bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocytosis of Red Blood Cell Microparticles by Pulmonary Endothelial Cells is Mediated By Rab5
Authors: Kim Young , Abplanalp William A. , Jung Andrew D. , Schuster Rebecca M. , Lentsch Alex B. , Gulbins Erich , Caldwell Charles C. , Pritts Timothy A.
Published: September 2017

Microparticles are submicron vesicles shed from aging erythrocytes as a characteristic feature of the red blood cell (RBC) storage lesion. Exposure of pulmonary endothelial cells to RBC-derived microparticles promotes an inflammatory response, but the mechanisms underlying microparticle-induced endothelial cell activation are poorly understood. In the present study, cultured murine lung endothelial cells (MLECs) were treated with microparticles isolated from aged murine packed RBCs or vehicle. Microparticle-treated cells demonstrated increased expression of the adhesion molecules ICAM and E-selectin, as well as the cytokine, IL-6. To identify mechanisms that mediate these effects of microparticles on MLECs, cells were treated with microparticles covalently bound to carboxyfluorescein succinimidyl ester (CFSE) and cellular uptake of microparticles was quantified via flow cytometry. Compared with controls, there was a greater proportion of CFSE-positive MLECs from 15 min up to 24 h, suggesting endocytosis of the microparticles by endothelial cells. Colocalization of microparticles with lysosomes was observed via immunofluorescence, indicating endocytosis and endolysosomal trafficking. This process was inhibited by endocytosis inhibitors. SiRNA knockdown of Rab5 signaling protein in endothelial cells resulted in impaired microparticle uptake as compared with nonsense siRNA-treated cells, as well as an attenuation of the inflammatory response to microparticle treatment. Taken together, these data suggest that endocytosis of RBC-derived microparticles by lung endothelial cells results in endothelial cell activation. This response seems to be mediated, in part, by the Rab5 signaling protein.
Paediatric traumatic brain injury: prognostic insights and outlooks
Authors: Au Alicia K. , Clark Robert S.B.
Published: September 2017

Purpose of review

Traumatic brain injury (TBI) is a leading cause of death and disability in children. Prognostication of outcome following TBI is challenging in this population and likely requires complex, multimodal models to achieve clinically relevant accuracy. This review highlights injury characteristics, physiological indicators, biomarkers and neuromonitoring modalities predictive of outcome that may be integrated for future development of sensitive and specific prognostic models.

Recent findings

Paediatric TBI is responsible for physical, psychosocial and neurocognitive deficits that may significantly impact quality of life. Outcome prognostication can be difficult in the immature brain, but is aided by the identification of novel biomarkers (neuronal, astroglial, myelin, inflammatory, apoptotic and autophagic) and neuromonitoring techniques (electroencephalogram and MRI). Investigation in the future may focus on assessing the prognostic ability of combinations of biochemical, protein, neuroimaging and functional biomarkers and the use of mathematical models to develop multivariable predication tools to improve the prognostic ability following childhood TBI.

Prognostication of outcome following paediatric TBI is multidimensional, influenced by injury severity, age, physiological factors, biomarkers, electroencephalogram and neuroimaging. Further development, integration and validation of combinatorial prognostic algorithms are necessary to improve the accuracy and timeliness of prognosis in a meaningful fashion.
LDJump: Estimating Variable Recombination Rates from Population Genetic Data
Authors: Hermann Philipp , Heissl Angelika , Tiemann-Boege Irene , Futschik Andreas
Published: September 2017

As recombination plays an important role in evolution, its estimation, as well as, the identification of hotspot positions is of considerable interest. We propose a novel approach for estimating historical recombination along a chromosome that involves a sequential multiscale change point estimator. Our method also permits to take demography into account. It uses a composite likelihood estimate and other summary statistics within a regression model fitted on suitable scenarios. Our proposed method is accurate, computationally fast, and provides a parsimonious solution by ensuring a type I error control against too many changes in the recombination rate. An application to human genome data suggests a good congruence between our estimated and experimentally identified hotspots. Our method is implemented in theR-packageLDJump, which is freely available fromhttps://github.com/PhHermann/LDJump.
Memory entrainment by visually evoked theta-gamma coupling
Authors: Köster Moritz , Martens Ulla , Gruber Thomas
Published: September 2017

It is an integral function of the human brain to sample novel information from the environment and to update the internal representation of the external world. The formation of new memories is assumed to be orchestrated by neuronal oscillations, the rhythmic synchronization of neuronal activity within and across cell assemblies. Specifically, successful encoding of novel information is associated with increased theta oscillations (3-8Hz) and theta coupled gamma activity (40-120Hz), and a decrease in alpha oscillations (8-12Hz). However, given the correlative nature of neurophysiological recordings, the causal role of neuronal rhythms in human memory encoding is still unclear. Here, we experimentally enhance the formation of novel memories by a visual brain stimulation at an individually adjusted theta frequency, in contrast to the stimulation at an individual alpha frequency. Critically, the memory entrainment effect by the theta stimulation was not explained by theta powerper se, but was driven by visually evoked theta-gamma coupling in wide spread cortical networks. These findings provide first evidence for a functional role of the theta rhythm and the theta-gamma neuronal code in human episodic memory. Yet more strikingly, the entrainment of mnemonic network mechanisms by a simplistic visual stimulation technique provides a proof of concept that internal rhythms align with visual pacemakers, which can entrain complex cognitive functions in the wake human brain.
Targeting temporal dynamics of microenvironmental factors halts tumor migration and alleviates effects of dynamic tumor heterogeneity
Authors: Singh Manjulata , Tian Xiao-Jun , Donnenberg Vera S. , Watson Alan M , Zhang Jingyu , Stabile Laura P. , Watkins Simon C. , Xing Jianhua , Sant Shilpa
Published: September 2017

Targeting microenvironmental factors that foster migratory cell phenotypes is a promising strategy for halting tumor migration. However, lack of mechanistic understanding of the process impedes pharmaceutical drug development. Using a novel 3D microtumor model with tight control over tumor size, we recapitulated tumor size-induced hypoxic microenvironment and emergence of migratory phenotypes in epithelial T47D breast microtumors as well as those of patient-derived primary metastatic breast cancer cells, mesothelioma cells and lung cancer xenograft cells (PDX). The microtumor models from various patient-derived tumor cells and PDX cells revealed upregulation of tumor secretome, matrix metalloproteinase-9 (MMP9), fibronectin (FN), and soluble E-cadherin (sE-CAD) consistent with the clinically reported elevated levels of FN and MMP9 in the patient breast tumors compared to healthy mammary gland. We further showed that the tumor secretome induces migratory phenotype in non-hypoxic, non-migratory small microtumors. Subsequent mathematical model analysis identified a two-stage microtumor progression and migration mechanism, i.e., hypoxia induces migratory phenotype in the early initialization stage, which then becomes self-sustained through positive feedback loop established among the secretome. Both computational and experimental studies showed that inhibition of tumor secretome effectively halts microtumor migration despite tumor heterogeneity, while inhibition of the hypoxia is effective only within a time window and is compromised by tumor-to-tumor variation of the growth dynamics, supporting our notion that hypoxia initiates migratory phenotypes but does not sustain it. In summary, we show that targeting temporal dynamics of evolving microenvironments during tumor progression can halt and bypass major hurdle of tumor heterogeneity.
Non-canonical circadian oscillations inDrosophilaS2 cells drive gene-expression cycles coupled to metabolic oscillations
Authors: Rey Guillaume , Milev Nikolay B. , Valekunja Utham K. , Ch Ratnasekhar , Ray Sandipan , Dos Santos Mariana Silva , Nagy Andras D. , Antrobus Robin , MacRae James I. , Reddy Akhilesh B.
Published: September 2017

Circadian rhythms are cell-autonomous biological oscillations with a period of about 24 hours. Current models propose that transcriptional feedback loops are the principal mechanism for the generation of circadian oscillations. In these models,DrosophilaS2 cells are generally regarded as ‘non-rhythmic’ cells, as they do not express several canonical circadian components. Using an unbiased multi-omics approach, we made the surprising discovery thatDrosophilaS2 cells do in fact display widespread daily rhythms. Transcriptomics and proteomics analyses revealed that hundreds of genes and their products are rhythmically expressed in a 24-hour cycle. Metabolomics analyses extended these findings and illustrated that central carbon metabolism and amino acid metabolism are the main pathways regulated in a rhythmic fashion. We thus demonstrate that daily genome-wide oscillations, coupled to metabolic cycles, take place in eukaryotic cells without the contribution of known circadian regulators.
Urinary candidate biomarkers in an experimental autoimmune myocarditis rat model
Authors: Zhao Mindi , Wu Jiangqiang , Li Xundou , Gao Youhe
Published: September 2017

Urine is a better source than plasma for biomarker studies, as it can accumulate all changes in the body. Various candidate urinary biomarkers of physiological conditions, kidney disease and even brain dysfunction, have been detected in urine; however, urine has rarely been used to reflect cardiac diseases. As the clinical presentations of myocarditis are heterogeneous, reliable and sensitive diagnostic biomarkers of myocarditis are very important. In this study, candidate urinary biomarkers in the myosin-induced autoimmune myocarditis rat models were characterized using the isobaric tandem mass tag labeling approach coupled with high-resolution mass spectrometry. Compared with controls, forty-six urinary proteins were significantly changed in the myocarditis rats; among them, ten had previously been associated with myocarditis, twelve corresponding gene products have been annotated as mainly cardiovascular network genes by the Ingenuity Pathway Analysis, and four urinary proteins were validated by western blot.
Binding language: Structuring sentences through precisely timed oscillatory mechanisms
Authors: Segaert Katrien , Mazaheri Ali , Hagoort Peter
Published: September 2017

Syntactic binding refers to combining words into larger structures. Using EEG, we investigated the neural processes involved in syntactic binding. Participants were auditorily presented two-word sentences (i.e. a pronoun and pseudoverb such as ‘she dotches’, for which syntactic binding can take place) and wordlists (i.e. two pseudoverbs such as ‘pob dotches’, for which no binding can occur). Comparing these two conditions, we targeted syntactic binding while minimizing contributions of semantic binding and of other cognitive processes such as working memory. We found a converging pattern of results using two distinct analysis approaches: one approach using frequency bands as defined in previous literature, and one data-driven approach in which we looked at the entire range of frequencies between 3-30 Hz without the constraints of pre-defined frequency bands. In the syntactic binding (relative to the wordlist) condition, a power increase was observed in the alpha and beta frequency range shortly preceding the presentation of the target word that requires binding, which was maximal over frontal-central electrodes. Our interpretation is that these signatures reflect that language comprehenders expect the need for binding to occur. Following the presentation of the target word in a syntactic binding context (relative to the wordlist condition), an increase in alpha power maximal over a left lateralized cluster of frontal-temporal electrodes was observed. We suggest that this alpha increase relates to syntactic binding taking place. Taken together, our findings suggest that increases in alpha and beta power are reflections of distinct the neural processes underlying syntactic binding.
Whole-Brain Vasculature Reconstruction at the Single Capillary Level
Authors: Di Giovanna Antonino Paolo , Tibo Alessandro , Silvestri Ludovico , Müllenbroich Marie Caroline , Costantini Irene , Allegra Mascaro Anna Letizia , Sacconi Leonardo , Frasconi Paolo , Pavone Francesco Saverio
Published: September 2017

The distinct organization of the brain’s vascular network ensures that it is adequately supplied with oxygen and nutrients. However, despite this fundamental role, a detailed reconstruction of the brain-wide vasculature at the capillary level remains elusive, due to insufficient image quality using the best available techniques. Here, we demonstrate a novel approach that improves vascular demarcation by combining CLARITY with a vascular staining approach that can fill the entire blood vessel lumen and imaging with light-sheet fluorescence microscopy. This method significantly improves image contrast, particularly in depth, thereby allowing reliable application of automatic segmentation algorithms, which play an increasingly important role in high-throughput imaging of the terabyte-sized datasets now routinely produced. Furthermore, our novel method is compatible with endogenous fluorescence, thus allowing simultaneous investigations of vasculature and genetically targeted neurons. We believe our new method will be valuable for future brain-wide investigations of the capillary network.
Evaluating the Role of Cell-free Fetal DNA in Inflammation and Spontaneous Preterm Birth
Authors: van Boeckel Sara R , MacPherson Heather , Davidson Donald J , Norman Jane E , Stock Sarah J
Published: September 2017

Preterm birth is the leading cause of neonatal mortality. While spontaneous preterm birth (sPTB) is the cause of over 70% of PTB, the pathogenesis behind sPTB remains unclear. Cell-free fetal DNA (cff-DNA) originates from the placenta and is increased in women who develop PTB. It has been demonstrated that fetal DNA is hypomethylated and is pro-inflammatory. The pro-inflammatory properties of placental-derived DNA, the effects of placental inflammation on the production of cff-DNA, and its significance in the pathogenesis of PTB are unknown.

Using a human placental explant model, we analysed the effect of lipopolysaccharide (LPS) stimulation on cff-DNA production, and used the cff-DNA generated by these explants to examine the methylation profile andin-vitropro-inflammatory properties of cff-DNA. LPS caused significant production of TNF-α from placental explants, but did not significantly increase the cff-DNA production. Placental-derived cff-DNA, was found to have a small proportion of unmethylated CpG motifs, but was more similar to adult DNA than to more highly unmethylated E-coli DNA. However, cff-DNA did not elicit production of inflammatory cytokines (IL-6, IL-8, TNF-α and CXCL10) by peripheral blood mononuclear cells from pregnant women. Furthermore, in contrast to LPS, intra-uterine injections of mouse placental DNA did not decrease time to delivery in anin-vivomouse PTB model compared to control animals.

This study demonstrates that placental inflammation does not increase the production of cff-DNA in placental explants, and cff-DNA alone is not sufficient to elicit an inflammatory response in human PBMC culturesex-vivo.It also shows that mouse placental DNA does not cause PTBin-vivo.This suggests that cff-DNA might be predominantly an effect of parturition and not a principal causative agent.
Sweeping genomic remodeling through repeated selection of alternatively adapted haplotypes occurs in the first decades after marine stickleback colonize new freshwater ponds
Authors: Bassham Susan , Catchen Julian , Lescak Emily , von Hippel Frank A. , Cresko William A.
Published: September 2017

Heterogeneous genetic divergence can accumulate across the genome when populations adapt to different habitats while still exchanging alleles. How long does diversification take and how much of the genome is affected? When divergence occurs in parallel from standing genetic variation, how often are the same haplotypes used? We explore these questions using RAD-seq genotyping data, and show that broad-scale genomic re-patterning, fueled by standing variation, can emerge in just dozens of generations in replicate natural populations of threespine stickleback fish (Gasterosteus aculeatus). After the catastrophic 1964 Alaskan earthquake, marine stickleback colonized newly created ponds on seismically uplifted islands. We find that freshwater fish in these young ponds differ from their marine ancestors across the same genomic segments previously shown to have diverged in much older lake populations. Outside of these core divergent regions the genome shows no population structure across the ocean-freshwater divide, consistent with strong local selection acting in alternative environments on stickleback populations still connected by significant gene flow.Reinforcing this inference, a majority of divergent haplotypes that are at high frequency in ponds are shared across independent freshwater populations and are detectable, at low frequency, in the sea even across great geographic distances. Building upon previous work in this model species for population genomics, our data suggest that a long history of divergent selection and gene flow across stickleback in oceanic and freshwater habitats has created balanced polymorphism in large genomic blocks of alternatively adapted DNA sequences, ultimately stoking - and potentially channeling - rapid, parallel evolution.
Winter warming effects on tundra shrub performance are species‐specific and dependent on spring conditions
Authors: Krab Eveline J. , Roennefarth Jonas , Becher Marina , Blume‐Werry Gesche , Keuper Frida , Klaminder Jonatan , Kreyling Juergen , Makoto Kobayashi , Milbau Ann , Dorrepaal Ellen
Published: September 2017

Climate change‐driven increases in winter temperatures positively affect conditions for shrub growth in arctic tundra by decreasing plant frost damage and stimulation of nutrient availability. However, the extent to which shrubs may benefit from these conditions may be strongly dependent on the following spring climate. Species‐specific differences in phenology and spring frost sensitivity likely affect shrub growth responses to warming. Additionally, effects of changes in winter and spring climate may differ over small spatial scales, as shrub growth may be dependent on natural variation in snow cover, shrub density and cryoturbation.

We investigated the effects of winter warming and altered spring climate on growing‐season performance of three common and widespread shrub species in cryoturbated non‐sorted circle arctic tundra. By insulating sparsely vegetated non‐sorted circles and parts of the surrounding heath with additional snow or gardening fleeces, we created two climate change scenarios: snow addition increased soil temperatures in autumn and winter and delayed snowmelt timing without increasing spring temperatures, whereas fleeces increased soil temperature similarly in autumn and winter, but created warmer spring conditions without altering snowmelt timing.

Winter warming affected shrub performance, but the direction and magnitude were species‐specific and dependent on spring conditions. Spring warming advanced, and later snowmelt delayed canopy green‐up. The fleece treatment did not affect shoot growth and biomass in any shrub species despite decreasing leaf frost damage in Empetrum nigrum. Snow addition decreased frost damage and stimulated growth of Vaccinium vitis‐idaea by c. 50%, while decreasing Betula nana growth (p < .1). All of these effects were consistent the mostly barren circles and surrounding heath.

Synthesis. In cryoturbated arctic tundra, growth of Vaccinium vitis‐idaea may substantially increase when a thicker snow cover delays snowmelt, whereas in longer term, warmer winters and springs may favour E. nigrum instead. This may affect shrub community composition and cover, with potentially far‐reaching effects on arctic ecosystem functioning via its effects on cryoturbation, carbon cycling and trophic cascading. Our results highlight the importance of disentangling effects of winter and spring climate change timing and nature, as spring conditions are a crucial factor in determining the impact of winter warming on plant performance.
The Financialization of Housing Production in Brussels
Authors: Romainville Alice
Published: September 2017

This article focuses on the financialization of housing production in the Brussels‐Capital Region, examining the increased presence and use of financial capital in housing production. Information collected by local administrations when granting building permits is used to undertake a large‐scale examination of companies involved in housing provision in Brussels in the 2000s in order to identify the origins of capital invested in housing development projects and to assess to what extent it can be considered as ‘financialized’. The use of this data set allows me to estimate the ‘market share’ of financial capital in housing production and to analyse the geography of these investments in the built environment. This spatial analysis also provides some insights for a discussion about the possible social consequences of this influx of financial capital into the urban space. The task of empirically ‘measuring’ financialization raises numerous methodological questions. A choice has to be made between a wide range of definitions, both for financial activities and the financialization process. Moreover, for the purpose of quantifying the phenomenon, these concepts are made operational and turned into indicators. In addition to providing information about the investment of financial capital in housing production and the concrete forms it may take in a city such as Brussels, I venture to suggest that this article also contributes to the methodological ‘toolbox’ available to researchers in the field of financialization.
Textural and microstructural properties of Kradi cheese (an indigenous cheese of Jammu and Kashmir, India)
Authors: Punoo Hilal Ahmad , Patil Girdhari ramdas , Bijoy Ram Ran
Published: September 2017

The texture and microstructure of Kradi cheese, an indigenous fresh unripened cheese of Jammu and Kashmir, India, were studied. There were significant differences (P < 0.05) for hardness, adhesiveness, springiness, cohesiveness, chewiness and resilience between samples from four different market areas. The optimised products made in the laboratory from cultures NCDC‐167 and NCDC‐144 showed significant differences (P < 0.05) in the textural and mechanical properties of tensile strength. The microstructure of the market samples was distinguished by the greater size of the voids present in three‐dimensional casein network. The optimised laboratory product had a more compact and fibrous structure compared to the market samples, which was attributed to its higher protein content.
The Corticotropin Releasing Factor Receptor 1 in Alcohol Use Disorder: Still a Valid Drug Target?
Authors: Pomrenze Matthew B. , Fetterly Tracy L. , Winder Danny G. , Messing Robert O.
Published: September 2017

Corticotropin releasing factor (CRF) is a neuropeptide that plays a key role in behavioral and physiological responses to stress. A large body of animal literature implicates CRF acting at type 1 CRF receptors (CRFR1) in consumption by alcohol‐dependent subjects, stress‐induced reinstatement of alcohol seeking, and possibly binge alcohol consumption. These studies have encouraged recent pilot studies of CRFR1 antagonists in humans with alcohol use disorder (AUD). It was a great disappointment to many in the field that these studies failed to show an effect of these compounds on stress‐induced alcohol craving. Here, we examine these studies to explore potential limitations and discuss preclinical and human literature to ask whether CRFR1 is still a valid drug target to pursue for the treatment of AUD.
Alcohol‐Induced Behaviors Require a Subset of Drosophila JmjC‐Domain Histone Demethylases in the Nervous System
Authors: Pinzón Jorge H. , Reed Addison R. , Shalaby Nevine A. , Buszczak Michael , Rodan Aylin R. , Rothenfluh Adrian
Published: September 2017

Background

Long‐lasting transcriptional changes underlie a number of adaptations that contribute to alcohol use disorders (AUD). Chromatin remodeling, including histone methylation, can confer distinct, long‐lasting transcriptional changes, and histone methylases are known to play a role in the development of addiction. Conversely, little is known about the relevance of Jumonji (JmjC) domain‐containing demethylases in AUDs. We systematically surveyed the alcohol‐induced phenotypes of null mutations in all 13 Drosophila JmjC genes.

Methods

We used a collection of JmjC mutants, the majority of which we generated by homologous recombination, and assayed them in the Booze‐o‐mat to determine their naïve sensitivity to sedation and their tolerance (change in sensitivity upon repeat exposure). Mutants with reproducible phenotypes had their phenotypes rescued with tagged genomic transgenes, and/or phenocopied by nervous system‐specific knockdown using RNA interference (RNAi).

Results

Four of the 13 JmjC genes (KDM3, lid, NO66, and HSPBAP1) showed reproducible ethanol (EtOH) sensitivity phenotypes. Some of the phenotypes were observed across doses, for example, the enhanced EtOH sensitivity of KDM3KO and NO66KO, but others were dose dependent, such as the reduced EtOH sensitivity of HSPBAP1KO, or the enhanced EtOH tolerance of NO66KO. These phenotypes were rescued by their respective genomic transgenes in KDM3KO and NO66KO mutants. While we were unable to rescue lidk mutants, knockdown of lid in the nervous system recapitulated the lidk phenotype, as was observed for KDM3KO and NO66KO RNAi‐mediated knockdown.

Conclusions

Our study reveals that the Drosophila JmjC‐domain histone demethylases Lid, KDM3, NO66, and HSPBAP1 are required for normal EtOH‐induced sedation and tolerance. Three of 3 tested of those 4 JmjC genes are required in the nervous system for normal alcohol‐induced behavioral responses, suggesting that this gene family is an intriguing avenue for future research.
The haemostatic efficacy and foreign body reaction of epinephrine–Impregnated polyurethane foam in osseous defects
Authors: Torabinejad Mahmoud , Kang Hyun J. S. , Maskiewicz Richard , Grandhi Anupama
Published: September 2017

The objective of this study was to compare the haemostatic efficacy and foreign body reaction of epinephrine–impregnated cotton pellets with those of epinephrine‐impregnated polyurethane (PU) foam cubes in osseous defects created in guinea pigs. Initially, these substances were randomly applied to the osseous defects in guinea pigs for 2 min and blood loss was measured. The animals were then sacrificed 7 weeks later and the degree of foreign body reaction was scored. The data were analysed by the independent‐samples Kruskal‐Wallis test. Epinephrine‐impregnated PU foam cubes showed significantly better haemostatic effect compared to epinephrine–impregnated cotton pellets. The PU foam containing epinephrine specimens elicited significantly less foreign body reaction compared to epinephrine cotton pellets (P < 0.05). Based on the results of this study, it is concluded that epinephrine‐impregnated PU foam cubes are a good alternative to epinephrine‐impregnated cotton pellets as a local haemostatic agent in endodontic surgery.
The structural transformation of African agriculture and rural spaces: introduction to a special section†
Authors: Barrett Christopher B. , Christian Paul , Shiferaw Bekele A.
Published: September 2017

This article briefly introduces a special section on the structural transformation of African agriculture and rural spaces. The five papers that comprise this special section all draw on household‐level microdata to explore important aspects of the salient changes taking place in the world's most agrarian and poorest continent.
The fourth industrial revolution, agricultural and rural innovation, and implications for public policy and investments: a case of India
Authors: Lele Uma , Goswami Sambuddha
Published: September 2017

The Indian Government and public–private partnerships are developing and disseminating a dizzying number of innovative, networked solutions, broadly known as the Digital India initiative, to increase the efficiency of safety nets and worker productivity and to improve life. Yet, challenges to turn the power of information and other technologies into a farmer‐friendly technological revolution for India's 156 million rural households are considerable, including: (1) reliable, up‐to‐date, location‐specific message content for a diverse agriculture to help stratified households shift to productive, knowledge‐intensive agriculture as a business—government, private sector, and civil society have big roles to play; (2) digital literacy, i.e., teaching farmers how to choose and use apps, even where the digital divide is absent; apps are, or soon to be, in regional languages; and (3) monitoring actual use and impacts on users’ lives by understanding the adoption and adaptation processes. These challenges call for bottom‐up, complementary investments in physical, human, and institutional capital, and farmer‐friendly e‐platforms, while forging ahead with many top‐down policy and institutional reforms currently underway, in which progress is real and constraints holding back greater success are better understood.
Information sharing as a safeguard against the opportunistic behavior of South African Karoo Lamb farmers
Authors: van der Merwe Melissa , Kirsten Johann F. , Trienekens Jacques H.
Published: September 2017

Misconduct in global meat supply chains are omnipresent and even more so in differentiated chains where credence attributes such as origin and taste are used to differentiate the product. By definition, these attributes signal asymmetric information which implies that in the presence of bounded rational individuals with conflicting interests, misconduct in the form of opportunistic behavior is bound to prevail. Increased information exchange through farmer networks is, however, expected to reduce opportunistic behavior. In the case of a differentiated meat product, such as Karoo Lamb, the article studies the farmer‐abattoir transaction with the purpose of recommending strategies that can be implemented to reduce the farmer's tendency to behave opportunistically. The article employs the PLS approach to SEM and reveals a significant negative relationship between information shared and opportunistic behavior. The results indicate significant positive relationships between trust in the abattoir and information shared as well as between farmer networks and information shared. These results are indicative of the support provided to the information shared construct by higher levels of trust between farmers and abattoirs and established farmer networks. It is, therefore, recommended that differentiated meat supply chains, through their various associations, concentrate their efforts to promote information sharing by building stronger, trust centered relationships and by supporting farmer networks.
The Internet Game Use‐Elicited Symptom Screen proved to be a valid tool for adolescents aged 10–19 years
Authors: Jo Sun‐Jin , Yim Hyeon Woo , Lee Hae‐Kook , Lee Hyung Cho , Choi Jung‐Seok , Baek Kyung‐Young
Published: September 2017

Aim

This study tested the diagnostic validity of the nine‐item Internet Game Use‐Elicited Symptom Screen (IGUESS) tool, which was developed by the authors after the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, identified Internet gaming as a condition that needed further study.

Methods

A self‐report screening test comprising IGUESS and Young's Internet Addiction Test was administered to 121 adolescents (74% boys) with a median age of 14 (range 10–19) recruited from school and health settings in Korea. After the screening test, a clinician conducted one‐to‐one interviews with all of the subjects to set a gold standard for diagnosis.

Results

The sensitivity and specificity of IGUESS were 87.0 and 86.7%, respectively, for a cut‐off score of 10 points, with an area under the curve value of 0.93. Its reliability, as determined by Cronbach's alpha, was 0.94, and the correlation coefficient between IGUESS and Young's Internet Addiction Test was r = 0.902.

Conclusion

The findings suggest that a cut‐off score of 10 is appropriate for administering the IGUESS in various community‐based settings, including schools, to screen for potential subjects in need of further assessment for Internet gaming problems.
Statins reduce the risk of liver decompensation and death in chronic viral hepatitis: a propensity score weighted landmark analysis
Authors: Wong J. C.‐T. , Chan H. L.‐Y. , Tse Y.‐K. , Yip T. C.‐F. , Wong V. W.‐S. , Wong G. L.‐H.
Published: September 2017

Background

Decompensated liver disease due to portal hypertension leads to significant morbidity and mortality. Statins can modulate intrahepatic vascular tone, but the clinical significance remains uncertain.

Aim

To determine the effects of statin use on the risk of liver decompensation and death among patients with chronic viral hepatitis.

Methods

We conducted a population wide cohort study using a hospital based database from the Hong Kong Hospital Authority. Adults with chronic viral hepatitis without prior liver decompensation were identified from 2000 to 2012 by International Classification of Diseases, Ninth Revision, Clinical Modification, diagnostic codes. Statin use was defined as a cumulative defined daily dose of >28. Landmark analysis was used to overcome immortal time bias. Propensity score weighting was further performed to minimise baseline confounders. Primary outcome was a composite of portal hypertension related liver decompensation events, with adjustment for death as a competing risk.

Results

A total of 69 184 patients with chronic viral hepatitis (2053 statin users and 67 131 statin non‐users) were identified for the 2‐year landmark analysis. After propensity score weighting of 23 baseline covariates, statin use was associated with a significant reduction in composite liver decompensation events (HR: 0.55; 95% CI: 0.36‐0.83; P = .005), ascites (HR: 0.57; 95% CI: 0.36‐0.92; P = .02), and a dose‐dependent decrease in death (HR: 0.87; 95% CI: 0.76‐0.99; P = .035) relative to no statin use.

Conclusions

Patients with chronic viral hepatitis who used statins have a reduced risk of liver decompensation and death compared to non‐users in this propensity score weighted landmark analysis.
The impact of the hope growing account program on participants’ economic well‐being in South Korea
Authors: Weon Soyoon , Rothwell David W.
Published: September 2017

In 2010, the Korean government introduced the Hope Growing Account (Hope) program. The Hope program combines elements of a social assistance scheme (monthly income grants) with matched funds for savings to encourage the working poor to increase income and build assets. This longitudinal study estimated changes in household economic well‐being among 895 low‐income households who participated in Hope between 2010 and 2012. Economic well‐being was measured by changes in household monthly income and income‐to‐needs ratio. The adjusted difference‐in‐differences estimation revealed that the impact of Hope varied over household income distributions: lower income households were more likely to increase their monthly earned income and income‐to‐needs ratio compared to demographically similar non‐participants, while higher income households were less likely to increase their income and income‐to‐needs ratio. We describe how future research is needed to better understand how the Hope program impacts household assets and behavioral changes in the long run.
G protein‐coupled receptors not currently in the spotlight: free fatty acid receptor 2 and GPR35
Authors: Milligan Graeme
Published: September 2017

It is widely appreciated that G protein‐coupled receptors have been the most successfully exploited class of targets for the development of small molecule medicines. Despite this, to date, less than 15% of the non‐olfactory G protein‐coupled receptors in the human genome are the targets of a clinically used medicine. In many cases, this is likely to reflect a lack of understanding of the basic underpinning biology of many G protein‐coupled receptors that are not currently in the spotlight, as well as a paucity of pharmacological tool compounds and appropriate animal models to test in vivo function of such G protein‐coupled receptors in both normal physiology and in the context of disease. ‘Open Innovation’ arrangements, in which pharmaceutical companies and public–private partnerships provide wider access to tool compounds identified from ligand screening programmes, alongside enhanced medicinal chemistry support to convert such screening ‘hits’ into useful ‘tool’ compounds will provide important routes to improved understanding. However, in parallel, novel approaches to define and fully appreciate the selectivity and mode of action of such tool compounds, as well as better understanding of potential species orthologue variability in the pharmacology and/or signalling profile of a wide range of currently poorly understood and understudied G protein‐coupled receptors, will be vital to fully exploit the therapeutic potential of this large target class. I consider these themes using as exemplars two G protein‐coupled receptors, free fatty acid receptor 2 and GPR35.
Potential biological targets for bioassay development in drug discovery of Sturge–Weber syndrome
Authors: Mohammadipanah Fatemeh , Salimi Fatemeh
Published: September 2017

Sturge–Weber Syndrome (SWS) is a neurocutaneous disease with clinical manifestations including ocular (glaucoma), cutaneous (port‐wine birthmark), neurologic (seizures), and vascular problems. Molecular mechanisms of SWS pathogenesis are initiated by the somatic mutation inGNAQ. Therefore, no definite treatments exist for SWS and treatment options only mitigate the intensity of its clinical manifestations. Biological assay design for drug discovery against this syndrome demands comprehensive knowledge on mechanisms which are involved in its pathogenesis. By analysis of the interrelated molecular targets of SWS, some in vitro bioassay systems can be allotted for drug screening against its progression. Development of such platforms of bioassay can bring along the implementation of high‐throughput screening of natural or synthetic compounds in drug discovery programs. Regarding the fact that study of molecular targets and their integration in biological assay design can facilitate the process of effective drug discovery; some potential biological targets and their respective biological assay for SWS drug discovery are propounded in this review. For this purpose, some biological targets for SWS drug discovery such as acetylcholinesterase, alkaline phosphatase, GABAergic receptors, Hypoxia‐Inducible Factor (HIF)‐1α and 2α are suggested.
Bystander Responses to Bias‐Based Bullying in Schools: A Developmental Intergroup Approach
Authors: Palmer Sally B. , Abbott Nicola
Published: September 2017

Research on bystanders' responses to bullying shows the valuable contribution that prosocial or defender behaviors can have in reducing bullying in schools. In this article, we propose that a developmental intergroup approach (i.e., a developing understanding of social identities and related intergroup processes) is required to understand fully when and why children and adolescents help bullied peers in diverse contexts. First, we review theory and evidence on intergroup social exclusion to demonstrate the strength of a developmental intergroup approach when understanding responses to complex social scenarios in childhood and adolescence. Then, we review recent evidence that demonstrates the importance of examining group membership, group identity, and group norms to understand children's and adolescents' responses as bystanders in the context of bias‐based bullying. Finally, we consider implications for school‐based interventions and next steps for research.
A Conceptual Framework for Detecting Cheating in Online and Take‐Home Exams
Authors: D'Souza Kelwyn A. , Siegfeldt Denise V.
Published: September 2017

Selecting the right methodology to use for detecting cheating in online exams requires considerable time and effort due to a wide variety of scholarly publications on academic dishonesty in online education. This article offers a cheating detection framework that can serve as a guideline for conducting cheating studies. The necessary theories and related statistical models are arranged into three phases/sections within the framework to allow cheating studies to be completed in a sufficiently quick and precise manner. This cheating detection framework includes commonly used models in each phase and addresses the collection and analysis of the needed data. The model's level of complexity ascends progressively from a graphical representation of data and descriptive statistical models to more advanced inferential statistics, correlation analysis, regression analysis, and the optional comparison method and the Goldfeld‐Quandt Test for heteroskedasticity. An instructor receiving positive results on the possibility of cheating in Phases 1 or 2 can avoid using more advanced models in Phase 3. Tests conducted on sample courses showed that models in Phases 1 and 2 of the proposed framework provided results effectively for over 70% of the test groups, saving users further time and effort. High‐tech systems and low‐cost recommendations that can mitigate cheating are discussed. This framework will be beneficial in guiding instructors who are converting from the traditionally proctored in‐class exam to a take‐home or online exam without authentication or proctoring. In addition, it can serve as a powerful deterrent that will alleviate the concerns that an institution's stakeholders might have about the reliability of their programs.
Export and Innovation in Small and Medium Enterprises: The Role of Concentrated Bank Borrowing
Authors: Mancusi Maria Luisa , Vezzulli Andrea , Frazzoni Serena , Rotondi Zeno , Sobrero Maurizio
Published: September 2017

This paper assesses the role of concentrated bank borrowing in explaining the extensive and intensive margins of export, while accounting for the simultaneous relationship between exporting and innovation. Concentrated bank borrowing proxies for the intensity of the bank–firm relationship and is a strategy often pursued by small and medium enterprises (SMEs) in order to overcome information asymmetries and improve access to external finance. Our results show that a tight relationship between an SME and its main bank increases both the firm's probability of exporting and its export intensity. This positive effect is only marginally mediated by the SME's increased propensity to introduce product innovation. We further discuss the financial and non‐financial channels through which the intensity of the bank–firm relationship supports SMEs’ international activities.
The ‘Hutchinsonian niche’ as an assemblage of demographic niches: implications for species geographic ranges
Authors: Pironon Samuel , Villellas Jesús , Thuiller Wilfried , Eckhart Vincent M. , Geber Monica A. , Moeller David A. , García María B.
Published: September 2017

Hutchinson defined the ecological niche as a hypervolume shaped by the environmental conditions under which a species can ‘exist indefinitely’. Although several authors further discussed the need to adopt a demographic perspective of the ecological niche theory, very few have investigated the environmental requirements of different components of species’ life cycles (i.e. vital rates) in order to examine their internal niche structures. It therefore remains unclear how species’ demography, niches and distributions are interrelated. Using comprehensive demographic data for two well‐studied, short‐lived plants (Plantago coronopus, Clarkia xantiana), we show that the arrangement of species’ demographic niches reveals key features of their environmental niches and geographic distributions. In Plantago coronopus, opposing geographic trends in some individual vital rates, through different responses to environmental gradients (demographic compensation), stabilize population growth across the range. In Clarkia xantiana, a lack of demographic compensation underlies a gradient in population growth, which could translate in a directional geographic range shift. Overall, our results highlight that occurrence and performance niches cannot be assumed to be the same, and that studying their relationship is essential for a better understanding of species’ ecological niches. Finally, we argue for the value of considering the assemblage of species’ demographic niches when studying ecological systems, and predicting the dynamics of species geographical ranges.
A Modified DBSCAN Clustering Method to Estimate Retail Center Extent
Authors: Pavlis Michalis , Dolega Les , Singleton Alex
Published: September 2017

This research introduces a new method for the identification of local retail agglomerations within Great Britain, implementing a modification of the established density based spatial clustering of applications with noise (DBSCAN) method that improves local sensitivity to variable point densities. The variability of retail unit density can be related to both the type and function of retail centers, but also to characteristics such as size and extent of urban areas, population distribution, or property values. The suggested method implements a sparse graph representation of the retail unit locations based on a distance‐constrained k‐nearest neighbor adjacency list that is subsequently decomposed using the Depth First Search algorithm. DBSCAN is iteratively applied to each subgraph to extract the clusters with point density closer to an overall density for each study area. This innovative approach has the advantage of adjusting the radius parameter of DBSCAN at the local scale, thus improving the clustering output. A comparison of the estimated retail clusters against a sample of existing boundaries of retail areas shows that the suggested methodology provides a simple yet accurate and flexible way to automate the process of identifying retail clusters of varying shapes and densities across large areas; and by extension, enables their automated update over time.