bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between Auditory Pitch and Visual Elevation Do Not Depend on Language: Evidence from a Remote Population
Authors: Parkinson Carolyn , Kohler Peter Jes , Sievers Beau , Wheatley Thalia
Published: September 2012

Associations between auditory pitch and visual elevation are widespread in many languages, and behavioral associations have been extensively documented between height and pitch among speakers of those languages. However, it remains unclear whether perceptual correspondences between auditory pitch and visual elevation inform these linguistic associations, or merely reflect them. We probed this cross-modal mapping in members of a remote Kreung hill tribe in northeastern Cambodia who do not use spatial language to describe pitch. Participants viewed shapes rising or falling in space while hearing sounds either rising or falling in pitch, and reported on the auditory change. Associations between pitch and vertical position in the Kreung were similar to those demonstrated in populations where pitch is described in terms of spatial height. These results suggest that associations between visual elevation and auditory pitch can arise independently of language. Thus, widespread linguistic associations between pitch and elevation may reflect universally predisposed perceptual correspondences.
EB1 acetylation by P300/CBP-associated factor (PCAF) ensures accurate kinetochore–microtubule interactions in mitosis
Authors: Xia Peng , Wang Zhikai , Liu Xing , Wu Bing , Wang Juncheng , Ward Tarsha , Zhang Liangyu , Ding Xia , Gibbons Gary , Shi Yunyu , Yao Xuebiao
Published: September 2012

In eukaryotes, microtubules are essential for cellular plasticity and dynamics. Here we show that P300/CBP-associated factor (PCAF), a kinetochore-associated acetyltransferase, acts as a negative modulator of microtubule stability through acetylation of EB1, a protein that controls the plus ends of microtubules. PCAF acetylates EB1 on K220 and disrupts the stability of a hydrophobic cavity on the dimerized EB1 C terminus, which was previously reported to interact with plus-end tracking proteins (TIPs) containing the SxIP motif. As determined with an EB1 acetyl-K220–specific antibody, K220 acetylation is dramatically increased in mitosis and localized to the spindle microtubule plus ends. Surprisingly, persistent acetylation of EB1 delays metaphase alignment, resulting in impaired checkpoint silencing. Consequently, suppression of Mad2 overrides mitotic arrest induced by persistent EB1 acetylation. Thus, our findings identify dynamic acetylation of EB1 as a molecular mechanism to orchestrate accurate kinetochore–microtubule interactions in mitosis. These results establish a previously uncharacterized regulatory mechanism governing localization of microtubule plus-end tracking proteins and thereby the plasticity and dynamics of cells.
cAMP response element modulator α controls
IL2
and
IL17A
expression during CD4 lineage commitment and subset distribution in lupus
Authors: Hedrich Christian M. , Crispin Jose C. , Rauen Thomas , Ioannidis Christina , Apostolidis Sokratis A. , Lo Mindy S. , Kyttaris Vasileios C. , Tsokos George C.
Published: September 2012

Appropriate expression of IL-2 plays a central role during the priming and differentiation of T cells. A tight balance between IL-2 and the effector cytokine IL-17A is essential for immune homeostasis. Epigenetic mechanisms have been documented as a key component of cytokine regulation during lineage commitment. The molecular mechanisms that induce chromatin remodeling are less well understood. We investigated epigenetic regulators that mediate the diametric expression of IL-2 and IL-17A in naive, central memory, and effector memory CD4
+
T cells. We demonstrate that cAMP response modulator (CREM)α contributes to epigenetic remodeling of
IL2
in effector memory T cells through the recruitment of DNMT3a. CREMα also reduces CpG-DNA methylation of the
IL17A
promoter. CREMα expression is regulated at the epigenetic level by CpG-DNA methylation, which allows increased CREMα expression in effector memory CD4
+
T cells. T cells from patients with systemic lupus erythematosus (SLE) express increased levels of CREMα and exhibit a phenotype that is similar to effector memory CD4
+
T cells with epigenetically predetermined expression patterns of IL-2 and IL-17A. We conclude that CREMα mediates epigenetic remodeling of the
IL2
and
IL17A
gene during T-cell differentiation in favor of effector memory T cells in health and disease.
integIRTy: a method to identify genes altered in cancer by accounting for multiple mechanisms of regulation using item response theory
Authors: Tong Pan , Coombes Kevin R.
Published: September 2012

Motivation: Identifying genes altered in cancer plays a crucial role in both understanding the mechanism of carcinogenesis and developing novel therapeutics. It is known that there are various mechanisms of regulation that can lead to gene dysfunction, including copy number change, methylation, abnormal expression, mutation and so on. Nowadays, all these types of alterations can be simultaneously interrogated by different types of assays. Although many methods have been proposed to identify altered genes from a single assay, there is no method that can deal with multiple assays accounting for different alteration types systematically.

Results: In this article, we propose a novel method, integration using item response theory (integIRTy), to identify altered genes by using item response theory that allows integrated analysis of multiple high-throughput assays. When applied to a single assay, the proposed method is more robust and reliable than conventional methods such as Student’s t-test or the Wilcoxon rank-sum test. When used to integrate multiple assays, integIRTy can identify novel-altered genes that cannot be found by looking at individual assay separately. We applied integIRTy to three public cancer datasets (ovarian carcinoma, breast cancer, glioblastoma) for cross-assay type integration which all show encouraging results.

Availability and implementation: The R package integIRTy is available at the web site http://bioinformatics.mdanderson.org/main/OOMPA:Overview.

Contact:  kcoombes@mdanderson.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
A new shrinkage estimator for dispersion improves differential expression detection in RNA-seq data
Authors: Wu Hao , Wang Chi , Wu Zhijin
Published: September 2012

Recent developments in RNA-sequencing (RNA-seq) technology have led to a rapid increase in gene expression data in the form of counts. RNA-seq can be used for a variety of applications, however, identifying differential expression (DE) remains a key task in functional genomics. There have been a number of statistical methods for DE detection for RNA-seq data. One common feature of several leading methods is the use of the negative binomial (Gamma–Poisson mixture) model. That is, the unobserved gene expression is modeled by a gamma random variable and, given the expression, the sequencing read counts are modeled as Poisson. The distinct feature in various methods is how the variance, or dispersion, in the Gamma distribution is modeled and estimated. We evaluate several large public RNA-seq datasets and find that the estimated dispersion in existing methods does not adequately capture the heterogeneity of biological variance among samples. We present a new empirical Bayes shrinkage estimate of the dispersion parameters and demonstrate improved DE detection.
From Pioneers to Team Players: TGA Transcription Factors Provide a Molecular Link Between Different Stress Pathways
Authors: Gatz Christiane
Published: September 2012

The plant immune system encompasses an arsenal of defense genes that is activated upon recognition of a pathogen. Appropriate adjustment of gene expression is mediated by multiple interconnected signal transduction cascades that finally control the activity of transcription factors. These sequence-specific DNA-binding proteins act at the interface between the DNA and the regulatory protein network. In 1989, tobacco TGA1a was cloned as the first plant transcription factor. Since then, multiple studies have shown that members of the TGA family play important roles in defense responses against biotrophic and necrotrophic pathogens and against chemical stress. Here, we review 22 years of research on TGA factors which have yielded both consistent and conflicting results.
The Benyvirus RNA Silencing Suppressor Is Essential for Long-Distance Movement, Requires Both Zinc-Finger and NoLS Basic Residues but Not a Nucleolar Localization for Its Silencing-Suppression Activity
Authors: Chiba Sotaro , Hleibieh Kamal , Delbianco Alice , Klein Elodie , Ratti Claudio , Ziegler-Graff Véronique , Bouzoubaa Salah , Gilmer David
Published: September 2012

The RNA silencing-suppression properties of Beet necrotic yellow vein virus (BNYVV) and Beet soil-borne mosaic virus (BSBMV) cysteine-rich p14 proteins have been investigated. Suppression of RNA silencing activities were made evident using viral infection of silenced Nicotiana benthamiana 16C, N. benthamiana agroinfiltrated with green fluorescent protein (GFP), and GF-FG hairpin triggers supplemented with viral suppressor of RNA silencing (VSR) constructs or using complementation of a silencing-suppressor-defective BNYVV virus in Chenopodium quinoa. Northern blot analyses of small-interfering RNAs (siRNAs) in agroinfiltration tests revealed reduced amounts of siRNA, especially secondary siRNA, suggesting that benyvirus VSR act downstream of the siRNA production. Using confocal laser-scanning microscopy imaging of infected protoplasts expressing functional p14 protein fused to an enhanced GFP reporter, we showed that benyvirus p14 accumulated in the nucleolus and the cytoplasm independently of other viral factors. Site-directed mutagenesis showed the importance of the nucleolar localization signal embedded in a C4 zinc-finger domain in the VSR function and intrinsic stability of the p14 protein. Conversely, RNA silencing suppression appeared independent of the nucleolar localization of the protein, and a correlation between BNYVV VSR expression and long-distance movement was established.
Jack-of-all-trades: phenotypic plasticity facilitates the invasion of an alien slug species
Authors: Knop Eva , Reusser Nik
Published: September 2012

Invasive alien species might benefit from phenotypic plasticity by being able to (i) maintain fitness in stressful environments (‘robust’), (ii) increase fitness in favourable environments (‘opportunistic’), or (iii) combine both abilities (‘robust and opportunistic’). Here, we applied this framework, for the first time, to an animal, the invasive slug,
Arion lusitanicus
, and tested (i) whether it has a more adaptive phenotypic plasticity compared with a congeneric native slug,
Arion fuscus
, and (ii) whether it is robust, opportunistic or both. During one year, we exposed specimens of both species to a range of temperatures along an altitudinal gradient (700–2400 m a.s.l.) and to high and low food levels, and we compared the responsiveness of two fitness traits: survival and egg production
.
During summer, the invasive species had a more adaptive phenotypic plasticity, and at high temperatures and low food levels, it survived better and produced more eggs than
A. fuscus
, representing the robust phenotype. During winter,
A. lusitanicus
displayed a less adaptive phenotype than
A. fuscus
. We show that the framework developed for plants is also very useful for a better mechanistic understanding of animal invasions. Warmer summers and milder winters might lead to an expansion of this invasive species to higher altitudes and enhance its spread in the lowlands, supporting the concern that global climate change will increase biological invasions.
Association of IRGM Polymorphisms and Susceptibility to Pulmonary Tuberculosis in Zahedan, Southeast Iran
Authors: Bahari Gholamreza , Hashemi Mohammad , Taheri Mohsen , Naderi Mohammad , Eskandari-Nasab Ebrahim , Atabaki Mahdi
Published: September 2012

Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. IRGM1 is an important protein in the innate immune response against intracellular pathogens by regulating autophagy. Polymorphisms in the IRGM genes are known to influence expression levels and may be associated with outcome of infections. This case-control study was done on 150 patients with PTB and 150 healthy subjects to determine whether the IRGM polymorphisms at positions −1208 A/G (rs4958842), −1161 C/T (rs4958843), and −947 C/T (rs4958846) were associated with PTB. The polymorphisms were determined using tetra-amplification refractory mutation system-PCR (T-ARMS-PCR). The results showed that the IRGM −1161 C/T and −947 C/T polymorphisms were associated with decreased susceptibility to PTB (OR = 0.06, 95% CI = 0.03–0.13,P < 0.001 and OR = 0.27; 95% CI = 0.013–0.55,P < 0.001, resp.). No significant difference was found among the groups regarding −1208 A/G polymorphism. In conclusion we found that the IRGM −1161 C/T and −947 C/T polymorphisms but not −1208 A/G polymorphism provide relative protection against PTB in a sample of Iranian population.
Understanding Cellular Mechanisms Underlying Airway Epithelial Repair: Selecting the Most Appropriate Animal Models
Authors: Yahaya B.
Published: September 2012

Understanding the mechanisms underlying the process of regeneration and repair of airway epithelial structures demands close characterization of the associated cellular and molecular events. The choice of an animal model system to study these processes and the role of lung stem cells is debatable since ideally the chosen animal model should offer a valid comparison with the human lung. Species differences may include the complex three-dimensional lung structures, cellular composition of the lung airway as well as transcriptional control of the molecular events in response to airway epithelium regeneration, and repair following injury. In this paper, we discuss issues related to the study of the lung repair and regeneration including the role of putative stem cells in small- and large-animal models. At the end of this paper, the author discuss the potential for using sheep as a model which can help bridge the gap between small-animal model systems and humans.
Ncoa3 functions as an essential Esrrb coactivator to sustain embryonic stem cell self-renewal and reprogramming
Authors: Percharde Michelle , Lavial Fabrice , Ng Jia-Hui , Kumar Vibhor , Tomaz Rute A. , Martin Nadine , Yeo Jia-Chi , Gil Jesús , Prabhakar Shyam , Ng Huck-Hui , Parker Malcolm G. , Azuara Véronique
Published: September 2012

Embryonic stem cell (ESC) pluripotency depends on a well-characterized gene regulatory network centered on Oct4, Sox2, and Nanog. In contrast, little is known about the identity of the key coregulators and the mechanisms by which they may potentiate transcription in ESCs. Alongside core transcription factors, the orphan nuclear receptor Esrrb (estrogen-related receptor β) is vital for the maintenance of ESC identity and furthermore is uniquely associated with the basal transcription machinery. Here, we show that Ncoa3, an essential coactivator, is required to mediate Esrrb function in ESCs. Ncoa3 interacts with Esrrb via its ligand-binding domain and bridges Esrrb to RNA polymerase II complexes. Functionally, Ncoa3 is critical for both the induction and maintenance of pluripotency. Through chromatin immunoprecipitation (ChIP) sequencing and microarray experiments, we further demonstrate that Ncoa3 shares overlapping gene regulatory functions with Esrrb and cooperates genome-wide with the Oct4–Sox2–Nanog circuitry at active enhancers to up-regulate genes involved in self-renewal and pluripotency. We propose an integrated model of transcriptional and coactivator control, mediated by Ncoa3, for the maintenance of ESC self-renewal and somatic cell reprogramming.
G Protein–Coupled Receptor-Type G Proteins Are Required for Light-Dependent Seedling Growth and Fertility inArabidopsis
Authors: Jaffé Felix W. , Freschet Gian-Enrico C. , Valdes Billy M. , Runions John , Terry Matthew J. , Williams Lorraine E.
Published: September 2012

G protein–coupled receptor-type G proteins (GTGs) are highly conserved membrane proteins in plants, animals, and fungi that have eight to nine predicted transmembrane domains. They have been classified as G protein–coupled receptor-type G proteins that function as abscisic acid (ABA) receptors in Arabidopsis thaliana. We cloned Arabidopsis GTG1 and GTG2 and isolated new T-DNA insertion alleles of GTG1 and GTG2 in both Wassilewskija and Columbia backgrounds. These gtg1 gtg2 double mutants show defects in fertility, hypocotyl and root growth, and responses to light and sugars. Histological studies of shoot tissue reveal cellular distortions that are particularly evident in the epidermal layer. Stable expression of GTG1pro:GTG1-GFP (for green fluorescent protein) in Arabidopsis and transient expression in tobacco (Nicotiana tabacum) indicate that GTG1 is localized primarily to Golgi bodies and to the endoplasmic reticulum. Microarray analysis comparing gene expression profiles in the wild type and double mutant revealed differences in expression of genes important for cell wall function, hormone response, and amino acid metabolism. The double mutants isolated here respond normally to ABA in seed germination assays, root growth inhibition, and gene expression analysis. These results are inconsistent with their proposed role as ABA receptors but demonstrate that GTGs are fundamentally important for plant growth and development.
Two Interacting Proteins Are Necessary for the Editing of the NdhD-1 Site in Arabidopsis Plastids
Authors: Boussardon Clément , Salone Véronique , Avon Alexandra , Berthomé Richard , Hammani Kamel , Okuda Kenji , Shikanai Toshiharu , Small Ian , Lurin Claire
Published: September 2012

After transcription, mRNA editing in angiosperm chloroplasts and mitochondria results in the conversion of cytidine to uridine by deamination. Analysis of Arabidopsis thaliana mutants affected in RNA editing have shown that many pentatricopeptide repeat proteins (PPRs) are required for specific cytidine deamination events. PPR proteins have been shown to be sequence-specific RNA binding proteins allowing the recognition of the C to be edited. The C-terminal DYW domain present in many editing factors has been proposed to catalyze C deamination, as it shows sequence similarities with cytidine deaminases in other organisms. However, many editing factors, such as the first to be discovered, CHLORORESPIRATORY REDUCTION4 (CRR4), lack this domain, so its importance has been unclear. Using a reverse genetic approach, we identified DYW1, an RNA editing factor acting specifically on the plastid ndhD-1 editing site recognized by CRR4. Unlike other known editing factors, DYW1 contains no identifiable PPR motifs but does contain a clear DYW domain. We were able to show interaction between CRR4 and DYW1 by bimolecular fluorescence complementation and to reconstitute a functional chimeric CRR4-DYW1 protein complementing the crr4 dyw1double mutant. We propose that CRR4 and DYW1 act together to edit the ndhD-1 site.
Failure of the Tomato Trans-Acting Short Interfering RNA Program to Regulate AUXIN RESPONSE FACTOR3 and ARF4 Underlies the Wiry Leaf Syndrome
Authors: Yifhar Tamar , Pekker Irena , Peled Dror , Friedlander Gilgi , Pistunov Anna , Sabban Moti , Wachsman Guy , Alvarez John Paul , Amsellem Ziva , Eshed Yuval
Published: September 2012

Interfering with small RNA production is a common strategy of plant viruses. A unique class of small RNAs that require microRNA and short interfering (siRNA) biogenesis for their production is termed trans-acting short interfering RNAs (ta-siRNAs). Tomato (Solanum lycopersicum) wiry mutants represent a class of phenotype that mimics viral infection symptoms, including shoestring leaves that lack leaf blade expansion. Here, we show that four WIRY genes are involved in siRNA biogenesis, and in their corresponding mutants, levels of ta-siRNAs that regulate AUXIN RESPONSE FACTOR3 (ARF3) and ARF4 are reduced, while levels of their target ARFs are elevated. Reducing activity of both ARF3 and ARF4 can rescue the wiry leaf lamina, and increased activity of either can phenocopy wiry leaves. Thus, a failure to negatively regulate these ARFs underlies tomato shoestring leaves. Overexpression of these ARFs in Arabidopsis thaliana, tobacco (Nicotiana tabacum), and potato (Solanum tuberosum) failed to produce wiry leaves, suggesting that the dramatic response in tomato is exceptional. As negative regulation of orthologs of these ARFs by ta-siRNA is common to land plants, we propose that ta-siRNA levels serve as universal sensors for interference with small RNA biogenesis, and changes in their levels direct species-specific responses.
Mutations in the Arabidopsis H3K4me2/3 Demethylase JMJ14 Suppress Posttranscriptional Gene Silencing by Decreasing Transgene Transcription
Authors: Le Masson Ivan , Jauvion Vincent , Bouteiller Nathalie , Rivard Maud , Elmayan Taline , Vaucheret Hervé
Published: September 2012

Posttranscriptional gene silencing (PTGS) mediated by sense transgenes (S-PTGS) results in RNA degradation and DNA methylation of the transcribed region. Through a forward genetic screen, a mutant defective in the Histone3 Lysine4 di/trimethyl (H3K4me2/3) demethylase Jumonji-C (JmjC) domain-containing protein14 (JMJ14) was identified. This mutant reactivates various transgenes silenced by S-PTGS and shows reduced Histone3 Lysine9 Lysine14 acetylation (H3K9K14Ac) levels, reduced polymerase II occupancy, reduced transgene transcription, and increased DNA methylation in the promoter region, consistent with the hypothesis that high levels of transcription are required to trigger S-PTGS. The jmj14 mutation also reduces the expression of transgenes that do not trigger S-PTGS. Moreover, expression of transgenes that undergo S-PTGS in a wild-type background is reduced in jmj14 sgs3 double mutants compared with PTGS-deficient sgs3 mutants, indicating that JMJ14 is required for high levels of transcription in a PTGS-independent manner. Whereas endogenous loci regulated by JMJ14 exhibit increased H3K4me2 and H3K4me3 levels in the jmj14 mutant, transgene loci exhibit unchanged H3K4me2 and decreased H3K4me3 levels. Because jmj14 mutations impair PTGS of transgenes expressed under various plant or viral promoters, we hypothesize that JMJ14 demethylation activity is prevented by antagonistic epigenetic marks specifically imposed at transgene loci. Removing JMJ14 likely allows other H3K4 demethylases encoded by the Arabidopsis thaliana genome to act on transgenes and reduce transcription levels, thus preventing the triggering of S-PTGS.
Essential Role of VIPP1 in Chloroplast Envelope Maintenance in Arabidopsis
Authors: Zhang Lingang , Kato Yusuke , Otters Stephanie , Vothknecht Ute C. , Sakamoto Wataru
Published: September 2012

VESICLE-INDUCING PROTEIN IN PLASTIDS1 (VIPP1), proposed to play a role in thylakoid biogenesis, is conserved in photosynthetic organisms and is closely related to Phage Shock Protein A (PspA), which is involved in plasma membrane integrity in Escherichia coli. This study showed that chloroplasts/plastids in Arabidopsis thaliana vipp1 knockdown and knockout mutants exhibit a unique morphology, forming balloon-like structures. This altered morphology, as well as lethality of vipp1, was complemented by expression of VIPP1 fused to green fluorescent protein (VIPP1-GFP). Several lines of evidence show that the balloon chloroplasts result from chloroplast swelling related to osmotic stress, implicating VIPP1 in the maintenance of plastid envelopes. In support of this, Arabidopsis VIPP1 rescued defective proton leakage in an E. coli pspA mutant. Microscopy observation of VIPP1-GFP in transgenic Arabidopsis revealed that VIPP1 forms large macrostructures that are integrated into various morphologies along the envelopes. Furthermore, live imaging revealed that VIPP1-GFP is highly mobile when chloroplasts are subjected to osmotic stress. VIPP1-GFP showed dynamic movement in the transparent area of spherical chloroplasts, as the fluorescent molecules formed filament-like structures likely derived from disassembly of the large VIPP1 complex. Collectively, our data demonstrate that VIPP1 is a multifunctional protein in chloroplasts that is critically important for envelope maintenance.
New business models for creating shared value
Authors: Michelini Laura , Fiorentino Daniela
Published: September 2012

Purpose

For a long time, managing the relationship between business and society has been one of the main topics of academic and business literature. Porter and Kramer have proposed a new interpretation of this relationship based on the mutual dependence that exists between corporations and society. Trying to put into practice the shared value principle, for‐profit companies engaging in strategic CSR have chosen to implement new hybrid business models. These models include the social business model and the inclusive business model. The purpose of the paper is to understand which characteristics distinguish social and inclusive business models and what kind of benefits and risks (for companies and for communities) are connected to each model.

Design/methodology/approach

In order to identify the features of the inclusive business and social business models and the benefits and risks associated with these models, ten case studies were analyzed. Analysis of the business models was based on a theoretical framework developed through the analysis of the literature.

Findings

The findings of the research suggest two main conclusions. First, social and inclusive business models are similar in partner networks, use of knowledge and value chain, in the development of innovative distribution models (except for the cases in which the market considered is not in an emerging country) and in terms of social benefit. Second, the social and inclusive business models are different in terms of value proposition, governance systems, profits management model, social risks and economic profit equation.

Research limitations/implications

The first limitation is that the case study analysis is based on documentary materials; for further investigation it might be useful to develop in‐depth interviews with key figures involved in the implementation of business models. Even though this descriptive study has allowed a first important step in taking a comparative analysis between the two business models, further research should strive to extend the analysis to all the hybrid business models that are being developed with the aim of creating shared value.

Practical implications

The final propositions allow entrepreneurs and managers to better understand the characteristics of business models. Moreover, the theoretical framework is a conceptual instrument that is useful in analyzing and evaluating alternative ways to develop new business models – based on the “creating shared value” principle – in developing markets.

Originality/value

The paper focuses on comparing the characteristics of the social versus inclusive business models. Studies that compare business models in the social venturing space are limited. Moreover, the study addresses the similarity and differences between the two business models rather than focusing on the two models separately as the previous researches have done.
Cause and effect between FII trading behaviour and stock market returns
Authors: Chandra Abhijeet
Published: September 2012

Purpose

The purpose of this paper is to examine the direction of causality between foreign institutional investment (FII) trading volume and stock market returns in the Indian context. There is evidence of uni‐directional causalities from stock returns to FII flows across various sample periods. The paper attempts to establish whether net FII trading volume causes variations in stock market returns or vice versa.

Design/methodology/approach

Using daily data on three different measures of FII trading volume as proxy for FII trading behaviour and S&P CNX Nifty returns, Granger‐causality approach is applied to investigate the bi‐directional causality between net FII trades and returns.

Findings

Bi‐directional causality between net FII investment and Indian stock market return is observed. In general, the FIIs seem to be chasing the Indian stock market returns. It is found that FII trading behaviour resulting in heavy trading volumes may cause variations in stock market returns only in the very short‐term, but afterwards, it is the stock market returns which cause changes in FII trading behaviour.

Research limitations/implications

Since foreign equity investors monitor the movement of stock prices, and furthermore, the role of FIIs' exerting impact on Indian stock markets tends to be growing, the authorities will have to develop an environment where FIIs would maintain their positions with confidence, thereby making the markets, as well as investments, more stable. This research considered only stock market returns to test its relationship with three measures of FII trading volume; more macroeconomic as well as microeconomic variables may further be considered for the purpose.

Originality/value

The paper contributes some empirical evidence using three different measures of FII trading volume as proxy of FII trading behaviour, and its bi‐directional relationship with Indian stock market returns.
Commentary: How Ethanol Short‐Circuits the Cerebellum—Actions on Golgi Cells in Freely—Moving Animals
Authors: Freund Ronald K.
Published: September 2012

This commentary discusses the important contributions of the article published in this journal by Huang and colleagues, titled, “Acute ethanol exposure increases firing and induces oscillations in cerebellar Golgi cells of freely moving rats.” In this manuscript, Huang and colleagues present a number of interesting and important findings. While it has been shown previously that ethanol (EtOH) causes an increase in the firing of cerebellar Golgi cells in brain slice preparations and anesthetized animals, here the authors provide the first evidence that this action of EtOH occurs in vivo in freely moving, unanesthetized animals. These results also enhance our understanding of cerebellar functioning by describing the mechanism by which EtOH essentially de‐afferentates (blocks specific inputs to) the cerebellum from the normal processing of sensory signals due to EtOH‐induced Golgi neuron excitation, resulting in inhibition of granule cells. Furthermore, the authors characterize the novel observation of EtOH‐induced neuronal oscillations, which was not previously observed in other preparations.
Evaluation of the adult patient with atopic dermatitis
Authors: de Bruin Weller M. S. , Rockmann H. , Knulst A. C. , Bruijnzeel‐Koomen C. A. F. M.
Published: September 2012

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a large impact on quality of life of the patients and their families. In most cases, the diagnosis of AD can easily be made based on (family) history and clinical examination. If necessary, a practical set of diagnostic criteria such as the UK diagnostic criteria can be used. During the diagnostic phase, it is important to pay attention to atopic comorbidity, such as allergic airway disease (allergic asthma and/or rhinitis), allergic eye disease (atopic (kerato) conjunctivitis) and immediate‐type food allergy. This will not have direct consequences for the treatment of AD, but may be important for the overall well‐being of the patient. Psychological factors, such as family circumstances, work/school performance and lifestyle factors should also be explored. Severity scoring using properly validated scoring lists may not be necessary for the diagnosis, however, is recommended for monitoring therapy. Simple scoring systems, such as TIS and IGA are easy to perform in daily practice. Several flare factors in AD, such as exposure to irritants or UV light, can be identified by history and clinical examination: in individual cases, additional diagnostic tests may sometimes be useful to confirm clinical suspicion. There is only limited evidence that allergen exposure to aeroallergens and/or food allergens influences AD severity. Therefore, routine allergen testing is not necessary for diagnosis and treatment of AD. The decision to perform allergen tests mainly depends on atopic comorbidity.
The Association Between Asthma and Helicobacter pylori: A Meta‐Analysis
Authors: Wang Qiang , Yu Chaoran , Sun Yi
Published: September 2012

Objective

The severity and incidence of asthma have increased drastically in the developed nations of the world over the last decades. Currently, some evidences indicate an inverse association between Helicobacter pylori and asthma, but some studies did not get the same conclusion. To make this question clear, we systematically reviewed the published evidence for an association between H. pylori infection and asthma.

Methods

Medline and SCI databases up to April 2012 were searched to identify studies that evaluated the association between H. pylori and asthma. Relevant publications were searched using the following keywords or synonyms: asthma or Helicobacter pylori. Methodologic quality was scored by using a standardized list of criteria, and meta‐analysis was conducted to calculate crude odds ratios (ORs) with 95% confidence intervals (CIs).

Results

Nineteen studies met our inclusion criteria: nine cross‐sectional studies, seven case–control studies, and three prospective cohort studies. The overall methodologic quality score was high. Pooled ORs for the association between asthma and H. pylori infection were 0.84 (95% CI: 0.74–0.96) in nine cross‐sectional studies, 0.94 (95% CI: 0.79–1.12) in seven case–control studies, and 0.82 (95% CI: 0.53–1.27) in three cohort studies. The pooled OR for all included studies was 0.81 (95% CI: 0.72–0.91) in children and 0.88 (95% CI: 0.71–1.08) in adults.

Conclusions

We found a weak evidence for an inverse association between asthma and H. pylori infection both in children and in adults.
Clinical pharmacological properties of mipomersen (Kynamro), a second generation antisense inhibitor of apolipoprotein B
Authors: Crooke Stanley T. , Geary Richard S.
Published: September 2012

Mipomersen is a second generation antisense oligonucleotide that targets apolipoprotein B. It has been studied thoroughly in clinical trials (more than 800 subjects), including four randomized double‐blind placebo controlled phase 3 studies involving 391 patients, and is in registration for the treatment of severe hypercholesterolaemia. The pharmacokinetic and pharmacodynamic properties of mipomersen are well characterized. Mipomersen is rapidly and extensively absorbed after subcutaneous administration and has an elimination half‐life of approximately 30 days across species. It is cleared by nuclease metabolism and renal excretion of the metabolites. Mipomersen reduces all apolipoprotein B containing atherogenic particles and displays dose dependent reductions between 50–400 mg week−1, both as a single agent and in the presence of maximal lipid lowering therapy. No drug–drug interactions have been identified. Mipomersen is a representative of second generation antisense drugs, all of which have similar properties, and is thus representative of the behaviour of the class of drugs.
Technetium‐99 conjugated with methylene diphosphonate inhibits receptor activator of nuclear factor‐κB ligand‐induced osteoclastogenesis
Authors: Gong Wei , Dou Huan , Liu Xianqin , Sun Lingyun , Hou Yayi
Published: September 2012

In the present study, we investigated the effects of technetium‐99 conjugated with methylene diphosphonate (99Tc‐MDP), an agent used in radionuclide therapy, on receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis and explored the underlying mechanisms.

The murine macrophage cell line RAW264.7 and bone marrow‐derived‐macrophages from C57BL/6 mice (BMM) were used as models for osteoclastogenesis in vitro. The expression of some key factors in RANKL (50 ng/mL)‐induced osteoclastogenesis in RAW264.7 cells was investigated by flow cytometry and real‐time reverse transcription–polymerase chain reaction (RT‐PCR). To detect multinucleated osteoclast formation, RAW264.7 cells were induced with RANKL for 4 days, whereas BMM were induced by 50 ng/mL RANKL and 20 ng/mL macrophage colony‐stimulating factor for 7 days, before being stained with tartrate‐resistant acid phosphatase.

Osteoclastogenesis was evaluated using the osteoclast markers CD51, matrix metalloproteinase (MMP)‐9 and cathepsin K. At 0.01 μg/mL, 99Tc‐MDP significantly inhibited RANKL‐induced osteoclastogenesis without any cytotoxicity. In addition, 99Tc‐MDP abolished the appearance of multinucleated osteoclasts.

Real‐time RT‐PCR analysis of transcription factor expression revealed that 99Tc‐MDP inhibited the expression of c‐Fos and nuclear factor of activated T cells. In addition, 99Tc‐MDP inhibited the expression of the inflammatory factors interleukin (IL)‐6, tumour necrosis factor‐α and IL‐1β. Finally, 99Tc‐MDP inhibited the activation of mitogen‐activated protein kinases in RAW264.7 cells following RANKL stimulation.

In conclusion, 99Tc‐MDP possesses anti‐osteoclastogenic activity against RANKL‐induced osteoclast formation.
Biotic acceptance in introduced amphibians and reptiles in Europe and North America
Authors: Poessel Sharon A. , Beard Karen H. , Callahan Colin M. , Ferreira Rodrigo B. , Stevenson Erika T.
Published: September 2012

Aim

The biotic resistance hypothesis argues that complex plant and animal communities are more resistant to invasion than simpler communities. Conversely, the biotic acceptance hypothesis states that non‐native and native species richness are positively related. Most tests of these hypotheses at continental scales, typically conducted on plants, have found support for biotic acceptance. We tested these hypotheses on both amphibians and reptiles across Europe and North America.

Location

Continental countries in Europe and states/provinces in North America.

Methods

We used multiple linear regression models to determine which factors predicted successful establishment of amphibians and reptiles in Europe and North America, and additional models to determine which factors predicted native species richness.

Results

Successful establishment of amphibians and reptiles in Europe and reptiles in North America was positively related to native species richness. We found higher numbers of successful amphibian species in Europe than in North America. Potential evapotranspiration (PET) was positively related to non‐native species richness for amphibians and reptiles in Europe and reptiles in North America. PET was also the primary factor determining native species richness for both amphibians and reptiles in Europe and North America.

Main conclusions

We found support for the biotic acceptance hypothesis for amphibians and reptiles in Europe and reptiles in North America, suggesting that the presence of native amphibian and reptile species generally indicates good habitat for non‐native species. Our data suggest that the greater number of established amphibians per native amphibians in Europe than in North America might be explained by more introductions in Europe or climate‐matching of the invaders. Areas with high native species richness should be the focus of control and management efforts, especially considering that non‐native species located in areas with a high number of natives can have a large impact on biological diversity.
Towards a more mechanistic understanding of traits and range sizes
Authors: Laube Irina , Korntheuer Heiko , Schwager Monika , Trautmann Sven , Rahbek Carsten , Böhning‐Gaese Katrin
Published: September 2012

Aim

An important, unresolved question in macroecology is to understand the immense inter‐specific variation in geographic range sizes. While species traits such as fecundity or body size are thought to affect range sizes, a general understanding on how multiple traits jointly influence them is missing. Here, we test the influence of a multitude of species traits on global range sizes ofEuropean passerine birds in order to better understand possible mechanisms behind macroecological relationships.

Location

Global.

Methods

We evaluated the effect of life‐history traits (fecundity, dispersal ability), ecological traits (habitat niche, diet niche, migratory behaviour, migratory flexibility) and a morphological trait (body size) on the global range sizes of 165European passerines. We identified hypotheses from the literature relating traits to range size and used path analysis to test them.

Results

Fecundity, dispersal ability and habitat niche breadth had a direct positive effect on range size. Diet niche position had a direct negative effect on range size. Habitat niche breadth also had an indirect positive effect via higher fecundity. Migratory behaviour had an indirect positive effect via better dispersal ability. Body size had a strong positive direct effect which was reduced by negative indirect effects via several other traits.

Main conclusions

Geographic range sizes ofEuropean passerines were influenced by life‐history traits (fecundity and dispersal ability), ecological traits (habitat niche breadth, diet niche position and migratory behaviour) and by body size. Traits influenced range size both directly and indirectly. Body size effects were particularly complex, with positive and negative effects acting over different pathways. We show that it is necessary to disentangle the direct and indirect influence of multiple traits on range size to better elucidate the mechanisms that generate macroecological relationships.
In search of the cancer candidate: can lay epidemiology help?
Authors: Macdonald Sara , Watt Graham , Macleod Una
Published: September 2012

First published in 1991, the ideas embedded in ‘Lay epidemiology and the prevention paradox’ offered a novel and rational explanation for the lay public’s failure to fully engage with the lifestyle messages offered by health educators. During the course of a large ethnographic study in South Wales, Davison and colleagues described the emergence of what they termed the coronary candidate. Candidacy provides a ‘cultural mechanism’ that facilitates the estimation of risk for coronary heart disease. The model has rarely been applied to other major illnesses. This article presents findings from a study that sought to explore the lay epidemiology model, candidacy and cancer. In a series of in‐depth individual interviews, members of the lay public discussed their ideas about cancer, and what emerged was an explanatory hierarchy to account for cancer events. Yet the random and unpredictable nature of cancer was emphasised as well as a general reluctance to accept the idea of cancer candidacy.
Inviting pain? Pain, dualism and embodiment in narratives of self‐injury
Authors: Chandler Amy
Published: September 2012

The role of pain in the practice of self‐injury is not straightforward. Existing accounts suggest that self‐injury does not cause ‘physical’ pain, however self‐injury is also said to alleviate ‘emotional’ pain by inflicting ‘physical’ pain. This article explores these tensions using sociological theories regarding the socio‐cultural and subjective nature of pain. Analysis derives from in‐depth, life‐story interviews carried out in the UK with people who had self‐injured. Findings contribute to on‐going debates within social science regarding the nature of pain. Participants’ narratives about pain and self‐injury both drew on and challenged dualistic models of embodiment. I suggest that self‐injury offers a unique case on which to extend existing theoretical work, which has tended to focus on pain as an unwanted and uninvited entity. In contrast, accounts of self‐injury can feature pain as a central aspect of the practice, voluntarily invited into lived experience.
Restoring the Narrative of American Environmentalism
Authors: Minteer Ben A. , Pyne Stephen J.
Published: September 2012

The conventional narrative of American environmentalism is no longer very helpful for conservationists and restorationists seeking philosophical justification and guidance for their work. The tradition has often been cropped into a narrower and simplified account of the battle between the philosophies of wise use and preservation, a move bolstered by the turn to historical images of President Teddy Roosevelt and John Muir visiting California's Yosemite National Park in the early years of the twentieth century. This cropped conservation picture needs to be restored and widened to engage the pragmatism that has always been a part of the U.S. environmental tradition, but that became eclipsed by preservationist ideology with the rise of the fields of environmental history and environmental philosophy in the late twentieth century. Restoring this lost pragmatism to the environmental tradition will prove vital to recovering the value of environmental history and philosophy for conservation and restoration practice and to reclaiming a more holistic and useful narrative of people, culture, and environment.
Duplication of the sodium channel gene cluster on 2q24 in children with early onset epilepsy
Authors: Goeggel Simonetti Barbara , Rieubland Claudine , Courage Carolina , Strozzi Susi , Tschumi Sibylle , Gallati Sabina , Lemke Johannes R.
Published: September 2012

Purpose:  Sodium channel gene aberrations are associated with a wide range of seizure disorders, particularly Dravet syndrome. They usually consist of missense or truncating gene mutations or deletions. Duplications involving multiple genes encoding for different sodium channels are not widely known. This article summarizes the clinical, radiologic, and genetic features of patients with 2q24 duplication involving the sodium channel gene cluster.

Methods:  A systematic review of the literature and report of two cases.

Key Findings:  Nine individuals with 2q24 duplication involving the sodium channel gene cluster are described (seven female, two male). All presented with severe seizures refractory to anticonvulsant drugs. Seizure onset was in the neonatal period in eight patients with SCN1A‐involvement, in infancy in one patient with SCN2A and SCN3A, but no SCN1A involvement. Seizure activity decreased and eventually stopped at 5–20 months of age. Seizures recurred at the age of 3 years in the patient with SCN2A and SCN3A, but no SCN1A involvement. Eight patients had a poor neurodevelopmental outcome despite seizure freedom.

Significance:  This article describes a distinct seizure disorder associated with a duplication of the sodium gene cluster on 2q24 described in otherwise healthy neonates and infants with severe, anticonvulsant refractory seizures and poor developmental outcome despite seizure freedom occurring at the age of 5–20 months.