bluuebunny/crossref_metadata_2025 huggingface dataset:
Drosophila BEACH domain autophagic adaptorblue cheeseshuttles between vesicle populations and is required for an early step in autophagy
Authors: Sim Joan , Osborne Kathleen A. , Garcia Irene Argudo , Matysik Artur S. , Kraut Rachel
Published: November 2016

Drosophila melanogaster blue cheese(bchs) encodes a large BEACH (Beige and Chediak-Higashi) family protein that is postulated to function as an adaptor protein with roles in vesicle trafficking. Mutation inbchsleads to the accumulation of ubiquitinated aggregates in aged brains, presumably because of a conserved function with its human homologue Autophagy-Linked FYVE (ALFY), which interacts with Atg5 and p62 to promote the clearance of aggregate-prone proteins. In this study, we present pharmacological and genetic evidence using a well-defined larval motorneuron paradigm that inDrosophila bchsmutants, autophagic deficit contributes to neurodegeneration. Specifically, we show that motorneuron death in larvae is accompanied by the accumulation of prominent ubiquitinated aggregates in synaptic termini, and that these are sensitive to autophagy modulating drugs. In primarybchsneurons, early autophagic compartments increase in number and intensity based on Atg5 expression, but fail to progress to Atg8-labelled compartments, indicating non-clearance. A rescuing transgene encoding the longest Bchs BEACH domain isoform not only reverses this defect, but also greatly increases Atg8 compartment number and rescues neuronal death. Although only a small fraction of Bchs colocalizes with these markers under wild-type conditions, the population of Bchs that does associate with autophagosomes shuttles between different locations depending on how autophagy is induced. These observations, together with epistatic relationships betweenbchsmutant alleles and autophagy-modulating drugs and genetic backgrounds, points to a model whereby BEACH domain isoforms of Bchs participate in the early steps of autophagy by recruiting Atg5 to target substrates for clearance, and that Bchs’ association with different parts of the autophagy machinery depends upon the type of autophagic stress imposed upon the neuron.
A modification-specific peptide-based immunization approach using CRM197 carrier protein:Development of a selective vaccine against pyroglutamate Aβ peptides
Authors: Vingtdeux Valérie , Zhao Haitian , Chandakkar Pallavi , Acker Christopher M. , Davies Peter , Marambaud Philippe
Published: November 2016

Strategies aimed at reducing cerebral accumulation of the amyloid-β (Aβ) peptides have therapeutic potential in Alzheimer’s disease (AD). Aβ immunization has proven to be effective at promoting Aβ clearance in animal models but adverse effects have hampered its clinical evaluation. The first anti-Aβ immunization clinical trial, which assessed a full-length Aβ1-42 vaccine, increased the risk of encephalitis most likely because of autoimmune pro-inflammatory T helper 1 (Th1) response against all forms of Aβ. Immunization against less abundant but potentially more pathologically relevant Aβ products, such as N-terminally-truncated pyroglutamate-3 Aβ (AβpE3), could provide efficacy and improve tolerability in Aβ immunotherapy. Here, we describe a selective vaccine against AβpE3 using the diphtheria toxin mutant CRM197 as carrier protein for epitope presentation. CRM197 is currently used in licensed vaccines and has demonstrated excellent immunogenicity and safety in humans. In mice, our AβpE3:CRM197 vaccine triggered the production of specific anti-AβpE3 antibodies that did not cross-react with Aβ1-42, non-cyclized AβE3, or N-terminally-truncated pyroglutamate-11 Aβ (AβpE11). AβpE3:CRM197 antiserum strongly labeled AβpE3 in insoluble protein extracts and decorated cortical amyloid plaques in human AD brains. Anti-AβpE3 antibodies were almost exclusively of the IgG1 isotype, suggesting an anti-inflammatory Th2 response bias to the AβpE3:CRM197 vaccine. To the best of our knowledge, this study shows for the first time that CRM197 has potential as a safe and suitable vaccine carrier for active and selective immunization against specific protein sequence modifications or conformations, such as AβpE3.
Structural connectome topology relates to regional BOLD signal dynamics in the mouse brain
Authors: Sethi Sarab S. , Zerbi Valerio , Wenderoth Nicole , Fornito Alex , Fulcher Ben D.
Published: November 2016

Brain dynamics are thought to unfold on a network determined by the pattern of axonal connections linking pairs of neuronal populations; the so-called connectome. Prior work has indicated that structural brain connectivity constrains pairwise correlations in brain dynamics (also called functional connectivity), but it is not known whether inter-regional axonal connectivity is related to the intrinsic dynamics of individual brain areas. Here we investigate this relationship using a weighted, directed mesoscale mouse connectome from the Allen Mouse Brain Connectivity Atlas and resting state functional MRI (rs-fMRI) time-series data measured in 184 brain regions in eighteen anesthetized mice. For each brain region, we measured degree, betweenness, and clustering coefficient from weighted and unweighted, and directed and undirected versions of the connectome. We then characterized the univariate rs-fMRI dynamics at each brain region by computing 6 930 time-series properties using the time-series analysis toolbox,hctsa. After correcting for regional volume variations, strong and robust correlations between structural connectivity properties and rs-fMRI dynamics were found only when edge weights were accounted for, and were associated with variations in the autocorrelation properties of the rs-fMRI signal. The strongest relationships were found for weighted in-degree, which was positively correlated to the autocorrelation of fMRI time series at time lagτ= 34s (partial Spearman correlationρ= 0.58), as well as a range of related measures such as relative high frequency power (f> 0.4 Hz:ρ= −0.43). Our results indicate that the topology of inter-regional axonal connections of the mouse brain is closely related to intrinsic, spontaneous dynamics such that regions with a greater aggregate strength of incoming projections display longer timescales of activity fluctuations.
Phase-coherence classification: a new wavelet-based method to separate local field potentials into local (in)coherent and volume-conducted components
Authors: von Papen M. , Dafsari H. , Florin E. , Gerick F. , Timmermann L. , Saur J.
Published: November 2016

Local field potentials (LFP) reflect the integrated electrophysiological activity of a large group of neurons. To minimize influence of external activity on the analysis, conventionally bipolar recordings are used to eliminate volume-conducted signals. Here we introduce a novel method, called phase-coherence classification (PCC), to separate LFP in time-frequency domain into a volume-conducted, a local incoherent and local coherent signal. The PCC allows to compute the power spectral densities of each signal and to associate each class with possible locations of electro-physiological activity. In order to test the resolution properties and accuracy of the method we generate composite and non-stationary synthetic time series with similar statistical characteristics as measured LFP. The PCC identifies volume-conducted signals with a phase threshold that is determined from probability density functions of non-phase-shifted synthetic time series. We estimate optimal PCC parameters for the analysis of beta band oscillations in LFP and apply the PCC to a test data set obtained from within the subthalamic nucleus of eight patients with Parkinson’s disease (PD). We show that PCC can identify activity of multiple local clusters during a tremor episode and quantify the relative power of local and volume-conducted signals. We further analyze the electrophysiological response to an apomorphine injection during rest and show that incoherent activity in the low beta band shows a significant medication-induced decrease. We further find significant movement-induced changes on medication of the local coherent signal, which increased during an isometric hold task and decreased during phasic wrist movement. This indicates a different role of incoherent and coherent signals possibly related to physiologically different networks. This new PCC method can potentially also be applied to EEG and MEG data in order to minimize the influence of spatial leakage on power spectra and coherence estimates.
FastSKAT: Sequence kernel association tests for very large sets of markers
Authors: Lumley Thomas , Brody Jennifer , Peloso Gina , Morrison Alanna , Rice Kenneth
Published: November 2016

The Sequence Kernel Association Test (SKAT) is widely used to test for associations between a phenotype and a set of genetic variants, that are usually rare. Evaluating tail probabilities or quantiles of the null distribution for SKAT requires computing the eigenvalues of a matrix related to the genotype covariance between markers. Extracting the full set of eigenvalues of this matrix (ann×nmatrix, fornsubjects) has computational complexity proportional ton3. As SKAT is often used whenn> 104, this step becomes a major bottleneck in its use in practice. We therefore propose fastSKAT, a new computationally-inexpensive but accurate approximations to the tail probabilities, in which theklargest eigenvalues of a weighted genotype covariance matrix or the largest singular values of a weighted genotype matrix are extracted, and a single term based on the Satterthwaite approximation is used for the remaining eigenval-ues. While the method is not particularly sensitive to the choice of k, we also describe how to choose its value, and show how fastSKAT can automatically alert users to the rare cases where the choice may affect results. As well as providing faster implementation of SKAT, the new method also enables entirely new applications of SKAT, that were not possible before; we give examples grouping variants by topologically assisted domains, and comparing chromosome-wide association by class of histone marker.
Pharmaceutical efficacy of human epiphyseal chondrocytes with differential replication numbers for cellular therapy products
Authors: Nasu Michiyo , Takayama Shinichiro , Umezawa Akihiro
Published: November 2016

The cell-based therapy for cartilage or bone requires a large number of cells serial passages of chondrocytes are, therefore, needed. However, fates of expanded chondrocytes from extra fingers remains unclarified. The chondrocytes from human epiphyses morphologically changed from small polygonal cells, to bipolar elongated spindle cells and to large polygonal cells with degeneration at early passages. Gene of type II collagen was expressed in the cells only at a primary culture (Passage 0) and Passage 1 (P1) cells. The nodules by implantation of P0 to P8 cells were composed of cartilage and perichondrium. The cartilage consisted of chondrocytes with round nuclei and type II collagen-positive matrix, and the perichondrium consisted of spindle cells with type I collage-positive matrix. The cartilage and perichondrium developed to bone with marrow cavity through enchondral ossification. Chondrogenesis and osteogenesis by epiphyseal chondrocytes depended on replication number in culture. It is noteworthy to take population doubling level in correlation with pharmaceutical efficacy into consideration when we use chondrocytes for cell-based therapies.
Gentle, fast and effective crystal soaking by acoustic dispensing
Authors: Collins Patrick M , Tsing Ng Jia , Talon Romain , Nekrosiute Karolina , Krojer Tobias , Douangamath Alice , Brandao-Neto Jose , Wright Nathan , Pearce Nicholas M , von Delft Frank
Published: November 2016

Synopsis

A high-throughput method is described for crystal soaking using acoustic droplet ejection, and its effectiveness demonstrated.

Bright light sources, agile robotics, and fast detectors are continually reducing the time it takes to perform an X-ray diffraction experiment, making high throughput experiments more feasible than ever. But this is also pushing the upstream bottleneck towards sample preparation, even for robust and well characterised crystal systems. Crystal soaking is routinely used to generate protein-ligand complex structures, yet protein crystals are often sensitive to changes in solvent composition, and frequently require gentle or careful stepwise soaking techniques, limiting overall throughput. Here, we describe the use of acoustic droplet ejection for soaking of protein crystals with small molecules, and show that it is both gentle on crystals and allows very high throughput, with 1000 unique soaks easily performed in under 10 minutes. In addition to having very low compound consumption (tens of nanolitres per sample), the positional precision of acoustic droplet ejection enables targeted placement of the compound/solvent away from crystals and towards drop edges, allowing for gradual diffusion of solvent across the drop. This ensures both an improvement in reproducibility of X-ray diffraction and an increased solvent tolerance of the crystals, thus enabling higher effective compound soaking concentrations. We detail the technique here with examples from the protein target JMJD2D, a histone lysine demethylase, having roles in cancer and the focus of active structure based drug design efforts.
Phylogenetic analysis suggests joint control of transmission mode in a grass-endophyte symbiosis
Authors: Brown Alexandra , Akçay Erol
Published: November 2016

How symbionts are transmitted between hosts is key to determining whether symbioses evolve to be harmful or beneficial. Vertical transmission favors mutualistic symbionts, and horizontal transmission more virulent ones. Transmission mode evolution itself depends on whether the host or symbiont can respond to selection on transmission mode. When hosts control the transmission mode, vertical transmission should evolve under more restrictive circumstances than when symbionts are in control. We take a phylogenetic approach to determine whether the host, symbiont, or both control transmission mode using the pooid grass-epichloid endophyte symbiosis as a model system. This study is the first to investigate control of transmission mode evolution in a phylogenetic context. We find a signal of host phylogeny but only in conjunction with symbiont identity. This pattern suggests joint control of transmission mode by the host and symbiont. It also suggests that non-genetic or non-conserved symbiont traits may determine whether host traits lead to vertical or horizontal transmission.
Histone code and higher-order chromatin folding: A hypothesis
Authors: Prakash Kirti , Fournier David
Published: November 2016

Histone modifications alone or in combination are thought to modulate chromatin structure and function; a concept termed histone code. By combining evidence from several studies, we investigated if the histone code can play a role in higher-order folding of chromatin. Firstly using genomic data, we analyzed associations between histone modifications at the nucleosome level. We could dissect the composition of individual nucleosomes into five predicted clusters of histone modifications. Secondly, by assembling the raw reads of histone modifications at various length scales, we noticed that the histone mark relationships that exist at nucleosome level tend to be maintained at the higher orders of chromatin folding. Recently, a high-resolution imaging study showed that histone marks belonging to three of the five predicted clusters show structurally distinct and anti-correlated chromatin domains at the level of chromosomes. This made us think that the histone code can have a significant impact in the overall compaction of DNA: at the level of nucleosomes, at the level of genes, and finally at the level of chromosomes. As a result, in this article, we put forward a theory where the histone code drives not only the functionality but also the higher-order folding and compaction of chromatin.
CFOs’ views on corporate financing decisions
Authors: Yatiwelle Koralalage Weerakoon Banda
Published: November 2016

Purpose

The purpose of this paper is to examine the managerial views on the corporate financing practices of firms in the emerging market of Sri Lanka.

Design/methodology/approach

A survey approach was employed using chief financial officers (CFOs) from the top non-financial firms listed on the Colombo Stock Exchange.

Findings

CFOs’ views on corporate financing practices are not fully consistent with the theory: financial hierarchy appears to be more important and firms are less leveraged. Most Sri Lankan CFOs perceive some policy factors as important and theoretically support: volatility of earnings and cash flows, tax advantages of interest deductibility, transaction costs, timing of interest rates, low foreign interest rates and debt equity targets. These factors are high priority in emerging markets but either not important at all or less important in developed markets. Matching debt maturity with the life of assets is equally important in both markets. Most CFOs adhere their financing to the local debt market, while a few firms use foreign debt. CFOs are concerned about earnings per share (EPS) dilution, providing a natural hedge in foreign debt issues, credit ratings, under/overvaluation of stocks and corporate control, whereas they are significantly important in developed markets. Age and education mostly explain the differences.

Research limitations/implications

The study is restricted to large companies in a relatively smaller market. Hence, sample size is relatively small, even though it shows a higher response rate.

Practical implications

The study offers insights for corporate financing decision-makers that could impact on firm value through a shift in emphasis toward capital structure theories.

Originality/value

The paper focuses on corporate financing practices in Sri Lanka in search of emerging market features that could mitigate the gap in the emerging market literature through survey evidence.
How can the tourism industry respond to the global challenges arising from climate change and environmental degradation?
Authors: Nair Vikneswaran , Mohamed Badaruddin , Thomas Toney K.
Published: November 2016

Purpose

The aim of this paper is to critically review the contribution made by this theme issue in responding to the strategic question: “How can the tourism industry respond to the global challenges arising from climate change and environmental degradation?”

Design/methodology/approach

A critical content analysis of the papers selected for the theme issue was undertaken to learn from the best practices globally. This enabled the theme editors to reflect on the rationale for the theme issue question, the starting-point and the editorial process.

Findings

This summary paper highlights the most significant outcomes from the theme issue in terms of the contributions to knowledge and/or professional practice. It also summarizes the implications for management action and applied research arising from the outcomes and best practices based on case studies in Malaysia, Canada and New Zealand. As the main objective of the theme issue was to obtain a general overview of the relationship between tourism and climate change, five general review papers were included to strengthen the research framework.

Research limitations/implications

This paper outlines the challenges and new approaches in dealing with the issue of climate change. Given the economic, social and environmental significance of tourism, coverage of the climate change issue as it relates to tourism is, yet, limited. Given this scenario, the theme issue has contributed to the body of knowledge in this important field.

Originality/value

This paper explores the extent to which the cases presented and the review of various climate change concepts can provide guidance. The approaches and issues discussed in this theme issue could be replicated and applied in countries that are beginning to focus on climate change issues.
Community participation in mitigating marine waste to reduce climatic change in tourism destinations
Authors: Prabhakaran Sudesh , Nair Vikneswaran , Ramachandran Sridar
Published: November 2016

Purpose

Waste in the marine environment has become a serious task to be managed. Uncontrolled dumping creates large amounts of methane gas contributing to greenhouse gas emissions. This conceptual paper focuses on the role of community in waste management activities to reduce carbon emissions in the marine environment. Hence, this paper aims to examine using literature, the various roles of community, types of marine waste and its impact on carbon emissions and climate change.

Design/methodology/approach

The paper is based on evaluation and criticism from previous studies and provides a hypothetical understanding of the human contribution to climate change, and its impacts which will increasingly affect climate change and sustainable tourism.

Findings

The results from this study can be used as a guide for policy makers to help improve community participation and public engagement in efforts to reduce the levels of waste in the marine environment. This is especially critical in rural tourism destinations where the impact of uncontrolled marine waste has serious consequences for the tourism industry.

Originality/value

The paper contributes to a better understanding of the role of community in mitigating waste to attain a higher quality of tourism experience and environmental benefits from emission level reductions.
Anti‐epiphyte defences in the red seaweed Gracilaria vermiculophylla: non‐native algae are better defended than their native conspecifics
Authors: Wang Shasha , Wang Gaoge , Weinberger Florian , Bian Dapeng , Nakaoka Masahiro , Lenz Mark
Published: November 2016

Epibiosis in the marine environment is a stressor that may determine invasion success in introduced species. Previous comparisons showed resistance to epibionts can be higher in non‐native than in resident seaweed species, but we do not know whether it is an intrinsic trait of the non‐natives or it has been acquired during the invasion process. To elucidate this question, a comparison between native and non‐native populations of the same species is needed.

Resistance against two groups of epiphytes was assessed in living thalli and in artificial substrata coated with surface extracts, both gained from four Asian (native) and four European (non‐native) populations of the red alga Gracilaria vermiculophylla. Two diatom species and two filamentous macroalgae were used as micro‐ and macro‐epiphytes, and one of each type was collected in Asia, while the other came from Europe. Laboratory assays were done in both distributional ranges of G. vermiculophylla and in different seasons. We used G. vermiculophylla from four populations in each range and used a fully crossed design with the factors (i) ‘Origin of Gracilaria’, (ii) ‘Origin of epiphytes’, (iii) ‘Season’ and (iv) ‘Solvent used for extraction’.

Both groups of epiphytes, regardless of their origin, attached less to living thalli and to surface extracts from non‐native G. vermiculophylla. Fewer diatoms attached to hexane‐based extracts, while fewer Ceramium filaments settled on extracts gained with dichloromethane.

Synthesis. Our results show for the first time that non‐native individuals of a marine organism are better defended against epiphytes than native conspecifics. Furthermore, we found evidence that at least a part of the defence is based on extractable secondary metabolites. We discuss several mechanisms that could explain the increased resistance to epiphytes in non‐native individuals, including the release from enemies in the non‐native range, which could lead to an increase in algal performance during the invasion process. We suggest that an enhanced defence against epiphytes after introduction is one reason for G. vermiculophylla's invasion success. Our observation may also apply to other basibiont–epibiont and host–enemy systems, including plant–plant, plant–animal and animal–animal interactions, in aquatic environments and could be a key feature of bioinvasions.
Changes in spatial variance during a grassland to shrubland state transition
Authors: Ratajczak Zak , D'Odorico Paolo , Nippert Jesse B. , Collins Scott L. , Brunsell Nathaniel A. , Ravi Sujith
Published: November 2016

State transitions are changes in ecosystem structure and self‐reinforcing feedbacks that are initiated when an exogenous driver variable crosses a threshold. Reversing state transitions is difficult and costly. While some state transitions are relatively rapid, many take years to decades. Outside of theoretical models, very little is known about slower state transitions and how they unfold in time and space.

We quantified changes in spatial variance as a mesic grassland ecosystem shifts to a shrub‐dominated state, using long‐term experiments and simulations that maintain grasslands with annual fires or initiate a state transition to shrub dominance by decreasing fire frequency.

In the experiments, the susceptibility to state transitions varied substantially in space. In the less frequent fire treatment, some plots became shrub‐dominated around year 20 and grass extirpations began in year 25, but a third of the plots were still grass‐dominated in year 37. Variable rates of state transition resulted in increasing spatial variance of grass cover over time, whereas shrub cover variance decreased. In the annually burned treatment, grasses remained dominant and the spatial variance of grass cover declined.

In a separate experiment, less frequent fires were maintained for 23 years and then switched to annual fires. The switch to annual fires occurred shortly after grass variance started to increase and a majority of these plots quickly returned to a grass dominated state.

In simulations, spatial variance remained low and average grass cover was high under frequent fires. If fire frequency decreased below a threshold, the ecosystem transitioned to shrubland, with a transient increase in the spatial variance of grass cover during the transition between states.

Synthesis. Spatial variability in the rate and susceptibility to state transitions is indicative of a system with a patchy spatial structure, high spatial heterogeneity and low connectivity between patches. Increases in spatial variance can serve as an indication that some patches have begun a state transition and that management interventions are needed to avoid widespread transitions. This is one of the first empirical examples where altering management after an increase in spatial variance prevented state transitions.
An assessment of carbon and nutrient limitations in the formation of the southern Andes tree line
Authors: Fajardo Alex , Piper Frida I.
Published: November 2016

Although the principal mechanism determining tree line formation appears to be carbon (C)‐sink limitations due to low temperatures, few studies have assessed the complementary role of reduced soil nutrient availability with elevation. We tested the hypothesis that nutrient (especially nitrogen, N) limitations at tree line may directly (via C‐source) or indirectly (via C‐sink) reduce the growth of a winter deciduous tree line species.

If a shortage of soil N with elevation is involved in tree line formation, it should occur in two alternative ways: (i) through sink limitations because N is required for tissue formation, which would indirectly limit C investments (N decreases and C reserves increase with elevation), and (ii) through C limitations because this would lead directly to a reduction of photoassimilates (N and C reserves decrease with elevation).

In testing our hypothesis, we analysed tree growth rates (basal area increment), twig non‐structural carbohydrate (NSC) and N concentrations, leaf N, phosphorus (P), N:P ratio concentrations, and soil nutrient levels (NO3−, NH4+, Olsen–P) in four disparate climate and soil Nothofagus pumilio tree lines spanning 18 degrees of latitude in the southern Andes of Chile.

We found a significant decrease in tree growth with elevation. Twig NSC concentrations pooled across locations also decreased significantly with elevation (starch constituted most of the NSC and was highly responsible for the negative trend), although this trend was mostly driven by the northernmost locations. Contrary to soil N availability, leaf N and P concentrations increased significantly with elevation. Twig N concentrations, soil P and leaf N:P ratios did not change with elevation.

Synthesis. The elevational decrease in NSC concentrations supports C‐source limitation in N. pumilio trees at tree line elevation. In the light of this, we assert that the current global explanation for tree line formation (C‐sink‐limitation driven by low temperatures) must be revisited. Given that leaf N and P concentrations increased and twig N concentrations did not change with elevation, nutrient limitation is not likely to be involved in the C‐limitations and could not therefore be an explanation for tree line formation.
Formation of propionate and butyrate by the human colonic microbiota
Authors: Louis Petra , Flint Harry J.
Published: November 2016

The human gut microbiota ferments dietary non‐digestible carbohydrates into short‐chain fatty acids (SCFA). These microbial products are utilized by the host and propionate and butyrate in particular exert a range of health‐promoting functions. Here an overview of the metabolic pathways utilized by gut microbes to produce these two SCFA from dietary carbohydrates and from amino acids resulting from protein breakdown is provided. This overview emphasizes the important role played by cross‐feeding of intermediary metabolites (in particular lactate, succinate and 1,2‐propanediol) between different gut bacteria. The ecophysiology, including growth requirements and responses to environmental factors, of major propionate and butyrate producing bacteria are discussed in relation to dietary modulation of these metabolites. A detailed understanding of SCFA metabolism by the gut microbiota is necessary to underpin effective strategies to optimize SCFA supply to the host.
Changing tastes: learning hunger and fullness after gastric bypass surgery
Authors: Hillersdal Line , Christensen Bodil J. , Holm Lotte
Published: November 2016

Gastric bypass surgery is a specific medical technology that alters the body in ways that force patients to fundamentally change their eating habits. When patients enrol for surgery, they enter a learning process, encountering new and at times contested ways of sensing their bodies, tasting, and experiencing hunger and fullness. In this paper, we explore how patients begin to eat again after gastric bypass surgery. The empirical data used here are drawn from a Danish fieldwork study of individuals undergoing obesity surgery. The material presented shows how the patients used instructions on how to eat. We explore the ways in which diverse new experiences and practices of hunger and fullness are part of the process of undergoing surgery for severe obesity. New sensory experiences lead to uncertainty; as a result, patients practice what we term mimetic eating, which reflects a ‘sensory displacement’ and hence a rupture in the person's sense of self and social relations. We suggest that eating should be conceptualised as a practice that extends beyond the boundaries of our bodies and into diverse realms of relations and practices, and that changing the way we eat also changes the fundamentally embodied experience of who we are.
Durable Domestic Dreams: Exploring Homes in Estonian Socialist‐era Summerhouse Settlements
Authors: Nuga Mari , Leetmaa Kadri , Tammaru Tiit
Published: November 2016

‘Home’ and the connotations of this term are little understood in the context of post‐socialist Central and Eastern Europe. While modern suburban living was rather unusual in this region under socialism, more and more people live in suburbia today. This article concerns itself with the homes of residents in the former socialist‐era summerhouse settlements in Estonia. Its aim is to further an understanding of the origins and (dis)continuities of the notion of home for individuals living in a post‐socialist environment. This study is based on ethnographic fieldwork. In this article, we present socialist and post‐socialist housing in context and describe how it has been shaped by changes in society. Our findings show that the homes of informants appear to strengthen their sense of freedom, autonomy and stability, while simultaneously inspiring their dreams and imaginations of home.
The Relation Between Earnings Management and Non‐GAAP Reporting
Authors: Black Ervin L. , Christensen Theodore E. , Taylor Joo T. , Schmardebeck Roy
Published: November 2016

Managers have a variety of tools at their disposal to influence stakeholder perceptions. Earnings management and the strategic reporting of non‐GAAP earnings are just two of the available menu choices. We explore how real earnings management and accruals management influence the probability that a company will disclose a non‐GAAP adjusted earnings metric in its earnings press release and the likelihood that it will do so aggressively. We first investigate situations where managers already meet analysts’ expectations either based on strong operating performance or after employing real and accruals management. We find that when solid operating performance alone allows firms to meet expectations, managers do not employ earnings management or non‐GAAP reporting. However, when managers meet expectations using real and accruals management, they are significantly less likely to report a non‐GAAP earnings metric. Next, we explore scenarios where companies fall short of expectations. We find that when they just miss expectations after managing GAAP earnings, they are significantly more likely to employ non‐GAAP reporting, suggesting that the timing and relatively costless nature of non‐GAAP reporting allows managers to appear to meet expectations on a non‐GAAP basis when managed GAAP earnings fall short. Moreover, we find that companies are more likely to report non‐GAAP earnings (and to do so aggressively) when (i) they are unable to use real or accruals earnings management, (ii) are constrained by prior‐period accruals management, and (iii) their operating performance is poor. Taken together, our results are consistent with a substitute relation between non‐GAAP reporting and both real and accruals management.
The Influence of Mixers Containing Artificial Sweetener or Different Doses of Carbohydrate on Breath Alcohol Responses in Females
Authors: Smith Cassie , Herzig Peter John , Davey Andrew , Desbrow Ben , Irwin Christopher
Published: November 2016

Background

Breath alcohol responses may be affected by the presence of carbohydrate (CHO) in a beverage. This study investigated the impact of consuming alcohol with mixers containing various doses of CHO or an artificial sweetener on breath alcohol concentration (BrAC), ratings of intoxication and impairment, and cognitive performance in females.

Methods

Twenty‐six females (age 25.1 ± 0.7 years, mean ± standard deviation) completed a crossover study involving 4 trials. A dose of alcohol was consumed in each trial mixed with water (W), artificial sweetener (150 ± 1 mg aspartame [AS]), or CHO (15 g sucrose [15CHO] and 50 g sucrose [50CHO]). BrAC was sampled for 210 minutes following beverage ingestion and analyzed for peak BrAC and other parameters using WinNonlin noncompartmental pharmacokinetic modeling (cmax, tmax, area under the curve to the last measured time point [AUClast]). An objective measure of cognitive performance was assessed using a 4‐choice reaction time (CRT) task. Estimation of BrAC, self‐reported ratings of intoxication, and willingness to drive were recorded.

Results

Mean peak BrAC was reduced in a dose–response manner when alcohol was consumed with CHO compared to both W and AS treatments (W: 0.054 ± 0.015%, AS: 0.052 ± 0.011%, 15CHO: 0.049 ± 0.008%, 50CHO: 0.038 ± 0.007%). No difference in peak BrAC was observed between W and AS treatments. WinNonlin parameters revealed significant differences in cmax and AUClast (W: 4.80 ± 1.12 g/dl/h, AS: 4.61 ± 0.92 g/dl/h, 15CHO: 4.10 ± 0.86 g/dl/h, 50CHO: 3.11 ± 0.58 g/dL/h) when CHO‐containing beverages were consumed compared to W and AS treatments. No difference in tmax or CRT was observed between treatments. Participants were able to detect subtle differences in peak BrAC and reported greater ability to drive after consuming 50CHO compared to W. However, participant's willingness to drive and CRT did not differ between treatments.

Conclusions

Consuming alcohol with CHO‐containing mixers attenuates peak BrAC and reduces total alcohol exposure in a dose–response manner compared to drinks containing artificial sweetener or no additives. The effect of adding CHO to alcoholic beverages may translate to reduced risk of alcohol‐related harms.
Mind the gap—a European viewpoint on Alcoholics Anonymous
Authors: Vederhus John‐Kåre
Published: November 2016

Commentary to: Is Alcoholics Anonymous religious, spiritual, neither? Findings from 25 years of mechanisms of behavior change research
Liquidity in Up and Down Markets for Asset Pricing: Evidence from the Taiwan Stock Market
Authors: Shih Yi‐Cheng , Su Xuan‐Qi
Published: November 2016

Using a sample of stocks listed on the Taiwan Stock Exchange during 1991–2014, this study investigates the liquidity in up and down markets, which is important for understanding asset pricing. Firm‐level original Amihud, Journal of Financial Markets, 5, 2002, 31. illiquidity is decomposed into two half‐Amihud measures for up‐ and down‐market days. First, we show that the ability of the down‐market liquidity level to explain the cross‐section of returns subsumes the up‐market liquidity level. Second, only loadings on systematic down‐market liquidity factors are significantly priced. Third, a liquidity risk factor constructed by the down‐market component, rather than the up‐market component significantly explains the time‐series and cross‐sectional variation in returns sorted by firm size, suggesting that the liquidity risk factor associated with down‐market days performs better in capturing the flight‐to‐liquidity. Overall, the findings support the view that the liquidity in down markets plays a more important role in asset pricing than the liquidity in up markets.
Inside Irredentism: A Global Empirical Analysis
Authors: Siroky David S. , Hale Christopher W.
Published: November 2016

Although many countries have ethnic kin on the “wrong side” of their borders, few seek to annex foreign territories on the basis of ethnicity. This article examines why some states pursue irredentism, whereas others exhibit restraint. It focuses on the triadic structure of the kin group in the irredentist state, its coethnic enclave, and the host state, and provides new data on all actual and potential irredentist cases from 1946 to 2014. The results indicate that irredentism is more likely when the kin group is near economic parity with other groups in its own state, which results in status inconsistency and engenders grievances. It is also more likely in more ethnically homogeneous countries with winner‐take‐all majoritarian systems where the kin group does not need to moderate its policy to win elections by attracting other groups. These conditions generate both the grievance and opportunity for kin groups to pursue irredentism.
RHS6 coordinately regulates the Th2 cytokine genes by recruiting GATA3, SATB1, and IRF4
Authors: Hwang S. S. , Jang S. W. , Lee K. O. , Kim H. S. , Lee G. R.
Published: November 2016

Background

Asthma is a Th2 cell‐driven inflammatory disease and a major public health concern. The cis‐acting element Rad50 hypersensitive site 6 (RHS6) in the Th2 locus control region is essential for regulation of the Th2 cytokine genes; however, its role in allergic airway inflammation and underlying molecular mechanisms of the regulation by RHS6 are poorly understood.

Objective

We sought to understand the role of RHS6 in the development of allergic airway inflammation and its molecular mechanism for Th2 cytokine expression.

Methods

We used an ovalbumin‐induced allergic inflammation model with RHS6‐deficient mice to examine the role of RHS6 in this process. To examine molecular mechanism of RHS6 for Th2 cytokine expression, we used DNA affinity chromatography and mass spectrometry, quantitative RT‐PCR, ELISA, intracellular cytokine staining, chromatin immunoprecipitation, and co‐immunoprecipitation.

Results

Deletion of RHS6 caused a dramatic resistance to allergic airway inflammation. RHS6 recruited transcription factors GATA3, SATB1, and IRF4, which play important roles in expression of all three Th2 cytokine genes. RHS6 deficiency caused inhibition of transcription factor‐induced Th2 cytokine gene expression.

Conclusion

RHS6 is a critical regulatory element for allergic airway inflammation and for coordinate regulation of Th2 cytokine genes by recruiting GATA3, SATB1, and IRF4.
Sleep differences in one‐year‐old children were related to obesity risks based on their parents’ weight according to baseline longitudinal study data
Authors: Ekstedt Mirjam , Darkeh Mojgan Haji Seyed Ebrahim , Xiu Lijuan , Forssén Michaela , Johansson Elin , Ek Anna , Svensson Viktoria , Ekbom Kerstin , Marcus Claude
Published: November 2016

Aim

Parental obesity is the predominant risk factor for child obesity. We compared sleep in one‐year‐old children with different obesity risks, based on parental weight, and explored associations with weight, parental sleep and family factors.

Methods

Baseline data from 167 families participating in a longitudinal obesity prevention programme was used. Sleep patterns were compared between groups with high and low obesity risks, based on parental weight, and associations between child sleep and weight status, family obesity risk and parental sleep were explored. Sleep was assessed using child sleep diaries and standard parental questionnaires.

Results

Later bedtime, longer sleep onset latency and lower sleep efficiency were observed among children in the high‐risk group. Child sleep onset latency was associated with the family obesity risk (β = 0.25, p = 0.001), child bedtime with both maternal (β = 0.33, p < 0.01) and paternal bedtime (β = 0.22, p < 0.05) and child sleep efficiency with maternal sleep quality (β = 0.20, p < 0.01). The child's bedtime was weakly associated with their body mass index (β = 0.17, p < 0.05).

Conclusion

Sleep differed between one‐year‐old children with high or low obesity risks, based on their parents’ body mass index, and was associated with the family obesity risk and parental sleep. The child's bedtime was weakly associated with their weight status.
Biology of VO2max: looking under the physiology lamp
Authors: Lundby C. , Montero D. , Joyner M.
Published: November 2016

In this review, we argue that several key features of maximal oxygen uptake (VO2max) should underpin discussions about the biological and reductionist determinants of its interindividual variability: (i) training‐induced increases in VO2max are largely facilitated by expansion of red blood cell volume and an associated improvement in stroke volume, which also adapts independent of changes in red blood cell volume. These general concepts are also informed by cross‐sectional studies in athletes that have very high values for VO2max. Therefore, (ii) variations in VO2max improvements with exercise training are also likely related to variations in these physiological determinants. (iii) All previously untrained individuals will respond to endurance exercise training in terms of improvements in VO2max provided the stimulus exceeds a certain volume and/or intensity. Thus, genetic analysis and/or reductionist studies performed to understand or predict such variations might focus specifically on DNA variants or other molecular phenomena of relevance to these physiological pathways.
Targeting multiple pathways reduces renal and cardiac fibrosis in rats with subtotal nephrectomy followed by coronary ligation
Authors: Oosterhuis N. R. , Bongartz L. G. , Verhaar M. C. , Cheng C. , Xu Y. J. , van Koppen A. , Cramer M. J. , Goldschmeding R. , Gaillard C. A. , Doevendans P. A. , Braam B. , Joles J. A.
Published: November 2016

Aim

Multiple interacting pathways contribute to progression of renal and cardiac damage in chronic kidney disease followed by chronic heart failure (renocardiac syndrome). We hypothesized that simultaneous pharmacological modulation of critical pathways implicated in renocardiac syndrome would effectively reduce fibrosis in and preserve function of heart and kidney.

Methods

Rats were subjected to subtotal nephrectomy followed 9 weeks later by coronary artery ligation. From week 11 until week 16, rats received vehicle or losartan, or a combination of the NF‐kB inhibitor PDTC, the NO donor molsidomine and superoxide dismutase mimetic tempol, or a combination of all four of these plus metoprolol together. At week 16, renal and cardiac structure, function and gene expression were assessed.

Results

Individual and combined treatments were similarly effective in limiting cardiac fibrosis and further decline in systolic function. Combined treatment with all five drugs reduced renal fibrosis and CTGF gene expression more effectively than other strategies. Combining all five drugs reduced heart rate, inotropy and mean arterial pressure (MAP).

Conclusion

Thus, in our model of chronic renocardiac syndrome, combined treatments similarly decreased cardiac fibrosis and stabilized systolic function as losartan alone, perhaps suggesting a dominant role for a single factor such as angiotensin II type 1 (AT1) receptor activation or inflammation in the network of aberrant systems in the heart. However, tubulointerstitial fibrosis was most effectively reduced by a five‐drug regimen, pointing to additive effects of multiple pathophysiological pathways in the kidney.
Validity study of Patient Health Questionnaire‐9 items for Internet screening in depression among Chinese university students
Authors: Du Na , Yu Kexin , Ye Yan , Chen Shulin
Published: November 2016

Background

Internet intervention in Chinese university students would be a possible approach to overcome the gap between high rate of depression and high rates of underdiagnosis and undertreatment. As a popular measure of screening, the feasibility and user satisfaction of Patient Health Questionnaire‐9 items for online program were tested.

Methods

The subjects were enrolled based on an email list from the students' office of a Chinese university, and 300 undergraduate students were randomly invited of which 230 (76.7%) students were willing to participate in the study and completed the first test. After 2 weeks, a subsample of 150 (65.2%) subjects were randomly chosen to retake the test for the test‐retest reliability. And 81 (35.2%) among the 230 subjects were randomly selected to undergo the Mini International Neuropsychiatric Interview within 48 hours. Among 150 subjects, 120 (52.2%) completed client satisfaction questionnaire about this online screening program.

Results

(1) The Cronbach alpha was 0.80 and the test‐retest reliability was 0.78. (2) The optimal cutoff score of 10 revealed a sensitivity of 0.74 and specificity of 0.85, with an area under the curve of 0.897 (95% confidence interval, 0.823‐0.970). (3) The mean duration of administration was 3.5 minutes. (4) Satisfaction with the online screening program was highly appreciated.

Conclusions

The results indicated potential value of the online screening program for further Internet‐administrated programs of depression among Chinese university students.