bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural determinants of protocadherin-15 elasticity and function in inner-ear mechanotransduction
Authors: Choudhary Deepanshu , Narui Yoshie , Neel Brandon L. , Wimalasena Lahiru N. , Klanseck Carissa F. , De-la-Torre Pedro , Chen Conghui , Araya-Secchi Raul , Tamilselvan Elakkiya , Sotomayor Marcos
Published: July 2019

Protocadherin-15 (PCDH15), an atypical member of the cadherin superfamily, is essential for vertebrate hearing and its dysfunction has been associated with deafness and progressive blindness. The PCDH15 ectodomain, made of eleven extracellular cadherin (EC1-11) repeats and a membrane adjacent domain (MAD12), assembles as a parallel homodimer that interacts with cadherin-23 (CDH23) to form the tip link, a fine filament necessary for inner-ear mechanotransduction. Here we report X-ray crystal structures of a PCDH15 + CDH23 heterotetrameric complex and ten PCDH15 fragments that were used to build complete high-resolution models of the monomeric PCDH15 ectodomain. Using molecular dynamics (MD) simulations and validated crystal contacts we propose models for complete PCDH15 parallel homodimers and the tip-link bond. Steered MD simulations of these models predict their strength and suggest conditions in which a multimodal PCDH15 ectodomain can act as a stiff or soft gating spring. These results provide a detailed view of the first molecular steps in inner-ear sensory transduction.
Measuring the host-seeking ability of Aedes aegypti destined for field release
Authors: Lau Meng-Jia , Endersby-Harshman Nancy M. , Axford Jason K. , Ritchie Scott A. , Hoffmann Ary A. , Ross Perran A.
Published: July 2019

Host-seeking is an essential process in mosquito reproduction. Field releases of modified mosquitoes for population transformation rely on successful host-seeking by female mosquitoes, but host-seeking ability is rarely tested in a realistic context. We tested the host-seeking ability of female Aedes aegypti mosquitoes using a semi-field system. Females with different Wolbachia infection types (wMel-, wAlbB-infected and uninfected) or from different origins (laboratory and field) were released at one end of a semi-field cage and recaptured as they landed on human experimenters fifteen meters away. Mosquitoes from each population were then identified with molecular tools or through marking with a consistent weight of fluorescent powder. Wolbachia-infected and uninfected populations had similar average durations to landing and overall recapture proportions, as did laboratory and field-sourced A. aegypti. These results suggest that the host-seeking ability of mosquitoes is not negatively affected by Wolbachia infection or long-term laboratory maintenance. This method provides an approach to study the host-seeking ability of mosquitoes across a long distance which will be useful when evaluating strains of mosquitoes that are planned for releases into the field to suppress arbovirus transmission. An adjustment of this method may also be useful in sterile insect release programs because male host-seeking and swarming around female feeding sites can also be investigated.
Synthetic Genetic Codes Designed to Hinder Evolution
Authors: Calles Jonathan , Justice Isaac , Brinkley Detravious , Garcia Alexa , Endy Drew
Published: July 2019

One challenge in engineering organisms is guaranteeing system behavior over many generations. Spontaneous mutations that arise before or during use can impact heterologous genetic functions, disrupt system integration, or change organism phenotype. Here, we propose restructuring the genetic code itself such that all point mutations in protein-coding sequences are selected against. Synthetic genetic systems so-encoded should “fail safely” in response to many individual spontaneous mutations. We designed a family of such fail-safe codes and analyzed their expected effect on the evolution of engineered organisms via simulation. We predict that fail-safe codes supporting expression of 20 or 15 amino acids could slow the evolution of proteins in so-encoded organisms to 30% or 0% the rate of standard-code organisms, respectively. We also designed quadruplet-codon codes that should be capable of encoding at least 20 amino acids while ensuring all single point mutations in protein-coding sequences are selected against. We show by in vitro experiments that a reduced set of 21 tRNA is capable of expressing a protein whose coding sequence is recoded to use a fail-safe code, whereas a standard-code encoding is not expressed. Our work suggests that a rationally depleted but otherwise natural translation system should yield biological systems with intrinsically reduced evolutionary capacity, and that so-encoded hypoevolvable organisms might be less likely to invade new niches or outcompete native populations.
ORP5/8 AND MIB/MICOS LINK ER-MITOCHONDRIA AND INTRAMITOCHONDRIAL CONTACTS FOR NON-VESICULAR TRANSPORT OF PHOSPHATIDYLSERINE
Authors: Monteiro-Cardoso Vera F. , Rochin Leila , Arora Amita , Houcine Audrey , Jääskeläinen Eeva , Kivelä Annukka M. , Sauvanet Cécile , Bars Romain Le , Marien Eyra , Dehairs Jonas , Neveu Julie , Khallouki Naima El , Santonico Elena , Swinnen Johannes V. , Tareste David , Olkkonen Vesa M. , Giordano Francesca
Published: July 2019

Mitochondria are dynamic organelles essential for cell survival whose structural and functional integrity rely on selective and regulated transport of lipids from/to the endoplasmic reticulum (ER) and across the mitochondrial intermembrane space. As they are not connected by vesicular transport, the exchange of lipids between ER and mitochondria occurs at sites of close organelle apposition called membrane contact sites. However, the mechanisms and proteins involved in these processes are only beginning to emerge. Here, we show that the main physiological localization of the lipid transfer proteins ORP5 and ORP8 is at mitochondria-associated ER membranes (MAMs) subdomains, physically linked to the MIB/MICOS complexes that bridge the two mitochondrial membranes. We also show that ORP5/8 mediate non-vesicular transport of phosphatidylserine (PS) lipids from the ER to mitochondria by cooperating with the MIB/MICOS complexes. Overall our study reveals a novel physical and functional link between ER-mitochondria contacts involved in lipid transfer and intra-mitochondrial membranes contacts maintained by the MIB/MICOS complexes.
Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress
Authors: Buchwalter Abigail , Schulte Roberta , Tsai Hsiao , Capitanio Juliana , Hetzer Martin
Published: July 2019

The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM’s unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs.
Homeoprotein neuroprotection of embryonic neuronal cells
Authors: Vargas Abonce Stephanie E. , Leboeuf Mélanie , Prochiantz Alain , Moya Kenneth L.
Published: July 2019

Most homeoprotein transcription factors have a highly conserved internalization domain used in intercellular transfer. Internalization of homeoproteins ENGRAILED1 or ENGRAILED2 promotes the survival of adult dopaminergic cells, whereas that of OTX2 protects adult retinal ganglion cells. Here we characterize thein vitroneuroprotective activity of several homeoproteins in response to H2O2. Protection is observed with ENGRAILED1, ENGRAILED2, OTX2, GBX2 and LHX9 on midbrain and striatal embryonic neurons whereas cell-permeable c-MYC shows no protective effects. Therefore, five homeoproteins belonging to 3 different classes (ANTENNAPEDIA, PAIRED and LIM) share the ability to protect embryonic neurons from midbrain and striatum. Because midbrain and striatal neurons do not express the same repertoire of the 4 proteins, a lack of neuronal specificity together with a general protective activity can be proposed. In contrast, hEN1 and GBX2 exerted no protection on non-neuronal cells including mouse embryo fibroblasts, macrophages or HeLa cells. For the 4 proteins, protection against cell-death correlated with a reduction in the number of H2O2-induced DNA break foci in midbrain and striatal neurons. In conclusion, within the limit of the number of cell types and homeoproteins tested, homeoprotein protection against oxidative stress-induced DNA breaks and death is specific to neurons but shows no homeoprotein or neuronal type specificity.

SIGNIFICANCE STATEMENT

Homeoproteins are DNA binding proteins regulating gene expression throughout life. Many of them transfer between cells and are thus internalized by live cells. This has allowed for their use as therapeutic proteins in animal models of Parkinson disease and glaucoma. Part of their therapeutic activity is through a protection against neuronal death. Here we show that internalized homeoproteins from three different classes protect embryonic ventral midbrain and striatal neurons from oxidative stress, both at the level of DNA damage and survival. The interest of this finding is that it lends weight to the possibility that many homeoproteins play a role in neuroprotection through shared mechanisms involving, in particular, DNA protection against stress-induced breaks.
Long-term cognitive impairment without diffuse axonal injury following repetitive mild traumatic brain injury in rats
Authors: Tadepalli Sai Ambika , Bali Zsolt Kristóf , Bruszt Nóra , Nagy Lili Veronika , Amrein Krisztina , Fazekas Bálint , Büki András , Czeiter Endre , Hernádi István
Published: July 2019

Repetitive mild traumatic brain injuries (TBI) impair cognitive abilities and increase risk of neurodegenerative disorders in humans. We developed two repetitive mild TBI models in rats with different time intervals between successive weight-drop injuries, and assessed cognitive performance and biomarker profiles. Rats were subjected to repetitive Sham (no injury), single mild (mTBI), repetitive mild (rmTBI – 5 hits, 24 h apart), rapid repetitive mild (rapTBI – 5 hits, 5 min apart) and single severe (sTBI) TBI. We assessed cognitive performance 2 and 8 weeks after TBI in the novel object recognition test (NOR), and 6-7 weeks after TBI in the water maze (MWM). Acute immunohistochemical markers were checked 24 h after TBI, and blood biomarkers were measured with ELISA 8 weeks after TBI. In the NOR, both rmTBI and rapTBI showed poor performance at 2 weeks post-injury. At 8 weeks post-injury, the rmTBI group still performed worse than the Sham and mTBI groups, while the rapTBI group recovered. In the MWM, the rapTBI group performed worse than Sham and mTBI. Acute APP and RMO-14 immunohistochemistry showed axonal injury at the pontomedullary junction in the sTBI, but not in other groups. ELISA showed increased serum GFAP levels 8 weeks after sTBI, while no differences were found between the injury groups in the levels of phosphorylated-tau and S100β. Results suggest that the rmTBI protocol is the most suitable model for testing cognitive impairment after mild repetitive head injuries. The lack of common biomarkers suggests novel unknown underlying mechanisms of rmTBI.
Two-way microscale interactions between immigrant bacteria and plant leaf microbiota as revealed by live imaging
Authors: Steinberg Shifra , Grinberg Maor , Beitelman Michael , Peixoto Julianna , Orevi Tomer , Kashtan Nadav
Published: July 2019

The phyllosphere – the aerial parts of plants – is an important microbial habitat that is home to diverse microbial communities. The spatial organization of bacterial cells on leaf surfaces is non-random, and correlates with leaf microscopic features. Yet, the role of microscale interactions between bacterial cells therein is not well understood. Here, we ask how interactions between immigrant bacteria and resident microbiota affect the spatial organization of the combined community. By means of live imaging in a simplified in vitro system, we studied the spatial organization, at the micrometer scale, of the bio-control agent Pseudomonas fluorescens A506 and the plant pathogen P. syringae B728a when introduced to pear and bean leaf microbiota (the corresponding native plants of these strains). We found significant co-localization of immigrant and resident microbial cells at distances of a few micrometers, for both strains. Interestingly, this co-localization was in part due to preferential attachment of microbiota cells near newly formed P. fluorescens aggregates. Our results indicate that two-way immigrant bacteria – resident microbiota interactions affect the leaf’s microscale spatial organization, and possibly that of other surface-related microbial communities.
Relationship between depressive symptoms and cumulative 24-hour urinary norepinephrine excretion level among undergraduate medical students in Uganda
Authors: Owoola-Ajirotutu Mutiat O , Okpanachi Alfred O , Owoola Akeem G , Rukundo Godfrey Z , Yusuf Sadiq
Published: July 2019

Background

Depression is a serious mental health problem in different parts of the world and has been reported to be rising among undergraduate medical students. The incidence of depression has not only been linked to psychosocial factors but also to biological factors, such as altered urinary levels of norepinephrine. This study was carried out to determine the prevalence of depression among undergraduate medical students in Uganda and examine the relationship between depressive symptoms and 24-hour urinary norepinephrine excretion levels in the participants.

Methods

One hundred and sixteen undergraduate medical students (75 males and 41 females) of Kampala International University, in southwestern Uganda were evaluated for depression using the 21-item Beck Depression Inventory-II (BDI) questionnaire. Twenty-four-hour urine collections from each participant were assayed for norepinephrine excretion levels. Descriptive statistics and Pearson correlation coefficient were computed to examine the data obtained.

Results

The results of this study showed that, a total of 33 participants (28.4%) have depressive symptoms. Students with depressive symptoms had higher but not significant 24-hour urinary mean norepinephrine excretion levels than those without depressive symptoms (121.97±51.48μg/day Vs 87.58±18.64 μg/day, P>0.05). There was a positive weak relationship between BDI scores and 24-hour urinary norepinephrine levels (r= 0.21, p = 0.28). Regression models accounting for socio-demographic characteristics indicated that, type of accommodation, marital status, relationship with parents, educational sponsorship may be risk factors for depressive symptoms observed in the participants.

Conclusions

These results suggest that increased urinary norepinephrine excretion and other psychosocial factors may be associated with depressive symptoms. Measurements of 24-hour urinary norepinephrine excretion may serve as an integrative parameter in diagnosing and management of patients with depression.
Short-term reciprocity in macaque’s social decision-making
Authors: Ballesta S. , Reymond G. , Duhamel J-R.
Published: July 2019

Primates live in complex social environments, where individuals create meaningful networks by adapting their behavior according to past experiences with others. Although free-ranging primates do show signs of reciprocity, experiments in more controlled environments have mainly failed to reproduce such social dynamics. Hence, the cognitive and neural processes allowing monkeys to reciprocate during social exchanges remains elusive. Here, pairs of long-tailed macaques (Macaca fascicularis) took turns into a social decision task involving the delivery of positive (juice reward) or negative (airpuff) outcomes. By analyzing the contingencies of one partner’s past decisions on the other’s future decisions, we demonstrate the presence of reciprocity, but only for the exchange of negative outcomes. Importantly, to display this decisional bias, the monkey needs to witness its partner’s decisions, since non-social deliveries of the same outcome did not have such effect. Withholding of negative outcomes also predicted future social decisions, which suggest that the observed tit-for-tat strategy may not only be motivated by retaliation after receiving an airpuff but also by the gratefulness of not having received one. These results clarify the apparent dichotomy within the scientific literature of reciprocity in non-human primates and suggest that their social cognition comprise revenge and gratitude.
Structural changes during water-mediated amorphization of semiconducting two-dimensional thiostannates
Authors: Hvid Mathias S. , Jeppesen Henrik S. , Miola Matteo , Lamagni Paolo , Su Ren , Jensen Kirsten M. Ø. , Lock Nina
Published: July 2019

Owing to their combined open-framework structures and semiconducting properties, two-dimensional thiostannates show great potential for catalytic and sensing applications. One such class of crystalline materials consists of porous polymeric [Sn3S7
2−]
n
sheets with molecular cations embedded in-between. The compounds are denoted R-SnS-1, where R is the cation. Dependent on the cation, some R-SnS-1 thiostannates transition into amorphous phases upon dispersion in water. Knowledge about the fundamental chemical properties of the thiostannates, including their water stability and the nature of the amorphous products, has not yet been established. This paper presents a time-resolved study of the transition from the crystalline to the amorphous phase of two violet-light absorbing thiostannates, i.e. AEPz-SnS-1 [AEPz = 1-(2-aminoethyl)piperazine] and trenH-SnS-1 [tren = tris(2-aminoethyl)amine]. X-ray total scattering data and pair distribution function analysis reveal no change in the local intralayer coordination during the amorphization. However, a rapid decrease in the crystalline domain sizes upon suspension in water is demonstrated. Although scanning electron microscopy shows no significant decrease of the micrometre-sized particles, transmission electron microscopy reveals the formation of small particles (∼200–400 nm) in addition to the larger particles. The amorphization is associated with disorder of the thiostannate nanosheet stacking. For example, an average decrease in the interlayer distance (from 19.0 to 15.6 Å) is connected to the substantial loss of the organic components as shown by elemental analysis and X-ray photoelectron spectroscopy. Despite the structural changes, the light absorption properties of the amorphisized R-SnS-1 compounds remain intact, which is encouraging for future water-based applications of such materials.
Cryo-EM structure of the CFA/I pilus rod
Authors: Zheng Weili , Andersson Magnus , Mortezaei Narges , Bullitt Esther , Egelman Edward
Published: July 2019

EnterotoxigenicEscherichia coli(ETEC) are common agents of diarrhea for travelers and a major cause of mortality in children in developing countries. To attach to intestinal cells ETEC express colonization factors, among them CFA/I, which are the most prevalent factors and are the archetypical representative of class 5 pili. The helical quaternary structure of CFA/I can be unwound under tensile force and it has been shown that this mechanical property helps bacteria to withstand shear forces from fluid motion. We report in this work the CFA/I pilus structure at 4.3 Å resolution from electron cryomicroscopy (cryo-EM) data, and report details of the donor strand complementation. The CfaB pilins modeled into the cryo-EM map allow us to identify the buried surface area between subunits, and these regions are correlated to quaternary structural stability in class 5 and chaperone–usher pili. In addition, from the model built using the EM structure we also predicted that residue 13 (proline) of the N-terminal β-strand could have a major impact on the filament's structural stability. Therefore, we used optical tweezers to measure and compare the stability of the quaternary structure of wild type CFA/I and a point-mutated CFA/I with a propensity for unwinding. We found that pili with this mutated CFA/I require a lower force to unwind, supporting our hypothesis that Pro13 is important for structural stability. The high-resolution CFA/I pilus structure presented in this work and the analysis of structural stability will be useful for the development of novel antimicrobial drugs that target adhesion pili needed for initial attachment and sustained adhesion of ETEC.
Understanding social impact of data on local communities
Authors: Yoon Ayoung , Copeland Andrea
Published: July 2019

Purpose

The purpose of this paper is to understand the social impact of data on communities from cases of community data utilization.

Design/methodology/approach

This study took an interpretive qualitative approach and conducted a semi-structured phone interview with 45 participants from data intermediaries and local community organizations.

Findings

The results demonstrate both direct and indirect impacts of data on local levels, including resolving local problems from data-driven decisions, realizing unknown problems or correcting misrepresented problems, changing community data practices, strengthening community identity and enhancing the community’s data skills.

Practical implications

The research shows that communities’ data utilization supported community-led actions and initiatives from the bottom-up perspective, which demonstrates the need for supporting communities’ data work.

Social implications

Minimizing inequality in data utilization should be resolved so that all communities can benefit from the power of data.

Originality/value

By demonstrating evidence of data being critical to encouraging communities’ data utilization, this study fills the gap in existing research, which lacks a clear explanation for how the potential of data can be realized at the local level.
Modeling the performance of healthcare construction projects
Authors: Iskandar Karim A. , Hanna Awad S. , Lotfallah Wafik
Published: July 2019

Purpose

Healthcare-sector projects are some of the most complex in modern practice due to their reliance on high-tech components and the level of precision they must maintain. Existing literature in healthcare performance specifically is scarce, but there is a recent increasing trend in both healthcare construction and a corresponding trend in related literature. No previously existing study has derived weights (relative importance) of performance metric in an objective, data-based manner. The purpose of this paper is to present a newly developed mathematical model that derives these weights, free of subjectivity that is common in other literature.

Design/methodology/approach

This paper’s model considers 17 exceptional projects and 19 average projects, and reveals the weights (or relative importance) of ten performance metrics by comparing how projects relate to one another in terms of each metric individually. It solves an eigenvalue problem that maximizes the difference between average and exceptional project performances.

Findings

The most significant weight, i.e. the performance metric which has the greatest impact on healthcare project performance, was request for information per million dollars with a weight of 16.07 percent. Other highly weighted metrics included construction speed and schedule growth at 13.08 and 12.23 percent, respectively. Rework was the least significant metric at 3.61 percent, but not all metrics of quality had low ratings. Deficiency issues per million dollars was weighted at 11.61 percent, for example. All weights derived by the model in this paper were validated statistically to ensure their applicability as comparison and assessment tools.

Originality/value

There is no widely accepted measure of project performance specific to healthcare construction. This study’s contribution to the body of knowledge is its mathematical model which is a landmark effort to develop a single, objective, unified project performance index for healthcare construction. Furthermore, this unified score presents a user-friendly avenue for contractors to standardize their productivity tracking – a missing piece in the practices of many contractors.
Supporting work–life balance with the use of coworking spaces
Authors: Orel Marko
Published: July 2019

Purpose

The purpose of this paper is to investigate the topic of parents who work on a flexible basis and use coworking facilities to find a work–life balance and overcome work–family conflicts.

Design/methodology/approach

The author uses a qualitative approach to explore the research questions. The first part of the empirical research undertakes an ethnographical approach in carrying out the unobstructed participant observation within five European coworking spaces targeted at improving comprehension of the spaces’ mediation mechanisms and development of supportive interactions. The second part traverses into conducting unstructured interviews with parents who work on a flexible basis and use a coworking space as their daily workplace.

Findings

This research paper reveals that flexible workers who found themselves juggling work tasks and family obligations tend to seek better conditions that assist them in tackling conflictual situations and, in addition, enhance their social lives to create further career opportunities. Coworking spaces are thus perceived as optimal workplaces by working parents in that they can find stability and scale their social networks within. Moreover, the continually evolving user interactions resulting from effective mediation mechanisms let these individuals find emotional support, increase productivity and exchange knowledge.

Originality/value

While the coworking industry is rapidly evolving and the academia is keener on investigating the field, the subcategory of work–life and family care within these collaborative environments is virtually unresearched. This paper provides valuable insight into the topic and serves as a knowledge base for the future exploration of this field.
Investigation of sewing and water repellent performance of outdoor clothing
Authors: Erayman Yüksel Yaşar , Korkmaz Yasemin
Published: July 2019

Purpose

Durability of textile materials under wet conditions has become very important in recent years. The water repellency performance of fabrics should be maintained in the seam areas. The purpose of this paper is to analyze the effect of water repellent agents and sewing threads on the seam and water repellency performance properties of woven fabrics.

Design/methodology/approach

100 percent polyester woven fabrics were treated with three different water repellent finishing agents (silicone, fluorocarbons with 6 and 8 carbons) and then sewn with different sewing threads (unfinished/water repellent finished polyester/cotton corespun and polyamide filament). Afterwards, mechanical properties, seam performance and water repellency properties of these materials were measured.

Findings

The effect of finishing which was statistically significant on seam strength only in warp direction was significant on seam elongation and efficiency in both warp and weft directions. Seam strength, seam efficiency, seam slippage and seam pucker of fabrics sewn with polyamide threads were higher than others. The fluorocarbons applied to the fabrics gave higher water repellency values than silicones. In addition, as the chain length increased in fluorocarbons, water repellency performance increased. Sewing process reduced water resistance of fabrics; however, water repellent finish applied to the threads increased water resistance of fabrics.

Originality/value

As a result of the literature review, it was seen that water repellency property of a wear were studied in only seamless areas of fabrics. Originality of this study is that the water repellency properties are also analyzed in the seam areas of the fabrics and evaluated together with the seam performance characteristics.
Clusters and communities: raising the bar towards open innovation 2.0 paradigms
Authors: Tamburis Oscar , Bonacci Isabella
Published: July 2019

Purpose

The growing success of open innovation practices in many firms raises the question of whether such principles can be transferred for reinventing public sector organisations. A paradigm based on principles of integrated collaboration, co-created shared value, cultivated innovation ecosystems, unleashed exponential technologies and extraordinarily rapid adoption is the so-called Open Innovation 2.0. The development of this approach reflects the perception that the innovation process has evolved. This study aims to explore new ways to study healthcare networks as key tool for innovation creation and spreading, by deploying the emergent paradigm of Open Innovation 2.0.

Design/methodology/approach

The study investigates the impact of clusters, or localised networks, involving industrial, academic and institutional players, in the (bio)pharmaceutical setting; the aim is to enrich the line of inquiry into cluster-based innovation by applying a social network analysis (SNA) methodology, with the aim to provide new perspectives for recognising how the set of interactions and relationships in the (bio)pharmaceutical context can lead to higher levels of knowledge transfer, organisational learning and innovation spreading.

Findings

Starting from the top ten (bio)pharmaceutical companies, and the top ten contract research organisations (CROs), the study helps understand that: the combination of the single big pharma company and the CROs to which great part of the work is externalised, can be compared to a community of transaction that deals with the supply and demand of a specific kind of goods and services; clusters can comprise either a single one or more communities of transaction; virtual CROs act as a community whose all components participate to the creation of value (co-creation), thus comparable to a certain extent to a community of fantasy.

Originality/value

Based on the novelty of the OI2/SNA combination approach to deal with the “complex” (bio)pharmaceutical industry, the outcomes of the present study mean to highlight: a comprehensive perspective for understanding the dynamics of modularity and their implications for innovation networks; the presence of innovation networks as main mean to promote and support paths of knowledge creation and transfer.
Leader psychopathy and organizational deviance
Authors: Erkutlu Hakan , Chafra Jamel
Published: July 2019

Purpose

The purpose of this paper is to analyze the relationship between leader psychopathy and organizational deviance. In particular, the authors introduce employee’s psychological safety as the mediator. Furthermore, the moderating role of moral disengagement in the relationship between leader psychopathy and organizational deviance is also considered.

Design/methodology/approach

The data of this study include 611 certified nurses from 9 university hospitals in Turkey. The proposed model was tested by using hierarchical multiple regression analysis.

Findings

The results of this study supported the positive effect of leader psychopathy on organizational deviance along with the mediating effect of employee’s psychological safety. Furthermore, when the level of moral disengagement is low, the relationship between leader psychopathy and organizational deviance is weak, whereas the effect is strong when the level of moral disengagement is high.

Practical implications

The findings of the study recommend that administrators in the healthcare industry ought to be sensitive in treating their subordinates, since it will result in positive organizational relationship, which, subsequently, will certainly reduce organizational deviance. Furthermore, they have to pay more focus on the buffering role of moral disengagement for all those subordinates with high distrust and displaying organizational deviance.

Originality/value

This paper contributes to the literature about workplace deviance by uncovering the relational mechanism between leader psychopathy and employee organizational deviance. Furthermore, it includes practical assistance to healthcare employees and their leaders interested in building trust, increasing leader–employee relationship and reducing organizational deviance.
Antibacterial evaluation of activated carbon cloth with Ag+impregnated with ZnO nanoparticles
Authors: Sharifuddin Sharifatul Ain Binti , Ismail Salwani Binti , Abdullah Imran , Mohamad Irfan , Shaikh Mohammed Javeed
Published: July 2019

Purpose

Staphylococcus aureus(S. aureus),Klebsiella pneumoniae(K. pneumoniae) andStreptococcus pneumoniae(S. pneumoniae) are among the pathogens detected during Hajj pilgrimage known to cause pneumonia. This study aims to evaluate the antibacterial activity of activated carbon cloth (ACC) with Ag+impregnated with zinc oxide nanoparticles (ZnO NPs) against these pathogens.

Design/methodology/approach

ZnO NPs were impregnated into ACC-Ag+via layer-by-layer (LbL) self-assembly. Scanning electron microscope (SEM) was used to observe the fine surface morphological details of the ACC-Ag+-ZnO sheets. Antibacterial activity of the ACC-Ag+-ZnO sheets was evaluated using the disk-diffusion susceptibility assay. Allergy patch test was done to evaluate allergic reactions of the ACC-Ag+-ZnO sheets on human skin.

Findings

SEM micrographs showed successful impregnation of ZnO NPs into the ACC-Ag+sheets. Disk-diffusion susceptibility assay results of ACC-Ag+-ZnO sheets againstS. aureus,K. pneumoniaeandS. pneumoniaeshowed good antibacterial activity; with 1.82 ± 0.13 mm zone of inhibition forS. pneumoniae, at a ZnO concentration of 0.78 mg mL-1. No signs of human skin irritation were observed throughout the allergy patch test.

Originality/value

Results indicate that ACC-Ag+-ZnO sheets could potentially be embedded within surgical face masks (pilgrims’ preferred) to reduce the risks involved with the transmission of respiratory tract infections during and after mass gatherings (e.g. Hajj/Umrah, Olympics).
Professional collaboration between class teachers and special educators in Swedish rural schools
Authors: Pettersson Gerd , Ström Kristina
Published: July 2019

The purpose of this study was to shed light on how work‐related teacher support in the form of special educational consultation can promote the professional development of teachers working in rural schools located in sparsely populated areas. The phenomenon studied was professional collaboration between class teachers and special educators in the context of special educational consultation. The empirical data were collected through interviews and observations in three rural schools in the northern part of Sweden. The findings indicate that special educational consultation is perceived as support and collaboration. The class teachers appreciate the support they receive from special educators. The collaboration is characterised by professional exchange and mutual problem solving. Distributed expertise seems to be a crucial element of the collaboration. The conclusion is that collaborative special educational consultation enables class teachers to support pupils with special educational needs and strengthens professional collaboration between class teachers and special educators.
Protective effects of bifidobacteria against enteropathogens
Authors: Aw Wanping , Fukuda Shinji
Published: July 2019

Recent major advances in metagenomics and metabolomics technologies have enabled us to collect more data on the gut microbiome and metabolome to evaluate its influence on host health. In this short opinion article, we have chosen to focus on summarizing the protective mechanisms of bifidobacteria, a highly regarded probiotic, and it's metabolite: acetate; against enteropathogens, specifically in the E. coli O157:H7 mice model. We advocate for using a novel approach metabologenomics, which is an integration of metagenomic and metabolomic information on a systems biology‐wide approach to better understand this interplay between gut microbiome and host metabolism.
Different Effects of Knockouts in ALDH2 and ACSS2 on Embryonic Stem Cell Differentiation
Authors: Serio Ryan N. , Lu Changyuan , Gross Steven S. , Gudas Lorraine J.
Published: July 2019

Background

Ethanol (EtOH) is a teratogen that causes severe birth defects, but the mechanisms by which EtOH affects stem cell differentiation are unclear. Our goal here is to examine the effects of EtOH and its metabolites, acetaldehyde (AcH) and acetate, on embryonic stem cell (ESC) differentiation.

Methods

We designed ESC lines in which aldehyde dehydrogenase (ALDH2, NCBI#11669) and acyl‐CoA synthetase short‐chain family member 2 (ACSS2, NCBI#60525) were knocked out by CRISPR‐Cas9 technology. We selected these genes because of their key roles in EtOH oxidation in order to dissect the effects of EtOH metabolism on differentiation.

Results

By using kinetic assays, we confirmed that AcH is primarily oxidized by ALDH2 rather than ALDH1A2. We found increases in mRNAs of differentiation‐associated genes (Hoxa1, Cyp26a1, and RARβ2) upon EtOH treatment of WT and Acss2−/− ESCs, but not Aldh2−/− ESCs. The absence of ALDH2 reduced mRNAs of some pluripotency factors (Nanog, Sox2, and Klf4). Treatment of WT ESCs with AcH or 4‐hydroxynonenal (4‐HNE), another substrate of ALDH2, increased differentiation‐associated transcripts compared to levels in untreated cells. mRNAs of genes involved in retinoic acid (RA) synthesis (Stra6 and Rdh10) were also increased by EtOH, AcH, and 4‐HNE treatment. Retinoic acid receptor‐γ (RARγ) is required for both EtOH‐ and AcH‐mediated increases in Hoxa1 and Stra6, demonstrating the critical role of RA:RARγ signaling in AcH‐induced ESC differentiation.

Conclusions

ACSS2 knockouts showed no changes in differentiation phenotype, while pluripotency‐related transcripts were decreased in ALDH2 knockout ESCs. We demonstrate that AcH increases differentiation‐associated mRNAs in ESCs via RARγ.
Conditioned aversive memory associated with morphine withdrawal increases brain‐derived neurotrophic factor in dentate gyrus and basolateral amygdala
Authors: Martínez‐Laorden Elena , Navarro‐Zaragoza Javier , Milanés María‐Victoria , Laorden Maria‐Luisa , Almela Pilar
Published: July 2019

Morphine has been shown to increase the expression of brain‐derived neurotrophic factor (BDNF) in the brain. However, little is known about the effect of conditioned naloxone‐precipitated morphine withdrawal on BDNF and its precursor protein, proBDNF. We used the conditioned place aversion (CPA) paradigm to evaluate the role of corticotropin‐releasing factor (CRF)/CRF1 receptor signaling on the BDNF expression and corticosterone plasma levels after CPA expression and extinction. Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone‐associated compartment. The expression of BDNF and proBDNF in the dentate gyrus (DG) and basolateral amygdala (BLA) was measured in parallel with the corticosterone plasma levels with and without CRF1 receptor blockade. Mice subjected to conditioned naloxone‐induced morphine withdrawal showed an increased expression of BDNF (in DG and BLA) in parallel with an enhancement of corticosterone plasma levels. These results demonstrated that BDNF expression together with the increased activity of hypothalamic‐pituitary‐adrenocortical (HPA) axis are critical to the acquisition of aversive memory. However, we have observed a decrease in corticosterone plasma levels and BDNF expression after CPA extinction reaffirming the importance of BDNF in the maintenance of aversive memory. In addition, the pre‐treatment with the CRF1 receptor antagonist CP‐154 526 before naloxone conditioning session impaired morphine withdrawal‐induced aversive memory acquisition, the increased corticosterone plasma levels, and the expression of BDNF observed after CPA expression in the DG and BLA. Altogether, present results are suggesting a clear connection between HPA axis and BDNF in the formation and extinction of aversive memory.
Poverty and Divine Rewards: The Electoral Advantage of Islamist Political Parties
Authors: Grewal Sharan , Jamal Amaney A. , Masoud Tarek , Nugent Elizabeth R.
Published: July 2019

Political life in many Muslim‐majority countries has been marked by the electoral dominance of Islamist parties. Recent attempts to explain why have highlighted their material and organizational factors, such as the provision of social services. In this article, we revive an older literature that emphasizes the appeal of these parties’ religious nature to voters experiencing economic hardship. Individuals suffering economic strain may vote for Islamists because they believe this to be an intrinsically virtuous act that will be met with divine rewards in the afterlife. We explore this hypothesis through a series of laboratory experiments in Tunisia. Individuals assigned to treatment conditions instilling feelings of economic strain exhibit greater support for Islamist parties, and this support is causally mediated by an expectation of divine compensation in the hereafter. The evidence suggests that the religious nature of Islamist parties may thus be an important factor in their electoral success.
Needlescopic surgery for very low rectal cancer with no abdominal skin incision
Authors: Fukuoka Hironori , Fukunaga Yosuke , Minami Hironori , Miyanari Shun , Suzuki Shinsuke , Nagasaki Toshiya , Akiyoshi Takashi , Konishi Tsuyoshi , Fujimoto Yoshiya , Nagayama Satoshi , Ueno Masashi
Published: July 2019

Introduction

Needlescopic surgery (NS) is a minimally invasive operation beyond traditional laparoscopic surgery. This study aimed to describe NS for intersphincteric resection (ISR) and abdominoperineal resection (APR) for low rectal cancer without a small abdominal skin incision for extracting the specimen and to evaluate the safety and feasibility of the operation.

Methods

From January 2011 to April 2016, 36 patients underwent NS for either ISR or APR. By definition, NS for ISR or APR at our institution uses three 3‐mm ports and two 5‐mm ports at the umbilicus and in the right lower quadrant. The specimen was extracted through the anus or the perineal wound. The feasibility of this operation was determined based on short‐term outcomes and pathological findings.

Results

No patients required conversion to open surgery. The mean operation time was 299 minutes, and the mean estimated blood loss was 30 mL. Postoperative complications higher than Clavien–Dindo grade III occurred in 2.8% of patients (n = 1). The median number of harvested lymph nodes was 16 (range, 0‐30), and in no case was there a positive circumferential resection margin.

Conclusions

Needlescopic surgery for ISR or APR is technically safe and feasible for low rectal cancer based on the short‐term outcomes and the oncological quality, particularly when compared to conventional laparoscopic surgery as described in previous reports.
Examining the link between democracy, social policy, and inclusive development in South‐East Asia
Authors: Putra Fadillah
Published: July 2019

This research investigates the impact of democracy on inclusive development and mainly addresses the question “Does democracy matter in the delivery of larger and more effective social policies that improve inclusive development?” The four cases selected to empirically analyze the relationship among three variables (democracy, social policy, and inclusive development) were Indonesia, Malaysia, Thailand, and the Philippines. The three main variables were modeled and analyzed by partial least squares–structural equation modeling technique. The finding revealed that social policy was one of the potential variables linking democracy and inclusive development, especially when the development of democratic institution runs stably.
Enhancing wayfinding in pre‐school children through robot and socio‐cognitive conflict
Authors: Benvenuti Martina , Mazzoni Elvis
Published: July 2019

Wayfinding is one of the most important skills that children have to learn in order to safely move in the environment. One problem that 5‐year‐old children encounter with wayfinding is changing their point of view to that of another person in different position in the same environment, such as that of a person opposite them whose perspective is turned 180° with respect to their own. Robots could help children in learning this skill, since children can instruct them to move in the environment, in predetermined paths, by starting from a rotated perspective. This study compares classic socio‐cognitive conflict with a human partner, but in this case with a robot partner, in order to evaluate how a specific activity (instructing a robot to perform a given route) enhances the wayfinding skills of 156 5‐year‐old children. Using two different robots (humanoid and non‐humanoid) and two different conditions (a child and the robot and two children and the robot), the study shows that children who performed the task with the humanoid robot improved their performance significantly better compared with those who used the non‐humanoid robot. Furthermore, children engaged in the Socio‐Cognitive Conflict situation with another child‐outperformed children in the Socio‐Cognitive Conflict with robots. Finally, children with low‐level performance in the pretest made the greatest improvement both in terms of moves made and time taken to complete the task in comparison with children in the High‐Level Group and of the Control Group.
Evaluative Audience Perception (EAP): How Children Come to Care About Reputation
Authors: Botto Sara Valencia , Rochat Philippe
Published: July 2019

Despite the fact that reputational concerns are central to human psychology, we know little about when and how children come to care about the evaluation of others. In this article, we review recent studies on reputational concerns in early childhood, and propose that evaluative audience perception (EAP) is necessary to understand the developmental origins of reputation. Specifically, we argue that EAP’s two defining components—the tendency to assume that others could evaluate one’s behavior and the default preference to elicit positive instead of negative evaluations—lay the foundation for the development of reputational concerns. We provide evidence suggesting that EAP would emerge by 24 months and conclude by suggesting possible developmental models of EAP.
Emotion Reactivity and Regulation in Maltreated Children: A Meta‐Analysis
Authors: Lavi Iris , Katz Lynn Fainsilber , Ozer Emily J. , Gross James J.
Published: July 2019

The many adverse effects of child maltreatment make the scientific investigation of this phenomenon a matter of vital importance. Although the relationship between maltreatment and problematic emotion reactivity and regulation has been studied, the strength and specificity of these associations are not yet clear. We examine the magnitude of the maltreatment—child‐emotion reactivity/regulation link. Studies with substantiated maltreatment involving children aged up to 18 were included, along with a smaller number of longitudinal studies (58 papers reviewed, encompassing more than 11,900 children). In comparison to nonmaltreated children, maltreated children experience more negative emotions, behave in a manner indicative of more negative emotion, and display emotion dysregulation. We outline several theoretical implications of our results.