bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel membrane protein Hoka regulates septate junction organization and stem cell homeostasis in theDrosophilagut
Authors: Izumi Yasushi , Furuse Kyoko , Furuse Mikio
Published: November 2020

Smooth septate junctions (sSJs) regulate the paracellular transport in the intestinal and renal system in arthropods. InDrosophila, the organization and physiological function of sSJs are regulated by at least three sSJ-specific membrane proteins: Ssk, Mesh, and Tsp2A. Here, we report a novel sSJ membrane protein Hoka, which has a single membrane-spanning segment with a short extracellular region having 13-amino acids, and a cytoplasmic region with three repeats of the Tyr-Thr-Pro-Ala motif. The larval midgut inhoka-mutants shows a defect in sSJ structure. Hoka forms a complex with Ssk, Mesh, and Tsp2A and is required for the correct localization of these proteins to sSJs. Knockdown ofhokain the adult midgut leads to intestinal barrier dysfunction, stem cell overproliferation, and epithelial tumors. Inhoka-knockdown midguts, aPKC is up-regulated in the cytoplasm and the apical membrane of epithelial cells. The depletion ofaPKCandykiinhoka-knockdown midguts results in reduced stem cell overproliferation. These findings indicate that Hoka cooperates with the sSJ-proteins Ssk, Mesh, and Tsp2A to organize sSJs, and is required for maintaining intestinal stem cell homeostasis through the regulation of aPKC and Yki activities in theDrosophilamidgut.

Summary statement

Depletion ofhoka, a gene encoding a novel septate junction protein, from theDrosophilamidgut results in the disruption of septate junctions, intestinal barrier dysfunction, stem cell overproliferation, and epithelial tumors.
Biochemical and structural studies of target lectin SapL1 from the emerging opportunistic microfungusScedosporium apiospermum
Authors: Martínez-Alarcón Dania , Balloy Viviane , Bouchara Jean-Philippe , Pieters Roland J. , Varrot Annabelle
Published: November 2020

Scedosporium apiospermumis an emerging opportunistic fungal pathogen responsible for life-threatening infections in humans. Host-pathogen interactions often implicate lectins that have become therapeutic targets for the development of carbohydrate mimics for antiadhesive therapy. Here, we present the first report on the identification and characterization of a lectin fromS. apiospermumnamed SapL1. SapL1 was found using bioinformatics as a homolog to the conidial surface lectin FleA fromAspergillus fumigatusknown to play a role in the adhesion to host glycoconjugates present in human lung epithelium. In our strategy to obtain recombinant SapL1, we discovered the importance of osmolytes to achieve its expression in soluble form in bacteria. Analysis of glycan arrays indicates specificity for fucosylated oligosaccharides as expected. Submicromolar affinity was measured for fucose using isothermal titration calorimetry. We solved SapL1 crystal structure in complex with α-methyl-L-fucoside and analyzed its structural basis for fucose binding. We finally demonstrated that SapL1 binds to bronchial epithelial cells in a fucose-dependent manner. The information gathered here will contribute to the design and development of glycodrugs targeting SapL1.
The endosomal TbTpr86/TbUsp7/SkpZ (TUS) complex controls surface protein abundance in trypanosomes
Authors: Yamada Kayo , Yaqub Farzana K. , Zoltner Martin , Field Mark C.
Published: November 2020

In trypanosomes the orthologs of human USP7 and VDU1 control abundance of a cohort of surface proteins, including invariant surface glycoproteins (ISGs) by functioning as deubiquitinases (DUBs) Silencing TbUsp7 partially inhibits endocytosis and invariant surface glycoprotein turnover. As a component of cullin E3 ubiquitin ligases, S-phase kinase-associated protein 1 (Skp1) has crucial roles in cell cycle progression, transcriptional regulation, signal transduction and other processes in animals and fungi. Unexpectedly, trypanosomes possess multiple Skp1 paralogs, including a divergent paralog designated SkpZ. SkpZ is implicated in suramin-sensitivity and endocytosis and decreases in abundance following TbUsp7 knockdown and physically interacts with TbUsp7 and TbTpr86. The latter is a tetratricopeptide-repeat protein also implicated in suramin sensitivity and located close to the flagellar pocket/endosomes, consistent with a role in endocytosis. Further, silencing SkpZ reduced abundance of TbUsp7 and TbTpr86 and manytrans-membrane domain surface proteins. Our data indicate that TbTpr86, TbUsp7 andSkpZ form the ‘TUS’ complex that regulates abundance of a significant cohort of trypanosome surface proteins.
CD127 imprints functional heterogeneity to diversify monocyte responses in human inflammatory diseases
Authors: Zhang Bin , Zhang Yuan , Xiong Lei , Li Yuzhe , Zhang Yunliang , Zhao Jiuliang , Jiang Hui , Li Can , Liu Yunqi , Liu Xindong , Liu Haofei , Ping Yi-Fang , Zhang Qiangfeng Cliff , Zhang Zheng , Bian Xiu-Wu , Zhao Yan , Hu Xiaoyu
Published: November 2020

Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in patients with infectious and inflammatory conditions such as COVID-19 and rheumatoid arthritis. Multiple genomic and functional approaches revealed unique gene signatures of M127 and unified anti-inflammatory properties imposed by the CD127-STAT5 axis. M127 expansion correlated with mild COVID-19 disease outcomes. Thereby, we phenotypically and molecularly characterized a human monocyte subset marked by CD127 that retained anti-inflammatory properties within the pro-inflammatory environments, uncovering remarkable functional diversity among monocytes and signifying M127 as a potential therapeutic target for human inflammatory disorders.
Bispecific tau antibodies with additional binding to C1q or alpha-synuclein
Authors: Quint Wim Hendricus , Matečko-Burmann Irena , Schilcher Irene , Löffler Tina , Schöll Michael , Burmann Björn Marcus , Vogels Thomas
Published: November 2020

Background

Alzheimer’s disease (AD) and other tauopathies are neurodegenerative disorders characterized by cellular accumulation of aggregated tau protein. Tau pathology within these disorders is accompanied by chronic neuroinflammation, such as activation of the classical complement pathway by complement initiation factor C1q. Additionally, about half of the AD cases present with inclusions composed of aggregated alpha-synuclein called Lewy bodies. Lewy bodies in disorders such as Parkinson’s disease and Lewy body dementia also frequently occur together with tau pathology. Immunotherapy is currently the most promising treatment strategy for tauopathies. However, the presence of multiple pathological processes within tauopathies makes it desirable to simultaneously target more than one disease pathway.

Methods

Herein, we have developed three bispecific antibodies based on published antibody binding region sequences. One bispecific antibody binds to tau plus alpha-synuclein and two bispecific antibodies bind to tau plus C1q.

Results

The affinity of the bispecific antibodies to their targets compared to their monospecific counterparts ranged from nearly identical to one order of magnitude lower. All bispecific antibodies retained binding to aggregated protein in patient-derived brain sections. The bispecific antibodies also retained their ability to inhibit aggregation of recombinant tau, regardless of whether the tau binding sites were in IgG or scFv format. Mono- and bispecific antibodies inhibited cellular seeding induced by AD-derived pathological tau with similar efficacy. Finally, both Tau-C1q bispecific antibodies completely inhibited the classical complement pathway.

Conclusion

Bispecific antibodies that bind to multiple pathological targets may therefore present a promising approach to treat tauopathies and other neurodegenerative disorders.
Neural representation of words within phrases: Temporal evolution of color-adjectives and object-nouns during simple composition
Authors: Honari-Jahromi Maryam , Chouinard Brea , Blanco-Elorrieta Esti , Pylkkänen Liina , Fyshe Alona
Published: November 2020

In language, stored representations of lexical items combine into an infinitude of complex expressions. While the neuroscience of composition has begun to mature, we do not yet understand how the stored representations evolve and morph during composition. New decoding techniques allow us to crack open this very hard question: we can train a model to recognize a representation in one context or time-point and assess its accuracy in another. We combined the decoding approach with magnetoencephalography recorded during a picture naming task to investigate the temporal evolution of noun and adjective representations during speech planning. We tracked word representations as they combined into simple two-word phrases, using single words and two-word lists as non-combinatory controls. We found that nouns were generally more decodable than adjectives, suggesting that noun representations were stronger and/or more consistent across trials than those of adjectives. When training and testing across contexts and times, the representations of isolated nouns were recoverable when those nouns were embedded in phrases, but not so if they were embedded in lists. Adjective representations did not show a similar consistency across isolated and phrasal contexts. Noun representations in phrases also sustained over time in a way that was not observed for any other pairing of word class and context. These findings offer a new window into the temporal evolution and context sensitivity of word representations during composition, revealing a clear asymmetry between adjectives and nouns. The impact of phrasal contexts on the decodability of nouns may be due to the nouns’ status as head of phrase—an intriguing hypothesis for future research.
Bi-level positive airway pressure (biPAP) for non-invasive respiratory support of foals
Authors: Raidal Sharanne L , Burgmeestre Lexi , Catanchin Chee Sum Melanie , Quinn Chris T
Published: November 2020

Respiratory insufficiency and pulmonary health are important considerations in equine neonatal care, as the majority of foals are bred for athletic function. The administration of supplementary oxygen is readily implemented in equine practice settings, but this does not address respiratory insufficiency due to inadequate ventilation and is no longer considered optimal care for hypoxia in some settings. Non-invasive ventilatory strategies including continuous or bi-level positive airway pressure are effective in human and veterinary studies, and may offer improved respiratory support in equine clinical practice. The current study was conducted in two parts to investigate the use of a commercial bilevel positive airway pressure (biPAP) ventilator, designed for home care of people with obstructive respiratory conditions, for respiratory support of foals. In Part 1 a prospective observational study was conducted to evaluate the effect of sequential application of supplementary oxygen and then biPAP for respiratory support of five foals ≤ 4 days of age hospitalised with respiratory in sufficiency (Group 1) and four healthy, sedated foals < 28 days of age (Group 2). In Part 2, biPAP and supplementary oxygen were administered to six healthy foals with pharmacologically induced respiratory insufficiency in a two sequence, two phase, cross-over study (Group 3). Non-invasive ventilation by biPAP improved gas exchange and mechanics of breathing (increased tidal volume, decreased respiratory rate and increased peak inspiratory flow) in foals, but modest hypercapnia was observed in healthy, sedated foals (Groups 2 and 3). Clinical cases (Group 1) appeared less likely to develop hypercapnia in response to treatment, however the response in individual foals was variable, and close monitoring is necessary. Clinical observations, pulse oximetry and CO2monitoring of expired gases were of limited benefit in identification of foals responding inappropriately to biPAP, and improved methods to assess and monitor respiratory function are required in foals.
Coinfection ofStreptococcus pneumoniaereduces airborne transmission of influenza virus
Authors: Brown Karina Mueller , Sage Valerie Le , French Andrea J. , Jones Jennifer E. , Padovani Gabriella H. , Avery Annika J. , Myerburg Michael M. , Schultz-Cherry Stacey , Rosch Jason W. , Hiller N. Luisa , Lakdawala Seema S.
Published: November 2020

Secondary bacterial infection, especially withStreptococcus pneumoniae(Spn), is a common complication in fatal and ICU cases of influenza virus infection. During the H1N1 pandemic of 2009 (H1N1pdm09), there was higher mortality in healthy young adults due to secondary bacterial pneumonia, with Spn being the most frequent bacterial species. Previous studies in mice and ferrets have suggested a synergistic relationship between Spn and influenza viruses. In this study, we used the ferret model to study whether airborne transmission of H1N1pdm09 was influenced by coinfection with two Spn serotypes: type 2 (D39) and type 19F (BHN97). We found that coinfected animals experienced more severe clinical symptoms as well as increased bacterial colonization of the upper respiratory tract. In contrast, we observed that coinfection resulted in reduced airborne transmission of influenza virus. Only 1/3 animals coinfected with D39 transmitted H1N1pdm09 virus to a naïve recipient compared to 3/3 transmission efficiency in animals infected with influenza virus alone. A similar trend was seen in coinfection with BHN97, suggesting that coinfection with Spn reduces influenza virus airborne transmission. The decrease in transmission does not appear to be caused by decreased stability of H1N1pdm09 in expelled droplets in the presence of Spn. Rather, coinfection resulted in decreased viral shedding in the ferret upper respiratory tract. Thus, we conclude that coinfection enhances colonization and airborne transmission of Spn but decreases replication and transmission of H1N1pdm09. Our data points to an asymmetrical relationship between these two pathogens rather than a synergistic one.

Significance

Airborne transmission of respiratory viruses is influenced by many host and environmental parameters. The complex interplay between bacterial and viral coinfections on transmission of respiratory viruses has been understudied. We demonstrate that coinfection withStreptococcus pneumoniaereduces airborne transmission of influenza A viruses by decreasing viral titers in the upper respiratory tract. Instead of implicating a synergistic relationship between bacteria and virus, our work demonstrates an asymmetric relationship where bacteria benefit from the virus but where the fitness of influenza A viruses is negatively impacted by coinfection. The implications of exploring how microbial communities can influence the fitness of pathogenic organisms is a novel avenue for transmission control of pandemic respiratory viruses.
First report ofTheileria annulatain Nigeria: findings from cattle ticks in Zamfara and Sokoto States
Authors: Mamman Adamu Haruna , Lorusso Vincenzo , Adam Babagana Mohammed , Dogo Abraham Goni , Bown Kevin J , Birtles Richard J
Published: November 2020

Background

Ticks and tick-borne pathogens (TBPs) represent a significant economic burden to cattle farming in sub-Saharan Africa including Nigeria. However, in the northern part of this country, where the largest livestock population reside, little is known about the contemporary diversity of ticks and TBPs. This area is particularly vulnerable to climate change, undergoing marked transformation of habitat and associated flora and fauna that is also likely to include ticks. This study aimed to document the occurrence of tick species and Apicomplexan TBPs in cattle from North-Western Nigeria.

Methods

In 2017, ticks were collected from cattle in Zamfara and Sokoto States and identified morphologically. Additionally, a subset of ticks were screened molecularly for the detection of Apicomplexan DNA.

Results

A total of 494 adult ticks were collected from 80 cattle in Zamfara and 65 cattle in Sokoto State. Nine tick species were encountered, including sevenHyalommaspp. (i.e.Hyalomma dromedarii, Hyalomma impeltatum, Hyalomma impressum, Hyalomma marginatum, Hyalomma rufipes, Hyalomma truncatumandHyalomma turanicum),Amblyomma variegatumandRhipicephalus(Boophilus)decoloratus. All species were present in Zamfara, whereas only five species were found in Sokoto.Hyalomma rufipeswas the most prevalent tick infesting cattle in Zamfara State (76.2%), whileH. dromedariiwas the most prevalent in Sokoto State (43.7%), confirming the widespread transfer of this species from camels onto livestock and its adaptation to cattle in the region.

Of 159 ticks screened, 2 out of 54 (3.7%) from Zamfara State and 29 out of 105 (27.6%) from Sokoto State harboured DNA ofTheileria annulata, the agent of tropical theileriosis.

Conclusions

This study confirms the presence of a broad diversity of tick species in cattle from North-Western Nigeria, providing the first locality records for Zamfara State. The occurrence ofH. turanicum, recorded for the first time in Nigeria, indicates a distribution of this tick beyond Northern Africa.

This study provides the first report forT. annulatain Nigeria. Given its enormous burden on livestock farming in North Africa and across Asia, further investigations are needed to better understand its epidemiology, vector transmission and potential clinical significance in cattle from Northern Nigeria and neighbouring Sahelian countries.
SF3B1 promotes tumor malignancy through splicing-independent activation of HIF1α
Authors: Simmler Patrik T. , Cortijo Cédric , Koch Lisa M. , Galliker Patricia , Schäfer Moritz , Angori Silvia , Bolck Hella A. , Mueller Christina , Vukolic Ana , Mirtschink Peter , Christinat Yann , Davidson Natalie R. , Lehmann Kjong-Van , Pellegrini Giovanni , Pauli Chantal , Lenggenhager Daniela , Guccini Ilaria , Ringel Till , Hirt Christian , Rätsch Gunnar , Peter Matthias , Moch Holger , Stoffel Markus , Schwank Gerald
Published: November 2020

Mutations in the splicing factor SF3B1 are frequently occurring in various cancers and drive tumor progression through the activation of cryptic splice sites in multiple genes. Recent studies also demonstrate a positive correlation between expression levels of wildtype SF3B1 and tumor malignancy, but underlying mechanisms remain elusive. Here, we report that SF3B1 acts as an activator of HIF signaling through a splicing-independent mechanism. We demonstrate that SF3B1 forms a heterotrimer with HIF1α and HIF1β, facilitating binding of the HIF1 complex to hypoxia response elements (HREs) to activate target gene expression. We further validate the relevance of this mechanism for tumor progression. Monoallelic deletion of Sf3b1 impedes formation and progression of hypoxic pancreatic cancer via impaired HIF signaling, but is well tolerated in normoxic chromophobe renal cell carcinoma. Our work uncovers an essential role of SF3B1 in HIF1 signaling, providing a causal link between high SF3B1 expression and aggressiveness of solid tumors.
Protective efficacy of a SARS-CoV-2 DNA Vaccine in wild-type and immunosuppressed Syrian hamsters
Authors: Brocato Rebecca L. , Kwilas Steven A. , Kim Robert K. , Zeng Xiankun , Principe Lucia M. , Smith Jeffrey M. , Hooper Jay W.
Published: November 2020

A worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages of research and development, including several vaccines in phase 1, 2 and 3 clinical trials. A relatively small number of these vaccines have been evaluated in SARS-CoV-2 disease models, and fewer in a severe disease model. Here, a SARS-CoV-2 DNA targeting the spike protein and delivered by jet injection, nCoV-S(JET), elicited neutralizing antibodies in hamsters and was protective in both wild-type and transiently immunosuppressed hamster models. This study highlights the DNA vaccine, nCoV-S(JET), we developed has a great potential to move to next stage of preclinical studies, and it also demonstrates that the transiently-immunosuppressed Syrian hamsters, which recapitulate severe and prolonged COVID-19 disease, can be used for preclinical evaluation of the protective efficacy of spike-based COVID-19 vaccine.
The embryonic node functions as an instructive stem cell niche
Authors: Solovieva Tatiana , Lu Hui-Chun , Moverley Adam , Plachta Nicolas , Stern Claudio D.
Published: November 2020

In warm-blooded vertebrate embryos (mammals and birds), the body forms from a growth zone at the tail end. Hensen’s node, a region which induces and patterns the neural axis is located within this growth zone. The node also contains the precursors of neural, mesodermal and endodermal structures along the midline and has been suggested to contain a small population of resident stem cells. However, it is unknown whether the rest of the node constitutes an instructive stem cell niche, specifying stem cell behaviour. Here we combine transplantation of a single cell in vivo with single-cell mRNA sequencing in the chick and show that when made to enter the node, non-node-progenitor cells become resident and gain stem cell behaviour. These cells preferentially express G2/M phase cell-cycle related genes and are concentrated in posterior sub-regions of the node. The posterior part of the node therefore behaves as an instructive stem cell niche. These results demonstrate a new function for the vertebrate node during development.
Hodgkin and Huxley Opsin Model for Computationally Efficient Optogenetic Neurostimulation in Cells and Networks
Authors: Schoeters Ruben , Tarnaud Thomas , Martens Luc , Joseph Wout , Raedt Robrecht , Tanghe Emmeric
Published: November 2020

Optogenetics has a lot of potential to become an effective neuromodulative therapy for clinical application. Selecting the correct opsin is crucial to have an optimal optogenetic tool. With computational modeling, the neuronal response to the current dynamics of an opsin can be extensively and systematically tested. Unlike electrical stimulation where the effect is directly defined by the applied field, the stimulation in optogenetics is indirect, depending on the selected opsin’s non-linear kinetics. With the continuous expansion of opsin possibilities, computational studies are difficult due to the need for an accurate model of the selected opsin first. To this end, we propose a Hodgkin-and-Huxley based model (22HH) as alternative to the conventional three and four state Markov models used for opsin modeling. Furthermore, we provide a fitting procedure, which allows for nearly automatic model fitting starting from a vast parameter space. With this procedure, we successfully fitted two distinctive opsins ChR2(H134R) and MerMAID. Both models are able to represent the experimental data with great accuracy and were obtained within an acceptable time frame. This is due to the absence of differential equations in the fitting procedure, with an enormous reduction in computational cost as result. The performance of the proposed model with a fit to ChR2(H134R) was tested, by comparing the neural response in a regular spiking neuron to the response obtained with the non-instantaneous, four state Markov model (4SB), derived by Williams et al. (2013) [1]. Finally, a computational speed gain was observed with the 22HH model in a regular spiking and sparse Pyramidal-Interneuron-Network-Gamma (sPING) network simulation with respect to the 4SB-model, due to the former having two differential equations less. Consequently, the proposed model allows for computationally efficient optogenetic neurostimulation and with the proposed fitting procedure will be valuable for further research in the field of optogenetics.
The Autism Risk Factor CHD8 Is a Chromatin Activator in Human Neurons and Functionally Dependent on the ERK-MAPK Pathway Effector ELK1
Authors: Derafshi Bahareh Haddad , Danko Tamas , Chanda Soham , Batista Pedro , Litzenburger Ulrike , Lee Qian Yi , Ng Yi Han , Sebin Anu , Chang Howard Y. , Südhof Thomas C. , Wernig Marius
Published: November 2020

The chromodomain helicase DNA-binding protein CHD8 is among the most frequently found de-novo mutations in autism spectrum disorder (ASD)1–4. Despite its prominent disease involvement, little is known about its molecular function in the human brain. CHD8 is believed to be a chromatin regulator, but mechanisms for its genomic targeting is also unclear. To elucidate the role of CHD8 in human neurons, we generated conditional loss-of-function alleles in pluripotent stem cells. Chromatin accessibility and transcriptional profiling showed thatCHD8is a potent chromatin opener and transcriptional activator of its direct neuronal targets, including a distinct group of ASD genes. We found the chromatin targeting of CHD8 to be highly context-dependent. In human neurons, CHD8 was preferentially bound at promoter sequences which were significantly enriched in ETS motifs. Indeed, the chromatin state of ETS motif-containing promoters was preferentially affected upon loss of CHD8. Among the many ETS transcription factors, we found ELK1 to be the best correlated with CHD8 expression in primary human fetal and adult cortical neurons and most highly expressed in our ES cell-derived neurons. Remarkably, ELK1 was necessary to recruit CHD8 specifically to ETS motifcontaining sites. These findings imply the functional cooperativity between ELK1, a key downstream factor of the MAPK/ERK pathway, and CHD8 on chromatin involvement in human neurons. THEREFORE, the MAPK/ERK/ELK1 axis may also play a role in the pathogenesis caused byCHD8mutations5.
Diagnostic and Therapeutic Microbial Circuit with Application to Intestinal Inflammation
Authors: Merk Liana N. , Shur Andrey S. , Jena Smrutiti , Munoz Javier , Brubaker Douglas K. , Murray Richard M. , Green Leopold N.
Published: November 2020

Bacteria genetically engineered to execute defined therapeutic and diagnostic functions in physiological settings can be applied to colonize the human microbiome, providingin situsurveillance and conditional disease modulation. However, many engineered microbes can only respond to single-input environmental factors, limiting their tunability, precision, and effectiveness as living diagnostic and therapeutic systems. For engineering microbes to improve complex chronic disorders such as inflammatory bowel disease, the bacteria must respond to combinations of stimuli in the proper context and time. This work implements a previously characterized split activator AND logic gate in the probioticEscherichia colistrain Nissle 1917. Our system can respond to two input signals: the inflammatory biomarker tetrathionate and a second input signal, anhydrotetracycline (aTc), for manual control. We report 4-6 fold induction with a minimal leak when the two chemical signals are present. We model the AND gate dynamics using chemical reaction networks and tune parametersin silicoto identify critical perturbations that affect our circuit’s selectivity. Finally, we engineer the optimized AND gate to secrete a therapeutic anti-inflammatory cytokine IL-22 using the hemolysin secretion pathway in the probioticE. colistrain. We used a germ-free transwell model of the human gut epithelium to show that our engineering bacteria produce similar host cytokine responses compared to pure cytokine. Our study presents a scalable workflow to engineer cytokine-secreting microbes. It demonstrates the feasibility of IL-22 derived from probioticE. coliNissle with minimal off-target effects in a gut epithelial context.
Spaceflight Affects Neuronal Morphology and Alters Transcellular Degradation of Neuronal Debris in AdultCaenorhabditis elegans
Authors: Laranjeiro Ricardo , Harinath Girish , Pollard Amelia K. , Gaffney Christopher J. , Deane Colleen S. , Vanapalli Siva A. , Etheridge Timothy , Szewczyk Nathaniel J. , Driscoll Monica
Published: November 2020

Extended space travel, such as crewed missions to Mars and beyond, is a goal for both government space agencies and private companies. Research over the past decades, however, has shown that spaceflight poses risks to human health, including negative effects on musculoskeletal, cardiovascular, and immune systems. Details regarding effects on the nervous system have been less well described. The use of animal models holds great potential to identify and dissect conserved mechanisms of neuronal response to spaceflight. Here, we exploited the unique experimental advantages of the nematodeCaenorhabditis elegansto explore how spaceflight affects adult neuronsin vivo, at the single-cell level. We found that animals that lived 5 days of their adult life on the International Space Station exhibited considerable dendritic remodeling of the highly branched PVD neuron and modest morphological changes in touch receptor neurons when compared to ground control animals. Our results indicate hyperbranching as a common response of adult neurons to spaceflight. We also found that, in the presence of a neuronal proteotoxic stress, spaceflight promotes a remarkable accumulation of neuronal-derived waste in the surrounding tissues (especially hypodermis), suggesting an impaired transcellular degradation of debris that is released from neurons. Overall, our data reveal that spaceflight can significantly affect adult neuronal morphology and clearance of neuronal trash, highlighting the need to carefully assess the risks of long-duration spaceflight on the nervous system and to develop countermeasures to protect human health during space exploration.
Complex imaging of phase domains by deep neural networks
Authors: Wu Longlong , Juhas Pavol , Yoo Shinjae , Robinson Ian
Published: November 2020

The reconstruction of a single-particle image from the modulus of its Fourier transform, by phase-retrieval methods, has been extensively applied in X-ray structural science. Particularly for strong-phase objects, such as the phase domains found inside crystals by Bragg coherent diffraction imaging (BCDI), conventional iteration methods are time consuming and sensitive to their initial guess because of their iterative nature. Here, a deep-neural-network model is presented which gives a fast and accurate estimate of the complex single-particle image in the form of a universal approximator learned from synthetic data. A way to combine the deep-neural-network model with conventional iterative methods is then presented to refine the accuracy of the reconstructed results from the proposed deep-neural-network model. Improved convergence is also demonstrated with experimental BCDI data.
An invisible problem: stigma and FASD diagnosis in the health and justice professions
Authors: Dunbar Winsor Katharine
Published: November 2020

Purpose

Fetal alcohol spectrum disorder (FASD) is a complex lifelong disorder impacting the brain and body. Individuals with FASD may require lifelong supports and are at a higher risk of experiencing adverse outcomes, including incarceration. Individuals with FASD face stigma related to FASD that impacts disclosure of the diagnosis and access to supports. The prevalence of FASD exceeds that of other developmental disabilities, yet it remains less visible and stigmatized.

Design/methodology/approach

Interviews conducted with health-care and justice professionals in a Canadian province explore their experiences attending to FASD and challenges of stigma.

Findings

While difficult to access, diagnosis provides a pathway to supports and is crucial in the criminal justice process. Visibility and invisibility in health and justice systems highlight the lack of understanding of FASD and surrounding stigma. When unaddressed, individuals with FASD face additional challenges stemming from a lack of information and strategies by professionals involved in their lives.

Originality/value

Stigma represents a significant and complex issue intertwined in understandings of FASD. This research explores this relationship and the mechanisms through which FASD stigma has impacts in health-care and justice settings.
Circular start-up development: the case of positive impact entrepreneurship in Poland
Authors: Rok Boleslaw , Kulik Monika
Published: November 2020

Purpose

The purpose of this paper is to explore how circular start-ups design and implement innovation into their business models to increase their positive impact.

Design/methodology/approach

This qualitative study is based on an exploratory multiple-case study involving six circular start-ups with positive impact in Poland. Data gathering took place via in-depth interviews with start-up founders.

Findings

The analysis demonstrates that three factors, which are strongly interconnected, can significantly influence the development of a circular start-up. The first is the purpose-led motivation for circularity as a solution, mostly concentrated on the environmental education of different market actors. The second factor is built on the aim to increase the positive impact by addressing the most pressing social and environmental problems. It determines the impact on society as well as on the environment and the extent to which its model can be scaled up. The third factor is driven by the understanding of the purpose of the innovation, concentrated on the business model innovation regarding circularity.

Practical implications

This paper demonstrates the benefits for diverse stakeholders and the importance of using circular business models in start-up development. Circularity can be perceived as a main part of the new approach to improve sustainability.

Originality/value

Circular start-ups represent a new phenomenon in the entrepreneurial market. While the structure and logic of the circular business model in start-ups are significantly unexplored in the management literature, this model is viewed as a crucial step in the direction of increasing the positive impact of start-ups. From a theoretical and practical perspective, it is important to understand the differences and similarities in this area within different markets.
Impact on staff of the Mentally Healthy Schools Framework
Authors: Anwar-McHenry Julia , Drane Catherine F. , Joyce Phoebe , Donovan Robert J.
Published: November 2020

Purpose

The Mentally Healthy Schools Framework (MHSF), based on the population-wide Act-Belong-Commit mental health promotion campaign, is a whole-school approach primarily targeting student mental health, but it is also intended for staff. This paper presents the results of an impact survey on staff after the implementation of the Framework in a number of schools in Western Australia.

Design/methodology/approach

A baseline questionnaire was completed by n = 87 staff at schools that had just signed up to the programme, and a participant questionnaire was completed by n = 146 staff at schools that had been participating for at least 17 months.

Findings

The results show that the Framework has had a substantial impact on many staff in terms of increased mental health literacy and taking action to improve their mental health.

Originality/value

Mental health interventions in schools generally focus on students' well-being and how to deal with student mental health problems. There are few comprehensive interventions that also include staff well-being.
Approximate analytical analysis of longitudinal natural frequencies of a cracked beam
Authors: Ayas Hillal , Amara Lyes , Chabaat Mohamed
Published: November 2020

Purpose

In this paper, an approximate analytical approach is developed for the determination of natural longitudinal frequencies of a cantilever-cracked beam based on the Lagrange inversion theorem.

Design/methodology/approach

The crack is modeled by an equivalent axial spring with stiffness according to Castigliano's theorem. Thus, an implicit frequency equation corresponding to cantilever-cracked bar is obtained. The resulting equation is solved using the Lagrange inversion theorem.

Findings

Effect of different crack depths and crack positions on natural frequencies of the cracked beam is analyzed. It is shown that an increase in the crack depth ratio produces a decrease in the fundamental longitudinal natural frequency of a cracked bar. Furthermore, approximate analytical results are compared with those obtained numerically as well as from experimental tests.

Originality/value

A new approximate analytical expression of a fundamental longitudinal frequency, as a function of crack depth and crack location, is obtained.
The resilience of African migrant entrepreneurs in China under COVID-19
Authors: Prah David , Sibiri Hagan
Published: November 2020

Purpose

As the impact of COVID-19 on businesses was impossible to predict, so is the future of migrant entrepreneurs – some of whom, before the outbreak, had to deal with immigrant status associated challenges. Against this backdrop, this paper aims to focus on African migrant entrepreneurs in China, much less studied ethnic migrants who have always lived on the margins of Chinese society, to examine their entrepreneurial resilience under COVID-19 in China.

Design/methodology/approach

The study used a qualitative design using a survey and semi-structured follow-up interviews as the primary data collection instrument. The questions in the questionnaire guide were adapted from the Center for Global Development survey instrument designed to gauge the resilience of SMEs under COVID-19.

Findings

Although most business operations in China are impacted, African migrant businesses were very hit due to existing social challenges coupled with their informality (i.e. operating at a low level of organization), lack of contingency plans and lack of stimulus support. COVID-19 is thus not only a force majeure that threatens the growth expectation of African owned-business but also presents a threat to their very existence in an already challenging society for Africans.

Research limitations/implications

Although the study has achieved its intended purpose, the sample was relatively small due to the low return rate of questionnaires and the difficulties in reaching out to target respondents due to the restrictive measures on movements during the data collection period.

Originality/value

This paper draws attention to the entrepreneurship-related challenges faced by ethnic migrants in China during a crisis. The social challenges of Africans living in China became a global topical issue during the COVID-19 outbreak in China. However, little is known about their entrepreneurship endeavors and the associated difficulties. This paper helps our understanding of African businesses’ resilience in China during uncertain times, such as the one created by COVID-19.
Gender diversity and financial performance of Islamic banks
Authors: Jabari Huthayfa Nabeel , Muhamad Rusnah
Published: November 2020

Purpose

The purpose of this paper is to examine the influence of gender diversity among the board of directors (BOD) and Shariah supervisory board (SSB) members on the financial performance of Islamic banks in Indonesia and Malaysia.

Design/methodology/approach

Data for a sample of 19 Islamic banks for the period 2010–2018 were collected to test the research hypotheses using pooled ordinary least squares estimation method. Generalized least squares estimation method was used to confirm that the results are robust. This study lagged the explanatory variables by one period to control for potential endogeneity.

Findings

The findings suggest that Islamic banks with more gender-diverse BOD and SSB are expected to have better financial performance. In addition, this paper finds that an increase in Islamic banks’ size may undermine the positive impact of gender diversity among SSB members on Islamic banks’ financial performance.

Research limitations/implications

This study was conducted only on Islamic banks in Indonesia and Malaysia owing to data constraints; thus, the results may not be generalizable to Islamic banks in other countries.

Practical implications

Improving financial performance is crucial for banks, especially for Islamic banks, to sustain their fast-growing share globally. Therefore, the findings of this study are expected to provide insight and understanding in the selection and appointment of BOD and SSB members at Islamic banks.

Social implications

By having women represented in the BOD and SSB, Islamic banks will benefit equally from valuable abilities across demographic groups in the society. Furthermore, if the members of the BOD and SSB are properly selected, Islamic banks with more gender-diverse boards can effectively contribute to enhancing social welfare of various segments in the society.

Originality/value

This is the first study, as far as is known to the authors, that provides empirical evidence on the influence of gender diversity among BOD and SSB members on the financial performance of Islamic banks. This paper is expected to be used as a reference by the shareholders and customers of Islamic banks in ensuring that the BOD and SSB have the best optimal composition that maximizes their profits.
Effects of focus versus diversification on bank risk and return: evidence from Islamic banks’ loan portfolios
Authors: Al-kayed Lama Tarek , Aliani Khaoula Chaffai
Published: November 2020

Purpose

The purpose of this paper is to investigate the effect of a focus loan strategy on Islamic banks’ (IB) performance in three areas: sectoral, geographic and the type of Islamic instrument. This paper specifically addresses two questions. First, should IBs focus or diversify their loan portfolios? Second, how does focus in lending affect IBs’ returns and risk?

Design/methodology/approach

The panel generalized linear squared method was used for regressions throughout the paper. Data used in the analysis were extracted from IBs’ publicly available regulatory reports in the Gulf Cooperation Council countries. The sample is an unbalanced panel that includes financial data on 26 banks during the period 2010–2018.

Findings

Focusing on Islamic instruments and economic sectors would harm IBs’ profitability while reducing their risks. Geographic focus increased the profitability of IBs, but it also increased their default risk. The focus in Islamic instruments was beneficial when risk is low to moderate, but when the risk of an IB increased, it was better to diversify across Islamic instruments. Focus in geographical areas, on the other hand, had a non-linear U-shaped relationship with return, which means that when IBs’ risk is high, focusing their loans in one geographic area enhances their returns.

Originality/value

This paper fills the existing gap in Islamic banking literature regarding the focus/diversification dilemma. It is the first attempt to study the effect of focus in three areas (sectoral, geographic and instrument used) on the return and risk of IBs.
Intellectual capital for recovering patient centrality and ensuring patient satisfaction in healthcare sector
Authors: Fiano Fabio , Sorrentino Marco , Caputo Francesco , Smarra Margherita
Published: November 2020

Purpose

With the aim to enrich the ongoing debate about healthcare management, the paper has a twofold intent: [1] to emphasise the interpretative contribution that intellectual capital can provide to a better understanding of the relevant role of patients in the healthcare sector and [2] to investigate the relationships between the three main dimensions of intellectual capital – human capital, relational capital and structural capital – and patient satisfaction in the healthcare sector.

Design/methodology/approach

The intellectual capital framework is contextualised in the healthcare sector, and the relationships among patient evaluations of human capital, relational capital and structural capital and patient satisfaction are tested via structural equation modelling (SEM) using primary data collected with reference to a sample of 561 Italian patients involved in post survey treatments in three Italian hospitals.

Findings

The role of intellectual capital in supporting a better understanding of processes and dynamics of patient satisfaction in the healthcare sector is underlined. The empirical research provides possible guidelines for recovery patients centrality in healthcare management.

Originality/value

The paper shows how an intellectual capital framework can support a better understanding and management of dynamics and processes through which patient centrality and satisfaction in healthcare management can be enforced.
A strange situation indeed: Fostering leader–follower attachment security during unprecedented crisis
Authors: Hinojosa Amanda S. , Shaine Megan J. Doughty , McCauley Kelly Davis
Published: November 2020

Purpose

We discuss how attachment theory can help leaders maintain security in their relationships with followers during crisis, using the COVID-19 worldwide pandemic as an example. We describe how the COVID-19 pandemic has undermined the typical ways leaders may have fostered secure relationships with their followers. Guided by Lewin's action research paradigm, we integrate research on attachment theory with recent research on the COVID-19 pandemic to present leader interventions to maintain attachment security in spite of the disruption caused by COVID-19. We then discuss how these propositions can guide leader interventions in other types of crisis.

Design/methodology/approach

Attachment theory has received considerable attention in recent years from management and leadership scholars. We extend this line of inquiry by drawing parallels between the strange situation, a now classic paradigm for researching infant–caregiver attachment systems, to understand attachment security in leader–follower relationships during times of crisis.

Findings

We find that the crises such as COVID-19 present a challenge to attachment security in leader–follower relationships. We also find that research on adult attachment in response to crises and traumatic events is relevant to understanding how leaders can foster positive relations with followers during times of crisis when physical proximity is not possible.

Originality/value

We apply attachment theory and leadership research to present a framework for leadership during the COVID-19 pandemic; however, many of our theoretical assertions and related interventions could be applied to other unprecedented crises that disrupt leader–follower relationships. Hence, our paper offers a unique lens that is centered on the attachment security within the leader–follower relationship during crisis.