bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromatin architecture reorganisation during neuronal cell differentiation in Drosophila genome
Authors: Chathoth Keerthi T , Zabet Nicolae Radu
Published: August 2018

Compartmentalisation of the genome as topologically associating domains (TADs) may have regulatory role in development and cellular functioning, but the, mechanism involved in TAD establishment is still unclear. Here, we present the first high-resolution contact map ofDrosophila melanogasterneuronal cells (BG3) and identified different classes of TADs by comparing this to genome organisation in embryonic cells (Kc167). We find new rearrangements during differentiation in neuronal cells reflected as enhanced long-range interactions, which is supported by pronounced enrichment of CTCF at cell type specific borders. Furthermore, we show the presence of strong divergent transcription corroborated with RNA Polymerase II occupancy and increased DNA accessibility at the TAD borders. Interestingly, TAD borders that are specific to neuronal cells are enriched in enhancers controlled by neuronal specific transcription factors. Our results suggest that TADs are dynamic across developmental stages and reflect the interplay between insulators, transcriptional states and enhancer activities.
Catalytic promiscuity potentiated the divergence of new cytochrome P450 enzyme functions in cyanogenic defense metabolism
Authors: Barco Brenden , Zipperer Lara , Clay Nicole K.
Published: August 2018

Cytochrome P450 monooxygenases (P450s) constitute the largest metabolic enzyme family in plants, responsible for synthesizing hundreds of thousands of specialized metabolites with essential roles in chemical defenses against herbivores and pathogens (Banks et al., 2011; Nelson and Werck-Reichhart, 2011; Wurtzel and Kutchan, 2016). Substrate promiscuity has been documented to play a central role in the evolution of plant specialized metabolic enzymes (Weng et al., 2012; Leong and Last, 2017), however most plant P450s are highly substrate-specific (Verpoorte, 2013). Here, we show the rapid inversion of primary and weak secondary (promiscuous) catalytic activities between two distinct yet evolutionarily linked multifunctional P450s, CYP71A12 and CYP71A13, based on intramolecular epistasis of two amino acid residues under positive selection in CYP71A12. Furthermore, we uncover previously undocumented catalytic activity during the inversion as well as naturally occurring amino acid substitution patterns that could have been present in evolutionary intermediates between the two enzymes. Comparative expression profiling and homology modeling reveal that natural selection acted on the promoter of CYP71A13 and the substrate-recognition elements of CYP71A12 to improve the efficiencies of their promiscuous reactions. The rise in catalytic promiscuity potentiated the divergence of new P450 enzyme functions in cyanogenic defense metabolism. Directed evolution of promiscuous reactions is one of the core technologies underpinning the field of synthetic biology. Our results provide a more complete understanding of how natural selection uses promiscuous reactions to generate new enzymes in nature and chemical diversity in pathogen defense, as well as demonstrate a novel strategy for identifying their molecular origins in highly divergent, related enzymes.
IsoformSwitchAnalyzeR: Analysis of changes in genome-wide patterns of alternative splicing and its functional consequences
Authors: Vitting-Seerup Kristoffer , Sandelin Albin
Published: August 2018

Alternative splicing is an important mechanism involved in both health and disease. Recent work highlights the importance of investigating genome-wide changes in patters of splicing and the subsequent functional consequences. Unfortunately current computational methods only support such analysis on a gene-by-gene basis. To fill this gap, we extended IsoformSwitchAnalyzeR thereby enabling analysis of genome-wide changes in both specific types of alternative splicing as well as the predicted functional consequences of the resulting isoform switches. As a case study, we analyzed RNA-seq data from The Cancer Genome Atlas and found systematic changes in both alternative splicing and the consequences of the associated isoform switches.

Availability

Windows, Linux and Mac OS: http://bioconductor.org/packages/IsoformSwitchAnalyzeR.

Contact

KVS: k.vitting.seerup@gmail.com, AS: albin@binf.ku.dk
Optimizing non-invasive sampling of an infectious bat virus
Authors: Giles John R. , Peel Alison J. , Wells Konstans , Plowright Raina K. , McCallum Hamish , Restif Olivier
Published: August 2018

Notable outbreaks of infectious viruses resulting from spillover events from bats have brought much attention to the ecological origins of bat-borne zoonoses, resulting in an increase in ecological and epidemiological studies on bat populations in Africa, Asia, and Australia. The aim of many of these studies is to identify new viral agents with field sampling methods that collect pooled urine samples from large plastic sheets placed under a bat roost. The efficiency of under-roost sampling also makes it an attractive method for gathering roost-level prevalence data. However, the method allows multiple individuals to contribute to a pooled sample, potentially introducing positive bias. To assess the ability of under-roost sampling to accurately estimate viral prevalence, we constructed a probabilistic model to explore the relationship between four sampling designs (quadrant, uniform, stratified, and random) and estimation bias. We modeled bat density and movement with a Poisson cluster process and spatial kernels, and simulated the four underroost sheet sampling designs by manipulating a spatial grid of hexagonal tiles. We performed global sensitivity analyses to identify major sources of estimation bias and provide recommendations for field studies that wish to estimate roost-level prevalence. We found that the quadrant-based design had a positive bias 5–7 times higher than other designs due to spatial auto-correlation among sampling sheets and clustering of bats in the roost. The sampling technique is therefore highly sensitive to viral presence; but lacks specificity, providing poor information regarding dynamics in viral prevalence. Given population sizes of 5000–14000, our simulation results indicate that using a stratified random design to collect 30–40 urine samples from 80–100 sheets, each with an area of 0.75–1m2, would provide sufficient estimation of true prevalence with minimum sampling bias and false negatives. However, acknowledging the general problem of data aggregation, we emphasize that robust inference of true prevalence from field data require information of underpinning roost sizes. Our findings refine our understanding of the underroost sampling technique with the aim of increasing its specificity, and suggest that the method be further developed as an efficient non-invasive sampling technique that provides roost-level estimates of viral prevalence within a bat population.
A modelling exercise to show why population models should incorporate distinct life histories of dispersers
Authors: Deere Jacques A. , van den Berg Ilona , Roth Gregory , Smallegange Isabel M.
Published: August 2018

Dispersal is an important form of movement influencing population dynamics, species distribution, and gene flow between populations. In population models, dispersal is often included in a simplified manner by removing a random proportion of the population. Many ecologists now argue that models should be formulated at the level of individuals instead of the population-level. To fully understand the effects of dispersal on natural systems, it is therefore necessary to incorporate individual-level differences in dispersal behaviour in population models. Here we parameterised an integral projection model (IPM), which allows for studying how individual life histories determine population-level processes, using bulb mites,Rhizoglyphus robini, to assess to what extent dispersal expression (frequency of individuals in the dispersal stage) and dispersal probability affect the proportion of dispersers and natal population growth rate. We find that allowing for life-history differences between resident phenotypes and disperser phenotypes shows that multiple combinations of dispersal probability and dispersal expression can produce the same proportion of leaving individuals. Additionally, a given proportion of dispersing individuals results in different natal population growth rates. The results highlight that dispersal life histories, and the frequency with which disperser phenotypes occur in the natal population, significantly affect population-level processes. Thus, biological realism of dispersal population models can be increased by incorporating the typically observed life history differences between resident phenotypes and disperser phenotypes, and we here present a methodology to do so.
Coding of whisker motion across the mouse face
Authors: Severson Kyle S. , Xu Duo , Yang Hongdian , O’Connor Daniel H.
Published: August 2018

Haptic perception synthesizes touch with proprioception, or sense of body position. Humans and mice alike experience rich active touch of the face. Because most facial muscles lack proprioceptor endings, the sensory basis of facial proprioception remains unsolved. Facial proprioception may instead rely on mechanoreceptors that encode both touch and self-motion. In rodents, whisker mechanoreceptors provide a signal that informs the brain about whisker position. Whisking involves coordinated orofacial movements, so mechanoreceptors innervating facial regions other than whiskers could also provide information about whisking. To define all sources of sensory information about whisking available to the brain, we recorded spikes from mechanoreceptors innervating diverse parts of the face. Whisker motion was encoded best by whisker mechanoreceptors, but also by those innervating whisker pad hairy skin and supraorbital vibrissae. Redundant self-motion responses may provide the brain with a stable proprioceptive signal despite mechanical perturbations such as whisker growth and active touch.
Rapid heuristic inference of antibiotic resistance and susceptibility by genomic neighbor typing
Authors: Břinda Karel , Callendrello Alanna , Ma Kevin C. , MacFadden Derek R , Charalampous Themoula , Lee Robyn S , Cowley Lauren , Wadsworth Crista B , Grad Yonatan H , Kucherov Gregory , O’Grady Justin , Baym Michael , Hanage William P
Published: August 2018

Surveillance of drug-resistant bacteria is essential for healthcare providers to deliver effective empiric antibiotic therapy. However, traditional molecular epidemiology does not typically occur on a timescale that could impact patient treatment and outcomes. Here we present a method called ‘genomic neighbor typing’ for inferring the phenotype of a bacterial sample by identifying its closest relatives in a database of genomes with metadata. We show that this technique can infer antibiotic susceptibility and resistance for both S. pneumoniae and N. gonorrhoeae. We implemented this with rapid k-mer matching, which, when used on Oxford Nanopore MinION data, can run in real time. This resulted in determination of resistance within ten minutes (sens/spec 91%/100% for S. pneumoniae and 81%/100% N. gonorrhoeae from isolates with a representative database) of sequencing starting, and for clinical metagenomic sputum samples (75%/100% for S. pneumoniae), within four hours of sample collection. This flexible approach has wide application to pathogen surveillance and may be used to greatly accelerate appropriate empirical antibiotic treatment.
A model for physiological transmembrane transport derived from thermodynamical principles
Authors: Herrera-Valdez Marco Arieli
Published: August 2018

A generic formulation for both passive and active transmembrane transport is derived from basic thermodynamical principles. The derivation takes into account the energy required for the motion of molecules across membranes, and includes the possibility of modeling asymmetric flow. Transmembrane currents can then be described by the generic model in the case of electrogenic flow. As it is desirable in new models, it is possible to derive other well known expressions for transmembrane currents as particular cases of the generic formulation. For instance, the conductance-based formulation for current turns out to be a linear approximation of the generic current. Also, under suitable assumptions, other formulas for current based on electrodiffusion, like the constant field approximation by Goldman, can also be recovered from the generic formulation. The applicability of the generic formulations is illustrated first with fits to existing data, and after, with models of transmembrane potential dynamics for pacemaking cardiocytes and neurons. The generic formulations presented here provide a common ground for the biophysical study of physiological phenomena that depend on transmembrane transport.
Sleep regulates visual selective attention inDrosophila
Authors: Kirszenblat Leonie , Ertekin Deniz , Goodsell Joseph , Zhou Yanqiong , Shaw Paul J , Swinderen Bruno van
Published: August 2018

Although sleep-deprivation is known to impair attention in humans and other mammals, the underlying reasons are not well understood, and whether similar effects are present in non-mammalian species is not known. We therefore sought to investigate whether sleep is important for optimising attention in an invertebrate species, the genetic modelDrosophila melanogaster. We developed a high-throughput paradigm to measure visual attention in freely-walkingDrosophila, using competing foreground/background visual stimuli. We found that whereas sleep-deprived flies could respond normally to either stimulus alone, they were more distracted by background cues in a visual competition task. Other stressful manipulations such as starvation, heat exposure, and mechanical stress had no effects on visual attention in this paradigm. In contrast to sleep-deprivation, providing additional sleep using the GABA-A agonist 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol (THIP) did not affect attention in wild-type flies, but significantly improved attention in the learning mutantdunce. Our results reveal a key function of sleep in optimising attention processes inDrosophila, and establish a behavioural paradigm that can be used to explore the molecular mechanisms involved.

Summary statement

Sleep deprivation specifically impairs visual selective attention in fruit flies, without affecting behavioural responses to simple visual stimuli.
Fusion pore regulation by Epac2/cAMP controls cargo release during insulin exocytosis
Authors: Gucek Alenka , Gandasi Nikhil R , Omar-Hmeadi Muhmmad , Bakke Marit , Døskeland Stein O. , Tengholm Anders , Barg Sebastian
Published: August 2018

Regulated exocytosis establishes a narrow fusion pore as the initial aqueous connection to the extracellular space, through which small transmitter molecules such as ATP can exit. Co-release of larger peptides and hormones like insulin requires further expansion of the pore. There is evidence that pore expansion is regulated and can fail in type-2 diabetes and neurodegenerative disease. Here we report that the cAMP-sensor Epac2 (Rap-GEF4) controls fusion pore behavior by acutely recruiting two pore-restricting proteins, amisyn and dynamin-1, to the exocytosis site in insulin-secreting beta-cells. cAMP elevation leads to pore expansion and peptide release, but not when Epac2 is inactivated pharmacologically or in Epac2-/- mice. Conversely, overexpression of Epac2 impedes pore expansion. Widely used antidiabetic drugs (GLP-1 agonists and sulfonylureas) activate this pathway and thereby paradoxically restrict hormone release. We conclude that Epac2/cAMP controls fusion pore expansion and thus the balance of hormone and transmitter release during insulin granule exocytosis.
Automated literature mining and hypothesis generation through a network of Medical Subject Headings
Authors: Wilson Stephen Joseph , Wilkins Angela Dawn , Holt Matthew V. , Choi Byung Kwon , Konecki Daniel , Lin Chih-Hsu , Koire Amanda , Chen Yue , Kim Seon-Young , Wang Yi , Wastuwidyaningtyas Brigitta Dewi , Qin Jun , Donehower Lawrence Allen , Lichtarge Olivier
Published: August 2018

The scientific literature is vast, growing, and increasingly specialized, making it difficult to connect disparate observations across subfields. To address this problem, we sought to develop automated hypothesis generation by networking at scale the MeSH terms curated by the National Library of Medicine. The result is a Mesh Term Objective Reasoning (MeTeOR) approach that tallies associations among genes, drugs and diseases from PubMed and predicts new ones.

Comparisons to reference databases and algorithms show MeTeOR tends to be more reliable. We also show that many predictions based on the literature prior to 2014 were published subsequently. In a practical application, we validated experimentally a surprising new association found by MeTeOR between novel Epidermal Growth Factor Receptor (EGFR) associations and CDK2. We conclude that MeTeOR generates useful hypotheses from the literature (http://meteor.lichtargelab.org/).

AUTHOR SUMMARY

The large size and exponential expansion of the scientific literature forms a bottleneck to accessing and understanding published findings. Manual curation and Natural Language Processing (NLP) aim to address this bottleneck by summarizing and disseminating the knowledge within articles as key relationships (e.g. TP53 relates to Cancer). However, these methods compromise on either coverage or accuracy, respectively. To mitigate this compromise, we proposed using manually-assigned keywords (MeSH terms) to extract relationships from the publications and demonstrated a comparable coverage but higher accuracy than current NLP methods. Furthermore, we combined the extracted knowledge with semi-supervised machine learning to create hypotheses to guide future work and discovered a direct interaction between two important cancer genes.
Switch-Like Phosphorylation of WRN Integrates End-Resection with RAD51 Metabolism at Collapsed Replication Forks
Authors: Palermo Valentina , Malacaria Eva , Semproni Maurizio , Perdichizzi Benedetta , Valenzisi Pasquale , Sanchez Massimo , Marini Federica , Pellicioli Achille , Franchitto Annapaola , Pichierri Pietro
Published: August 2018

Replication-dependent DNA double-strand breaks are harmful lesions preferentially repaired by homologous recombination; a process that requires processing of DNA ends to allow RAD51-mediated strand invasion. End-resection and subsequent repair are two intertwined processes, but the mechanism underlying their execution is still poorly appreciated. The WRN helicase is one of the crucial factors for the end-resection and is instrumental to select the proper repair pathway. Here, we reveal that ordered phosphorylation of WRN by the CDK1, ATM and ATR kinases define a complex regulatory layer that is essential for correct long-range end-resection connecting it to repair by homologous recombination. We establish that long-range end-resection requires an ATM-dependent phosphorylation of WRN at Ser1058 and that phosphorylation at Ser1141, together with dephosphorylation at the CDK1 site Ser1133, is needed for the correct metabolism of RAD51 foci and RAD51-dependent repair. Collectively, our findings suggest that regulation of WRN by multiple kinases functions as molecular switch to allow a timely execution of end-resection and repair at replication-dependent DNA double-strand breaks.
Microglial Heterogeneity in a Mouse Model of Alzheimer’s Disease: A Mass Cytometry Analysis
Authors: Fountain EM , Esparza TJ , Malkova O , Oh ST , Brody DL
Published: August 2018

Microglia, the resident immune cells of the central nervous system, have been subject to intense scrutiny recently because of their implicated role in the pathogenesis of Alzheimer’s disease, as well as many other neurological conditions. However, little is known about the diversity of microglial phenotypes, apart from the clear recognition that the M1-M2 distinction is an oversimplification. We used mass cytometry, a high dimensional analog of flow cytometry involving mass spectrometry-based analyses of single cells bound with metal-tagged antibodies, to characterize the diversity of microglia isolated from the brains of 3xTg-AD mice at 12, 18, and 24 months of age. Antibodies to microglial surface antigens CD11b, CD11c, CD14, CD18, CD24, CD35, CD38, CD45, CD51, CD64, CD68, CD86, CD124, CD172a, CD200R, CD206, CD274, CD301, CX3CR1, F4-80, MERTK, MHC class II, Siglec F, and TLR4 as well as intracellular antigens Arginase-1, IL10, IL12p40, iNOS, NADPH Oxidase, TGF-beta, and TNF-alpha were conjugated to unique metal isotopes, and used for mass cytometry. Phenograph-based clustering of the resulting high dimensional datasets identified 28 cell clusters of widely varying sizes, including clearly discrete phenotypes as well as pseudo-continuous/fractal phenotypic diversity. Monte Carlo simulations involving random reshuffling of the datasets revealed very different and much more uniform clustering patterns. Furthermore, control analyses of mouse peripheral blood mononuclear cells and brain microglia using the same markers revealed largely disjoint clusterings, indicating that these microglial clusters were not the result of peripheral blood contamination. Most of the microglial clusters were similar in samples from 3xTg-AD mice at all 3 ages, as well as from 12-month-old wild-type mice. The largest cluster expressed high levels of canonical microglial markers CD11b, CD11c, CD18, CD64, CD68, CD200R, CX3CR1, F4-80, NADPH oxidase, and TGF-beta but did not vary between experimental groups. However, 3 clusters did differ across experimental groups, one of which increased significantly with age in the 3xTg-AD mice as a fraction of the total microglial population. This cluster expressed high levels of CD18, CD38, CD45, CD86, and CD200R, but not other canonical markers. In summary, these mass cytometry-based analyses revealed previously uncharacterized microglial phenotypic heterogeneity in a mouse model of Alzheimer’s disease. The specific roles of the putative subclasses of microglia, their relevance to human disease, and many other questions remain to be addressed.
Non-linear phenotypic variation uncovers the emergence of heterosis inArabidopsis thaliana
Authors: Vasseur François , Fouqueau Louise , Vienne Dominique de , Nidelet Thibault , Violle Cyrille , Weigel Detlef
Published: August 2018

Heterosis describes the phenotypic superiority of hybrids over their parents in traits related to fitness. Understanding and predicting non-additive inheritance such as heterosis is crucial for evolutionary biology, as well as for plant and animal breeding. However, the physiological bases of heterosis remain debated. Moreover, empirical data in various species have shown that diverse genetic and molecular mechanisms are likely to explain heterosis, making it difficult to predict its emergence and amplitude from parental genotypes alone. In this study, we evaluated a model of physiological dominance proposed by Sewall Wright to explain the non-additive inheritance of metabolic fluxes at the cellular level. We used 450 hybrids derived from crosses among natural inbred accessions ofArabidopsis thalianato test Wright’s model for two fitness-related traits at the whole-plant level: growth rate and fruit number. We found that allometric relationships between traits constrain phenotypic variation in hybrids and inbreds to a similar extent. These allometric relationships behave predictably, in a non-linear manner, explaining up to 75% of heterosis amplitude, while genetic distance among parents at best explains 7%. Thus, our findings are consistent with Wright’s model of physiological dominance on plant performance, and suggest that the emergence of heterosis is an intrinsic property of non-linear relationships between traits. Furthermore, our study highlights the potential of a geometric approach of phenotypic relationships for predicting heterosis of two major components of crop productivity and yield.
Food safety assessment in India: modelling enablers
Authors: Shukla Seema , Singh Surya Prakash , Shankar Ravi
Published: August 2018

Purpose

The ever-widening competitive global markets demand food business to demonstrate safe food supplies across the world. The causes of food borne illness are complex to determine and require a careful evaluation of all stages of food supply chain and food safety practices. The purpose of this paper is to systematically investigate the factors responsible for the assessment of food supply chain and evaluation of food safety system in India.

Design/methodology/approach

The study utilizes a combination of qualitative and quantitative approach by exploring expert’s opinion systematically using a semi-structured interview followed by careful grouping of responses using the grounded theory approach to build the research theme. The prioritization of the critical factors is carried out using Pareto analysis. The methodological review was carried out to identify factors and categorize them based on their impact on hierarchical logical relationship using total interpretive structural modeling approach to determine the enablers.

Findings

This paper attempts to deliver an inimitable list of seven vital factors for the effective design of evaluation system for food safety practices. The study provides a careful insight on the issue pertaining to designing of assessment system including competence building for assessor and availability of well-defined technical protocol. The recommendation for developing a robust food safety inspection system by implementing stricter regulation, enhancing competence and design initiatives is provided.

Originality/value

The study provides a unique list of factors for the assessment of food safety practices and develops the relationship. Food safety assessment is an integral part of food safety study which is systematically explored and conceptualized in this paper. The study is carried out using the opinion of Indian experts.
Developing a causal model to evaluate the critical issues in reverse supply chain implementation
Authors: Chakraborty Kaustov , Mondal Sandeep , Mukherjee Kampan
Published: August 2018

Purpose

Approximately, 800m tons of e-waste is generated per year in India. Reverse supply chain (RSC) is the probable strategy to cope up with the issue. Setting up a RSC process is not popular in the Indian sector. There are several factors that basically control the profitability of such kind of business. Hence, the purpose of this paper is to develop a causal model among the identified issues and sub-issues for setting up a RSC in an Indian semiconductor manufacturing industry and then evaluate the critical issues based on the causal relations.

Design/methodology/approach

Decision-making trial and evaluation laboratory (DEMATEL) method along fuzzy set theory is used to develop the causal framework among the identified strategical and tactical issues. According to the causal relations from DEMATEL, analytical network process is then used to identify the weights of the sub-issues.

Findings

The cause–effect interactions among the main issues show that legislations and regulations, market-related issues and organizational issue are the most significant strategic issues. Uncertainty in the acquisition time is the most significant tactical issue because it has a crucial impact on the quality and quantity of the used products. Based on the obtained causal relations of the main issues, it is identified that the reduction of waste, creation of new opportunity, market competition, cost reduction, change in technology and location, capacity and number of recovery facility are the major sub-issues in RSC implementation.

Practical implications

This study is conducted on the basis of the experts’ opinion from a semiconductor manufacturing industry, situated in the southern part of India. Therefore, this proves its practical implications.

Originality/value

The paper provides the detail illustration of the issues in the RSC process, and the prioritization of the issues based on the cause–effect relationships also provides some meaningful managerial insights.
Pathways to workplace innovation and career satisfaction in the public service
Authors: Wipulanusat Warit , Panuwatwanich Kriengsak , Stewart Rodney Anthony
Published: August 2018

Purpose

The purpose of this paper is to study the influence of two climates for innovation constructs, namely, leadership and organisational culture, on workplace innovation and career satisfaction.

Design/methodology/approach

This study used structural equation modelling to test the data from 3,125 engineering professionals in the Australian Public Service (APS).

Findings

The structural model indicated that leadership for innovation and ambidextrous culture for innovation influenced workplace innovation which, in turn, improved career satisfaction. Moreover, modelling revealed a significant relationship between ambidextrous culture for innovation and career satisfaction. This study also investigated mediation effects and revealed both simple and sequential mediation paths in the model. It was found that improving workplace innovation and career satisfaction through recognition of an engineer’s contribution to their agency would assist in retaining and advancing in-house engineering expertise.

Practical implications

The structural model could be used to address current shortages of engineering professionals in the Commonwealth of Australia departments. The findings emphasise the importance of Commonwealth departments providing opportunities for their engineers to engage in creative and innovative projects which enhance their professional career.

Originality/value

This study fills the gap in the innovation literature by exploring the relationships through which socio-psychological factors affect workplace innovation and career satisfaction on the innovation process for engineering professionals in the APS.
Institutionalizing social impact investing: implications for Islamic finance
Authors: Kappen Jeffrey , Mitchell Matthew , Chawla Kavilash
Published: August 2018

Purpose

The purpose of this paper is to examine the institutionalization of screening and metrics in conventional finance and reflect upon the implications for Islamic finance.

Design/methodology/approach

The study involves the analysis of archival data, interviews and fieldwork with current impact investors in North America and the European Union to trace the historical development of impact investing screening and metrics.

Findings

First, the paper explores how conventional investors have applied positive and negative screens in the creation of their values/mission-based investment strategies. This is followed by a historical analysis of the development and implementation of impact metrics and regulatory frameworks that influenced the growth of conventional impact investing. The possible benefits of learning from these experiences for the Islamic finance industry are then considered. The paper concludes with an analysis of the potential value of mission/values-based investing for the economic development of the Middle East and North Africa region.

Research limitations/implications

Though not a comprehensive study of institutionalization, this study supports recent calls for more intentional use of capital for blended returns within Islamic markets. To support these initiatives, it provides scholars and practitioners with multiple recommended points of entry into this growing market.

Originality/value

There has been scant organizational research examining the development of best practices within the impact investment community and how these might be applied to other contexts such as Islamic finance.
George Washington: a revolutionary approach to leadership
Authors: Harris Todd C.
Published: August 2018

Purpose

The purpose of this paper is twofold: first, to examine George Washington’s approach to leadership through the lens of contemporary leadership theory and practice; and second, to help modern managers further reflect upon and develop their own leadership capabilities through a historiographic examination of Washington’s leadership traits and skills.

Design/methodology/approach

Combining three different academic disciplines, management, psychology and history, the author utilized a historiographic and interdisciplinary research methodology, conducting a detailed exploration of the life of George Washington through an examination of a wide range of original archival materials, books, journal articles and other sources.

Findings

The present analysis reveals that Washington demonstrated a variety of well-validated leadership competencies (e.g. emotional intelligence, resilience, integrity, etc.) that are largely consistent with leader-centered theoretical conceptions of leadership.

Originality/value

This is the first historiographic study of George Washington’s approach to leadership within the management literature. Additionally, through the development of a competency model, the study demonstrates how Washington employed tools and techniques from a host of modern leadership theories to achieve critically important results.
Silencing of C3G increases cardiomyocyte survival inhibition and apoptosis via regulation of p‐ERK1/2 and Bax
Authors: Yang Dongyan , Zhang Lei , Zhang Zhisheng , Hu Sulei , Fu Yanbo , Laukkanen Jari A. , Li Gang
Published: August 2018

Experimental studies have shown that overexpression of Rap guanine nucleotide exchange factor 1 (C3G) plays pro‐survival and anti‐apoptotic roles through molecule phosphorylated extracellular signal‐regulated kinase1/2 (p‐ERK1/2) in cardiomyocytes. However, it is still unclear if silencing of C3G may increase cell survival inhibition and apoptosis in cardiomyocytes, and whether C3G silence induced injuries are reduced by the overexpression of C3G through regulation of p‐ERK1/2 and pro‐apoptotic molecule Bax. In this study, the rat‐derived H9C2 cardiomyocytes were infected with C3G small hairpin RNA interference recombinant lentiviruses, which silenced the endogenous C3G expression in the cardiomyocytes. Then, contrary experiments were conducted using C3G overexpression. The cell proliferation and apoptosis were analyzed in the cardiomyocytes which were treated with or without hypoxia/reoxygenation (H/R). Silencing of C3G leaded to significant increase in cell survival inhibition and apoptosis, combined with aggravated the injuries induced by H/R. Overexpression of C3G reduced the injuries induced by the silencing of C3G in the cardiomyocytes via regulation of p‐ERK1/2 and Bax. In conclusion, our results provide new experimental evidence that silencing of C3G can increase cell survival inhibition and apoptosis in cardiomyocytes via regulation of p‐ERK1/2 and Bax.
Assessment of antioxidant capacity by method comparison and amino acid characterisation in buffalo milk kefir
Authors: Ozcan Tulay , Sahin Saliha , Akpinar‐Bayizit Arzu , Yilmaz‐Ersan Lutfiye
Published: August 2018

This study aimed to analyse the antioxidant capacity and total phenolic content of buffalo milk kefir fermented with grains or a commercial starter culture, as well as characterisation of the amino acid profile. During fermentation, the ferrous‐reducing activity of samples increased, while the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and 2,2′‐azino‐bis‐(3‐ethylbenzothiazoline‐6‐sulphonic acid) (ABTS) scavenging activity decreased. The highest value of the ABTS and DPPH scavenging activity was recorded for buffalo milk kefir with grain, which also showed a lower ferric‐reducing antioxidant power during storage. Statistical analyses showed a significant effect of starter culture type and fermentation/storage time on the antioxidant capacity of buffalo kefir.
Severe cutaneous eruptions following the topical use of preparations containing bufexamac: Is it time to reconsider its registration in Australia?
Authors: Harris Adam G , Saikal Samra L , Scurry Jim , Relic John , Nixon Rosemary L , Chee Paul
Published: August 2018

Despite being a well‐recognised cause of allergic contact dermatitis with an embargo in many countries around the world, bufexamac is available over the counter in topical preparations in Australia. We present a series of patients who developed severe cutaneous eruptions after the topical application of bufexamac containing preparations to highlight the potential risks of this medication, as well as advocate for the reconsideration of its registration by the Therapeutic Goods Administration in Australia.
Post‐mortem general surgeon reflection on decision‐making: a mixed‐methods study of mortality audit data
Authors: Cattanach Daniel E. , Wysocki Arkadiusz P. , Ray‐Conde Therese , Nankivell Charles , Allen Jennifer , North John B.
Published: August 2018

Background

Surgical deaths in Australia require the treating surgeon to document the event via a standard report. A section of this report invites surgeons to reflect on changes to management they would initiate in retrospect. This study analyses these reflective statements and categorizes them in an effort to gain insight into reflective learning.

Methods

This audit‐based cross‐sectional study involves patients who died in‐hospital under the care of general surgeons in Queensland, Australia, between July 2007 and December 2016. Retrospective surgeon statements were analysed using both quantitative and qualitative methods.

Results

Of the 2575 surgeons, 459 (18%) indicated they would manage their patient differently in retrospect. Half of these statements (46%) concerned changes to an operative decision. Of this group, most of these concerned either the decision to operate or not (26%), what operation to perform (32%) or earlier timing of surgery (32%). Overall, one‐third of statements (29%) concerned retrospective changes to clinical decisions not related to operative management. Communication considerations, ceiling of care decisions and technical operative changes made up smaller proportions of statements.

Conclusion

This mixed‐methods study has identified a minority of surgeons proffer retrospective management changes after their patient has died. Of those who do, decision‐making around operative management is the most common area of reflective consideration.
A Computational Model of Heat Loss and Water Condensation on the Gas‐Side of Blood Oxygenators
Authors: Gómez Bardón Ricardo , Dubini Gabriele , Pennati Giancarlo
Published: August 2018

Clinical observation of condensation at the gas flow exit of blood oxygenators is a recurrent event during cardiopulmonary bypass. These devices consist of a bundle of hollow fibers made of a microporous membrane that allows the exchange of O2 and CO2. The fibers carry a gas mixture inside (intraluminal flow), while blood flows externally around them (extraluminal flow). Although different studies described this effect in the past, the specific role of the different sections of the device requires further analysis, and the total condensation rate remains unquantified. In this study, a closer look is taken at the transition of gas between the oxygenation bundle and the external room air. A method is proposed to estimate the total condensate output, combining computational fluid dynamics (CFD) of thermal distribution and a simplified 1D model of water vapor saturation of gas. The influence of a number of different parameters is analyzed, regarding material properties, environmental conditions, and clinical use. Results show that condensation rate could vary in a 30‐fold range within reasonably small variations of the different variables considered.
Improved Generalized Predictive Control Algorithm for Blood Glucose Control of Type 1 Diabetes
Authors: Liu Wenping , Zhang Gangping , Yu Liling , Xu Binfeng , Jin Haoyu
Published: August 2018

Artificial pancreas (AP) is an important treatment for patients with Type 1 diabetes (T1D). The control algorithm adopted in an AP system determines its reliability and accuracy. The generalized predictive control (GPC) is a representative adaptive control algorithm and has been widely applied to AP systems. However, we found that the traditional GPC controller does not work well for adolescents with T1D because of their high‐fluctuating blood glucose and high insulin resistance. Here, we propose an improved GPC algorithm with an adaptive reference glucose trajectory and an adaptive softening factor. The slopes of the reference trajectory and the value of softening factor are calculated real‐time on the basis of the blood glucose concentration (BGC) variations. In silico testing was done using the US Food and Drug Administration (FDA) approved virtual patient software T1D mellitus. The BGC trace and density of 20 patient‐subjects (10 adults and 10 adolescents) were recorded. Results showed that the average BGC percentage within the target regions (70–180 mg/dL) of the tests with adaptive reference glucose trajectory and softening factor for adolescents (0.93 ± 0.07) was significantly higher than that of the traditional GPC algorithm tests (0.88 ± 0.11), suggesting that the control quality of the blood glucose of adolescents is significantly improved with our GPC algorithm. Therefore, our improved GPC controller is effective and should have a good applicability in AP systems.
Effects of dietary bamboo vinegar supplementation on performance, eggshell quality, ileal microflora composition, and intestinal villus morphology of laying hens in the late phase of production
Authors: Rattanawut Jessada , Pimpa Opart , Yamauchi Koh‐en
Published: August 2018

This study investigated the effects of bamboo vinegar (BV) supplementation on performance, eggshell quality, ileal microflora, and villus morphology in aged laying hens. A total of 320 hens (70 weeks old) were divided into 4 dietary treatments with 10 replicates of 8 hens each. They were fed a basal diet supplemented withBVat 0%, 0.2%, 0.4%, or 0.8% level until 86 weeks of age. The level ofBVin the diet had no effect on egg performance, feed intake, or feed efficiency (p > 0.10). Damaged egg rate decreased in the hens fed the 0.4% and 0.8%BVdiets during 79–86 weeks of age (p < 0.05). Eggshell thickness and eggshell strength were higher in the hens fed the 0.4% and 0.8%BVdiets at weeks 82 and 86 compared to the controls. In the ileal content, population ofEscherichia coliandSalmonellaspp. decreased with 0.4% and 0.8%BV(p < 0.05). Villus height and areas of duodenum were higher in the hens fed the 0.4% and 0.8%BVdiets (p < 0.05). The results indicate that a level of 0.4%BVin a layer's diet is sufficient for reducing pathogenic bacteria, stimulating intestinal functions and improving eggshell quality of laying hens in the late phase of production.
Inclusive research: An Irish perspective
Authors: Salmon Nancy , Barry Aoife , Hutchins Enid
Published: August 2018

Accessible Summary

We talked to 14 people about what it is like to do inclusive research in the Republic of Ireland.

People said that more time is needed to do inclusive research well. They also told us about how hard it can be for all members of the research team to be equally involved in all research stages.

Learning to speak up for themselves was something people with learning disabilities said they liked about being an inclusive researcher.

Inclusive research teams need to write more about how they work on projects together, to give others ideas about how to do good research that matters to people with learning disabilities.

Background

The United Nations (UN) Convention on the Rights of Persons with Disabilities (CRPD) (United Nations, ) sets the expectation that people with disabilities be involved in research that affects their lives. Inclusive research moves people with intellectual disabilities away from being research subjects, towards power‐balanced research collaborations that can create individual and societal change.

Method

This study employed a qualitative methodology guided by critical disability theory. Participants included seven adults with intellectual disability, two supporters and five academics who all had experience of inclusive research. Semistructured individual interviews (n = 9) and one focus group (n = 5) were carried out to explore experiences of engaging in inclusive research in the Republic of Ireland.

Results

Thematic analysis using Atlas.ti software yielded three themes: “Continuum of inclusive research,” “Value of inclusive research” and “Power relations within inclusive research.” Definitions of inclusive research occurred along a continuum from participatory to emancipatory. Advocating for policy change and personal growth motivated participants to become inclusive researchers. The power dynamics negotiated by teams functioning within academic environments were highlighted, yet despite this, inclusive research teams are creating a space where people with intellectual disabilities are becoming confident researchers and peer mentors.

Conclusions

This study illuminated experiences of engaging in inclusive research in an Irish context. Retaining a responsive, local approach to inclusive research is advised. Being part of inclusive research teams was both personally rewarding and financially complex. Inclusive research is at a critical moment in Ireland, poised to effect positive change in policy and service provision. Critically reviewing and documenting how inclusive research teams negotiate these complex dynamics is warranted.
3′‐Sialyllactose as an inhibitor of p65 phosphorylation ameliorates the progression of experimental rheumatoid arthritis
Authors: Kang Li‐Jung , Kwon Eun‐Soo , Lee Kwang Min , Cho Chanmi , Lee Jae‐In , Ryu Young Bae , Youm Tae Hyun , Jeon Jimin , Cho Mi Ra , Jeong Seon‐Yong , Lee Sang‐Rae , Kim Wook , Yang Siyoung
Published: August 2018

Background and Purpose

3′‐Sialyllactose (3′‐SL) is a safe compound that is present in high levels in human milk. Although it has anti‐inflammatory properties and supports immune homeostasis, its effect on collagen‐induced arthritis (CIA) is unknown. In this study, we investigated the prophylactic and therapeutic effect of 3′‐SL on the progression of rheumatoid arthritis (RA) in in vitro and in vivo models.

Experimental Approach

The anti‐arthritic effect of 3′‐SL was analysed with fibroblast‐like synoviocytes in vitro and an in vivo mouse model of CIA. RT‐PCR, Western blotting and ELISA were performed to evaluate its effects in vitro. Histological analysis of ankle and knee joints of mice with CIA was performed using immunohistochemistry, as well as safranin‐O and haematoxylin staining.

Key Results

3′‐SL markedly alleviated the severity of CIA in the mice by reducing paw swelling, clinical scores, incidence rate, serum levels of inflammatory cytokines and autoantibody production. Moreover, 3′‐SL reduced synovitis and pannus formation and suppressed cartilage destruction by blocking secretion of chemokines, pro‐inflammatory cytokines, matrix metalloproteinases and osteoclastogenesis via NF‐κB signalling. Notably, phosphorylation of p65, which is a key protein in the NF‐κB signalling pathway, was totally blocked by 3′‐SL in the RA models.

Conclusions and Implications

3′‐SL ameliorated pathogenesis of CIA by suppressing catabolic factor expression, proliferation of inflammatory immune cells and osteoclastogenesis. These effects were mediated via blockade of the NF‐κB signalling pathway. Therefore, 3′‐SL exerted prophylactic and therapeutic effects and could be a novel therapeutic agent for the treatment of RA.