with an increase in institutional ownership of equity and with an increase in household income. Collectively, the evidence is consistent with firms responding rationally to changes in investor characteristics.
TAX COMPETITION IN A SIMPLE MODEL WITH HETEROGENEOUS FIRMS: HOW LARGER MARKETS REDUCE PROFIT TAXES*
Authors: Haufler Andreas , Stähler Frank
Published: April 2013

We set up a simple two‐country model of tax competition where firms with different productivity decide in which location to produce and sell output. In this model, a unique, asymmetric Nash equilibrium is shown to exist, provided that countries are sufficiently different with respect to their exogenous market size. Sorting of firms occurs in equilibrium, as the smaller country levies the lower tax rate and attracts the low‐cost firms. A simultaneous expansion of both markets that raises the profitability of firms intensifies tax competition and causes both countries to reduce their tax rates, despite higher corporate tax bases.
I’LL NEVER FORGET MY FIRST CIGARETTE: A REVEALED PREFERENCE ANALYSIS OF THE “HABITS AS DURABLES” MODEL*
Authors: Demuynck Thomas , Verriest Ewout
Published: April 2013

We provide a revealed preference analysis of the “habits as durables” model. This approach avoids the need to impose a functional form on the underlying utility function. We show that our characterization is testable by means of linear programming methods, and we demonstrate its practical usefulness by means of an application to cigarette consumption using a Spanish household consumption data set. We find that the “habits as durables” model has better empirical fit in terms of predictive success compared to the “short memory habits” and life cycle models.
Discovery of a novel HLA‐DRB1*04:05 variant, DRB1*04:05:15, in a Taiwanese and the probable HLA haplotype in association with DRB1*04:05:15
Authors: Yang K. L. , Lee S. K. , Lin P. Y.
Published: April 2013

Here, we report a novel HLA‐DRB1*04 allele, DRB1*04:05:15, found in a Taiwanese unrelated volunteer bone marrow hematopoietic stem cell donor by a sequence‐based typing (SBT) method. The DNA sequence of DRB1*04:05:15 is identical to the sequence of DRB1*04:05:01 in exon 2, except the nucleotide at the position 198 where C is substituted by T (TAC→TAT at codon 37). Due to the silent mutation, the nucleotide replacement generated no amino acid variation in comparison with DRB1*04:05:01. We postulate the allele DRB1*04:05:15 was probably derived from DRB1*04:05:01 via a nucleotide point mutation event. The probable HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 haplotype in association with DRB1*04:05:15 may be deduced as A*02:01‐B*48:01‐C*08:03‐DRB1*04:05:15‐DQB1*04:01.
Immunophenotyping of selected hematologic disorders – focus on lymphoproliferative disorders with more than one malignant cell population
Authors: Porwit A.
Published: April 2013

Currently, clinical laboratories face increasing demand for flow cytometry testing combined with limited funding. Therefore, many laboratories search for panels that would provide sufficient immunophenotyping information and meet economical requirements. At the Flow Cytometry Laboratory, University Health Network, Toronto, ON, Canada, we apply two 10‐color tubes of surface markers for diagnosis of lymphoproliferative disorders (LPDs). These tubes contain most of the mandatory B‐ and T‐cell markers according to European Leukemia Net (www.leukemia-net.org) recommendations. The B‐cell‐oriented panel includes the following antibodies: Kappa‐FITC/lambda‐PE/CD19‐ECD/CD38‐PC5.5/CD20‐PC7/CD34‐APC/CD23 APC‐AF700/CD10 APC‐AF750/CD5‐PB/CD45‐KO. A different combination is applied to detect cytoplasmic Ig light chain expression and aberrant immunophenotype of plasma cells. The T‐cell panel allows enumeration of various T‐ and NK‐cell subsets: CD57‐FITC/CD11c‐PE/CD8‐ECD/CD3‐PC5.5/CD2‐PC7/CD56‐APC/CD7‐APC‐AF700/CD4‐APC‐AF750/CD5‐PB/CD45‐KO. The reported overall incidence of B‐cell chronic LPDs presenting with more than one aberrant population is approximately 5%. Multicolor analysis facilitates the detection of multiple aberrant populations in the same sample because expression of multiple antigens can be studied simultaneously in each defined population. Examples of LPDs with multiple aberrant populations are presented.
Acute myeloid leukemia: advances in diagnosis and classification
Authors: Hasserjian R. P.
Published: April 2013

Acute myeloid leukemia is an aggressive myeloid neoplasm characterized by ≥20% myeloblasts in the blood or bone marrow. Current treatment strategies for acute myeloid leukemia are based on both patient‐related parameters such as age and performance status as well as the intrinsic characteristics of particular disease subtypes. Subtyping of acute myeloid leukemia requires an integration of information from the patient's clinical history (such as any prior preleukemic myeloid neoplasm or cytotoxic potentially leukemogenic therapy), the leukemia morphology, cytogenetic findings, and the mutation status of particular genes (NPM1, FLT3, and CEBPA). In recent years, a barrage of information has become available regarding gene mutations that occur in acute myeloid leukemia and their influence on prognosis. Future therapies for acute myeloid leukemia will increasingly rely on the genetic signatures of individual leukemias and will adjust therapy to the predicted disease aggressiveness as well as employ therapies targeted against particular deregulated genetic pathways. This article reviews current standards for diagnosing and classifying acute myeloid leukemia according to the 2008 WHO Classification. Data that have subsequently accumulated regarding newly characterized gene mutations are also presented. It is anticipated that future leukemia classifications will employ a combination of karyotypic features and the gene mutation pattern to stratify patients to increasingly tailored treatment plans.
Factor VII assay performance: an analysis of the North American Specialized Coagulation Laboratory Association proficiency testing results
Authors: Zantek N. D. , Hsu P. , Refaai M. A. , Ledford‐Kraemer M. , Meijer P. , Van Cott E. M.
Published: April 2013

The performance of factor VII (FVII) assays currently used by clinical laboratories was examined in North American Specialized Coagulation Laboratory Association (NASCOLA) proficiency tests. Data from 12 surveys conducted between 2008 and 2010, involving 20 unique specimens plus four repeat‐tested specimens, were analyzed. The number of laboratories per survey was 49–54 with a total of 1224 responses. Numerous reagent/instrument combinations were used. For FVII > 80 or <40 U/dL, 99.5% of results (859/863) were correctly classified by laboratories as normal/abnormal. Classification of specimens with 40–73 U/dL FVII was heterogeneous. Interlaboratory precision was better for normal specimens (coefficient of variation (CV) 10.7%) than for FVII<20 U/dL (CV 33.1%), with a mean CV of 17.2% per specimen. Intralaboratory precision for repeated specimens demonstrated no significant difference between the paired survey results (mean absolute difference 2.5–5.0 U/dL). For specimens with FVII >50 U/dL, among commonly used methods, one thromboplastin and one calibrator produced results 5–6 U/dL higher and another thromboplastin and calibrator produced results 5–6 U/dL lower than all other methods, and human thromboplastin differed from rabbit by +7.6 U/dL. Preliminary evidence suggests these differences could be due to the calibrator. For FVII <50 U/dL, differences among the commonly used reagents and calibrators were generally not significant.
Platelets: bridging hemostasis, inflammation, and immunity
Authors: Jenne C. N. , Urrutia R. , Kubes P.
Published: April 2013

Although the function of platelets in the maintenance of hemostasis has been studied in great detail, more recent evidence has highlighted a central role for platelets in the host inflammatory and immune responses. Platelets by virtue of their large numbers and their ability to rapidly release a broad spectrum of immunomodulatory cytokines, chemokines, and other mediators act as circulating sentinels. Upon detection of a pathogen, platelets quickly activate and begin to drive the ensuing inflammatory response. Platelets have the ability to directly modulate the activity of neutrophils (phagocytosis, oxidative burst), endothelium (adhesion molecule and chemokine expression), and lymphocytes. Due to their diverse array of adhesion molecules and preformed chemokines, platelets are able to adhere to leukocytes and facilitate their recruitment to sites of tissue damage or infection. Furthermore, platelets directly participate in the capture and sequestration of pathogens within the vasculature. Platelet–neutrophil interactions are known to induce the release of neutrophil extracellular traps (NETs) in response to either bacterial or viral infection, and platelets have been shown to internalize pathogens, sequestering them in engulfment vacuoles. Finally, emerging data indicate that platelets also participate in the host immune response by directly killing infected cells. This review will highlight the central role platelets play in the initiation and modulation of the host inflammatory and immune responses.
An investigation of prescription and over-the-counter supply of ophthalmic chloramphenicol in Wales in the 5 years following reclassification
Authors: Du Hank C T , John Dai N , Walker Roger
Published: April 2013

Objectives

The aims of the study were to (i) quantify the sales of over-the-counter (OTC) ophthalmic chloramphenicol from all community pharmacies in Wales and investigate the impact on primary care prescriptions up to 5 years after reclassification and (ii) investigate the temporal relationship between items supplied OTC and on NHS primary care prescriptions.

Methods

Primary care prescription data (2004–2010) and OTC sales data (2005–2010) for ophthalmic chloramphenicol were obtained. The quantity sold OTC was calculated from pharmacy wholesale records and sales data from a large pharmacy multiple. Spearman’s rank correlation for prescription and OTC supplies of ophthalmic chloramphenicol was calculated for data from January 2008 to December 2010.

Key findings

OTC supply of chloramphenicol eye drops and ointment were both highest in 2007–2008 and represented 68% (57 708/84 304) and 48% (22 875/47 192) of the corresponding prescription volume, respectively. There was a steady year-on-year increase in the combined supply of OTC ophthalmic chloramphenicol and that dispensed on prescription from 144 367 items in 2004–2005 to 210 589 in 2007–2008 before stabilising in 2008–2009 and 2009–2010. A significant positive correlation was observed between prescription items and OTC sales of chloramphenicol eye drops and ointment combined (r = 0.7, P < 0.001).

Conclusion

OTC availability increased the total quantity of ophthalmic chloramphenicol supplied in primary care compared to that seen prior to reclassification. Although growth in the sales of ophthalmic chloramphenicol OTC has stabilised and the supply pattern mirrors primary care prescribers, further work is required to investigate whether use is appropriate and whether the publication of updated practice guidance has changed this.
The Dynamics of Age and Sex in the Development of Mother–Infant Vocal Communication Between 3 and 11 Months
Authors: Sung Jihyun , Fausto‐Sterling Anne , Garcia Coll Cynthia , Seifer Ronald
Published: April 2013

We followed the nondistressed vocalization dynamics of 30 mother–infant dyads observed in a naturalistic setting using multiple time points between 3 and 11 months to identify subtle relationships between age, sex and maternal behavior ending by 1 year of age with diverging trajectories of nondistressed vocalization. We observed no mean differences between boys and girls in frequency or duration of nondistressed vocalizations at any one time period. However, while these parameters were essentially static for boys, girls showed a quadratic developmental curve, declining in frequency and duration between 6 and 8 months and climbing above their early starting point by 9–11 months. Mothers of boys showed a linear decrease in the duration of their speech over the 9 months of our study. In contrast, mothers of girls showed quadratic patterns of ultimately increasing vocalization frequency and duration, over the months 3–11 of development. Finally, boys' and girls' vocalization contingent to maternal speech revealed no differences. Mothers of boys, however, did not change significantly over time, while mothers of girls showed an increase in contingent responsiveness from 3–5 months to 9–11 months and from 6–8 months to 9–11 months. A similar pattern was followed for object‐related maternal vocal responses.
A rare case of gingival myiasis in a 2‐year‐old child
Authors: Arslan Selçuk , İslamoğlu Ayla , Çobanoğlu Bengü
Published: April 2013

Background

Myiasis is the infestation of live human and vertebrate animal with larvae of Diptera fly which feed on the host dead or living tissue. Gingival myiasis is a very rare disease and associated with poor oral hygiene, senility, suppurative oral lesions, mental retardation and other conditions.

Case Report

A case of gingival myiasis in a 2‐year‐old otherwise healthy child is reported. Treatment consisted of mechanical removal of larvae, extraction of the adjacent devitalized teeth and debridment of necrotic tissues.

Conclusion

Clinicians dealing with oral medicine should be aware of this very rare condition in children.
How to assess the prediction accuracy of species presence–absence models without absence data?
Authors: Li Wenkai , Guo Qinghua
Published: April 2013

It is very common that only presence data are available in ecological niche modeling. However, most existing methods for evaluating the accuracy of presence–absence (binary) predictions of species require presence–absence data. The aim of this study is to present a new method for accuracy assessment that does not rely on absence data.

Two new statistics Fpb and Fcpb were derived based on presence–background data. With generated six virtual species, we used DOMAIN, generalized linear modeling (GLM), and maximum entropy (MAXENT) to produce different species presence–absence predictions. To investigate the effectiveness of the new statistics in accuracy assessment, we used Fpb, Fcpb, the traditional F‐measure (F), kappa coefficient, true skill statistic (TSS), area under the receiver operating characteristic curve (AUC), and the contrast validation index (CVI) to evaluate the accuracy of predictions, and the behaviors of these accuracy measures were compared. The effectiveness of Fpb for threshold selection and estimation of species prevalence was also investigated.

Experimental results show that Fcpb is an estimate of F. The Pearson's correlation coefficient (COR) between Fcpb and F is 0.9882, with a root‐mean‐square error (RMSE) of 0.0171. In general, Fpb, Fcpb, F, kappa coefficient, TSS, and CVI can sort models by the accuracy of binary prediction, but AUC is not appropriate to evaluate the accuracy of binary prediction. For DOMAIN, GLM, and MAXENT, finding the threshold by maximizing Fpb and by maximizing F result in similar accuracies. In addition, the estimation of species prevalence based on binary output with maximizing Fpb as the thresholding method is significantly more accurate than simply averaging the original continuous output. The best estimate of prevalence is provided by the binary output of MAXENT, with an RMSE of 0.0116.

Finally, we conclude that the new method is promising in accuracy assessment, threshold selection, and estimation of species prevalence, all of which are important but challenging problems with presence‐only data. Because it does not require absence data, the new method will have important applications in ecological niche modeling.
Abusive supervision and subordinate emotional labor: The moderating role of openness personality
Authors: Wu Tsung‐Yu , Hu Changya
Published: April 2013

We investigated the differential relationships between abusive supervision and two emotional labor strategies used by subordinates (surface acting and deep acting). Furthermore, we examined whether subordinates' openness personality moderated the above relationships. Using the questionnaire survey method, we collected data from 210 employees in China. The results of hierarchical regression showed that abusive supervision related positively to surface acting (regulating facial expression) but negatively to deep acting (regulating inner feeling). Openness personality moderated the relationships between abusive supervision and the two emotional labor strategies, such that the relationships were stronger for employees with lower openness. Findings of our study contribute to the literature on workplace emotions and negative leadership.
The combined effects of land‐use legacies and novel fire regimes on bird distributions in the Mediterranean
Authors: De Cáceres Miquel , Brotons Lluís , Aquilué Núria , Fortin Marie‐Josée
Published: April 2013

Aim

We investigate first whether fire regimes resulting from the combination of climate change and fire‐fighting policy may affect species distributions in Mediterranean landscapes, and second to what extent distributional dynamics may be constrained by the spatial legacy of historical land use.

Location

Catalonia (north‐eastern Spain).

Methods

We modelled the distributional responses of 64 forest and open‐habitat bird species to nine fire‐regime scenarios, defined by combining different levels of climate change and fire suppression efficiency. A fire‐succession model was used to stochastically simulate land‐cover changes between 2000 and 2050 under these scenarios. We used species distribution models to predict habitat suitability and occupancy dynamics under either no dispersal or full dispersal assumptions.

Results

Under many simulated scenarios, the succession from shrubland to forest dominated over the creation of new low‐vegetation areas derived from wildfires. Consequently, open‐habitat specialists were the group most affected by losses of suitable habitat. Fire regimes obtained under scenarios including high fire suppression efficiency resulted in a larger number of bird species experiencing reductions in their distribution area.

Main conclusions

Anthropogenic factors, such as historical land‐use change and fire suppression, can drive regional distribution dynamics in directions opposite to those expected from climatic trends. This raises the question of what drivers and interactions should be given priority in the prediction of biodiversity responses to global change at the regional scale.
Clinical profile of generalized vitiligo patients with associated autoimmune/autoinflammatory diseases
Authors: van Geel N. , Speeckaert M. , Brochez L. , Lambert J. , Speeckaert R.
Published: April 2013

Background

The significance of associated autoimmune/autoinflammatory diseases in generalized vitiligo patients with respect to their clinical profile has not yet been completely established.

Objective

The objective of this study was to evaluate the clinical significance of associated autoimmune/autoinflammatory diseases in generalized vitiligo patients with respect to some general clinical variables, distribution pattern, disease activity and treatment response.

Methods

Seven hundred generalized vitiligo patients were included in this retrospective observational cohort study.

Results

Associated autoimmune/autoinflammatory diseases were present in 15.4% of the patient population and were more common in women compared with men, especially concerning thyroid disease. Only vitiligo patients with thyroid disease had clear different clinical characteristics. The percentage of total body surface area involvement was significantly (P = 0.005) higher in the presence of thyroid disease which was more pronounced in women compared with men. Patients with thyroid disease had a particular predisposition to acral and joint depigmentations. No clear differences in disease activity or response to therapy were observed in vitiligo patients with or without autoimmune/autoinflammatory disorders.

Conclusion

The presence of associated autoimmune/autoinflammatory diseases seems to influence the clinical profile of generalized vitiligo patients. Our results support the hypothesis that in the presence of a thyroid disorder, the disease activity of vitiligo is more extensive, in particular on areas prone to friction.