bluuebunny/crossref_metadata_2025 huggingface dataset:
Mussel memory: bivalves learn to fear parasites
Authors: Selbach Christian , Marchant Loïc , Mouritsen Kim N.
Published: August 2021

Fear plays a crucial role in predator-prey interactions and can have cascading impacts on the structure of whole ecosystems. Comparable fear effects have recently been described for hosts and their parasites but our understanding of the underlying mechanisms remains limited by the lack of empirical examples. Here, we experimentally tested if bivalvesMytilus eduliscan ‘learn to fear’ the infective transmission stages (cercariae) of the trematodeHimasthla elongataand if experienced mussels change their parasite-avoidance behaviour accordingly. Our results show that previous experience with parasites, but not infection per se, lead to a reduced filtration activity in mussels in the presence of cercariae compared to parasite-naïve conspecifics. This reduction in filtration activity resulted in lower infection rates in mussels. Since parasite avoidance comes at the cost of lower feeding rates, mussels likely benefit from the ability to adjust their defence behaviour when infection risks are high. Overall, these dynamic learning processes of avoidance behaviour can be expected to play a significant role in regulating the bivalves’ ecosystem engineering function in coastal habitats.
Spatio-temporal feature based deep neural network for cell lineage analysis in microscopy images
Authors: Chen Siteng , Paek Andrew L. , Lasick Kathleen A. , Loganathan Suvithanandhini , Roveda Janet , Li Ao
Published: August 2021

Background

Time-lapse microscopy has been widely used in biomedical experiments because it can visualize the molecular activities of living cells in real time. However, biomedical researchers are still conducting cell lineage analysis manually. Developing automatic lineage tracing algorithms is a challenging task. In the past two decades, deep neural networks (DNNs) became have shown outstanding performance on computer vision tasks. They can learn complex visual features, capture long-range temporal dependencies, and have the potential to be used for automatic cell lineage analysis.

Methods

In this study, we propose a multi-task spatio-temporal feature based deep neural network for cell lineages analysis (Cell-STN). The Cell-STN extracts spatio-temporal features from microscopy image sequences by leveraging our convolutional long short-term memory based core block. And the proposed Cell-STN utilized a task specific network to predict the cell location, the mitosis event, and the apoptosis event in a multi-task manner.

Results

We evaluated the Cell-STN on three in-house datasets (MCF7, U2OS, and HCT116) and one public dataset (Fluo-N2DL-HeLa). For cell tracking, we used peak-wise precision, track-wise precision, end-peak precision, and spatial distance as metrics. The overall results showed the Cell-STN models outperform other state-of-the-art cell trackers. For mitosis and apoptosis tasks, we used accuracy, F1-score, temporal distance, and spatial distance as metrics. The Cell-STN models achieved the highest performance on all datasets.

Conclusion

This study presented a novel DNNs approach for cell lineage analysis in microscopy images. The Cell-STN showed outstanding performance on the four datasets. Additionally, the Cell-STN required minimal training data and can be adapted to new biological event detection tasks by appending task-specific layers. This algorithm has the potential to be used in real-world biomedical research.
Validation and invalidation of SARS-CoV-2 main protease inhibitors using the Flip-GFP and Protease-Glo luciferase assays
Authors: Ma Chunlong , Tan Haozhou , Choza Juliana , Wang Yuying , Wang Jun
Published: August 2021

SARS-CoV-2 main protease (Mpro) is one of the most extensive exploited drug targets for COVID-19. Structurally disparate compounds have been reported as Mproinhibitors, raising the question of their target specificity. To elucidate the target specificity and the cellular target engagement of the claimed Mproinhibitors, we systematically characterize their mechanism of action using the cell-free FRET assay, the thermal shift-binding assay, the cell lysate Protease-Glo luciferase assay, and the cell-based Flip-GFP assay. Collectively, our results have shown that majority of the Mproinhibitors identified from drug repurposing including ebselen, carmofur, disulfiram, and shikonin are promiscuous cysteine inhibitors that are not specific to Mpro, while chloroquine, oxytetracycline, montelukast, candesartan, and dipyridamole do not inhibit Mproin any of the assays tested. Overall, our study highlights the need of stringent hit validation at the early stage of drug discovery.

Graphical abstract

Flip-GFP and Protease-Glo luciferase assays, coupled with the FRET and thermal shift binding assays, were applied to validate the reported SARS-CoV-2 Mproinhibitors.
Comparing the efficiency of monofilament and traditional nets for capturing bats
Authors: Chaves-Ramírez Silvia , Castillo-Salazar Christian , Sánchez-Chavarría Mariela , Solís-Hernández Hellen , Chaverri Gloriana
Published: August 2021

Traditional mist nets used for capturing bats have several drawbacks, particularly that they are inefficient at sampling many insectivorous species. One possible alternative is to use monofilament nets, whose netting is made of single strands of yarn instead of several as regular nets, making them less detectable. To date, no study has quantified the capture efficiency of monofilament nets compared to regular mist nets for the study of bats. Here we compare capture efficiency of monofilament and regular mist nets, focusing on bat abundance and species diversity at a lowland tropical forest in southwestern Costa Rica. During our sampling period, we captured 90 individuals and 14 species in regular nets and 125 individuals and 20 species in monofilament nets. The use of monofilament nets increased overall capture rates, but most notably for insectivorous species. Species accumulation curves indicate that samples based on regular nets are significantly underestimating species diversity, most notably as these nets fail at sampling rare species. We show that incorporating monofilament nets into bat studies offers an opportunity to expand records of different guilds and rare bat species and to improve our understanding of poorly-known bat assemblages while using a popular, relatively cheap and portable sampling method.
Vaccines alone are no silver bullets: a modeling study on the impact of efficient contact tracing on COVID-19 infection and transmission
Authors: Raja Dhesi Baha , Abdul Taib Nur Asheila , Teo Alvin Kuo Jing , Jayaraj Vivek Jason , Ting Choo-Yee
Published: August 2021

Background

The computer simulation presented in this study aimed to investigate the effect of contact tracing on COVID-19 transmission and infection in the context of rising vaccination rates.

Methods

This study proposed a deterministic SEIRV model with contact tracing and vaccination components. We initialized some parameters using the Malaysian COVID-19 data to inform the model. We defined contact tracing effectiveness as the proportion of contacts of a positive case that was successfully traced and vaccination rate as the proportion of daily doses administered per population in Malaysia. Sensitivity analyses on the untraced and infectious populations were conducted. The study presented in silico findings on multiple scenarios by varying the contact tracing effectiveness and daily vaccination rates.

Results

At a vaccination rate of 1.4%, a contact tracing with the effectiveness of 70% could delay the peak of untraced asymptomatic cases by 17 days and reduce the highest number of daily cases by 70% compared with a 30% contact tracing effectiveness. A similar trend was observed for symptomatic cases when a similar experiment setting was used. We also performed sensitivity analyses by using different combinations of contact tracing effectiveness and vaccination rates. In all scenarios, the effect of contact tracing on COVID-19 incidence persisted for both asymptomatic and symptomatic cases.

Conclusion

Despite testing only on two public health and social measures (PHSMs), we observed the scenario with low contact tracing and increasing vaccination rates successfully mimicked the current transmission trend in Malaysia. Hence, while vaccines are progressively rolled out, efficient contact tracing must be rapidly implemented concurrently to reach, find, test, isolate, and support the affected populations to bring the pandemic under control.
Conserved secreted effectors determine endophytic growth and multi-host plant compatibility in a vascular wilt fungus
Authors: Redkar Amey , Sabale Mugdha , Schudoma Christian , Zechmann Bernd , Gupta Yogesh K. , López-Berges Manuel S. , Venturini Giovanni , Gimenez-Ibanez Selena , Turrà David , Solano Roberto , Pietro Antonio Di
Published: August 2021

Fungal interactions with plant roots, either beneficial or detrimental, have a major impact on agriculture and ecosystems. The soil inhabiting ascomyceteFusarium oxysporum(Fo) constitutes a species complex of worldwide distribution causing vascular wilt in more than a hundred different crops. Individual isolates of the fungus exhibit host-specific pathogenicity, determined by proteinaceous effectors termed secreted in xylem (SIX). However, such isolates can also colonize roots of non-host plants asymptomatically as endophytes, or even protect them against pathogenic isolates. The molecular determinants of multi-host plant colonization are currently unknown. Here, we identified a set of fungal effectors termed ERCs (EarlyRootCompatibility effectors), which are secreted during early biotrophic growth of Fo on both host and non-host plants. In contrast to the strain-specific SIX effectors, which are encoded on accessory genomic regions, ERCs are encoded on core regions and are found across the entire Fo species complex as well as in other phytopathogens, suggesting a conserved role in fungus-plant associations. Targeted deletion of ERC genes in a pathogenic Fo isolate resulted in reduced virulence on the host plant and rapid activation of plant immune responses, while in a non-pathogenic isolate it led to impaired root colonization and loss of biocontrol ability. Strikingly, some ERCs also contribute to Fo infection on the non-vascular land plantMarchantia polymorpha. Our results reveal an evolutionarily conserved mechanism for multi-host colonization by root infecting fungi.
Unique Microglial Transcriptomic Signature within the Hippocampal Neurogenic Niche
Authors: Chintamen Sana , Gaur Pallavi , Vo Nicole , Bradshaw Elizabeth M. , Menon Vilas , Kernie Steven G.
Published: August 2021

Microglia, the resident immune cells of the brain, are crucial in the development of the nervous system. Recent evidence demonstrates that microglia modulate adult hippocampal neurogenesis by inhibiting cell proliferation of neural precursors and survival both in vitro and in vivo, thus maintaining a balance between cell division and cell death in the neural stem cell pool. There are increasing reports suggesting these microglia found in neurogenic niches differ from their counterparts in non-neurogenic areas. Here, we present evidence that microglia in the hippocampal neurogenic niche are a specialized population that express genes known to regulate neurogenesis. By comprehensively profiling myeloid lineage cells in the hippocampus using single cell RNA-sequencing, we resolve transcriptomic differences in microglia originating from the subgranular zone. These cells have lower expression of genes associated with homeostatic microglia and increased expression of genes associated with phagocytosis. Intriguingly, this small yet distinct population expresses a gene signature with substantial overlap with previously characterized phenotypes, including disease associated microglia (DAM), a particularly unique and compelling microglial state.
Unevolved proteins from modern and prebiotic amino acids manifest distinct structural profiles
Authors: Tretyachenko Vyacheslav , Vymětal Jiří , Neuwirthová Tereza , Vondrášek Jiří , Fujishima Kosuke , Hlouchová Klára
Published: August 2021

Natural proteins represent numerous but tiny structure/function islands in a vast ocean of possible protein sequences, most of which has not been explored by either biological evolution or research. Recent studies have suggested this uncharted sequence space possesses surprisingly high structural propensity, but development of an understanding of this phenomenon has been awaiting a systematic high-throughput approach.

Here, we designed, prepared, and characterized two combinatorial protein libraries consisting of randomized proteins, each 105 residues in length. The first library constructed proteins from the entire canonical alphabet of 20 amino acids. The second library used a subset of only 10 residues (A,S,D,G,L,I,P,T,E,V) that represent a consensus view of plausibly available amino acids through prebiotic chemistry. Our study shows that compact conformations resistant to proteolysis are (i) abundant (up to 40%) in random sequence space, (ii) independent of general Hsp70 chaperone system activity, and (iii) not granted solely by “late” and complex amino acid additions. The Hsp70 chaperone system effectively increases solubility and refoldability of the canonical alphabet but has only a minor impact on the “early” library. The early alphabet proteins are inherently more soluble and refoldable, possibly assisted by the cell-like environment in which these assays were performed.

Our work indicates that both early and modern amino acids are predisposed to supporting protein structure (either in forms of oligomers or globular/molten globule structures) and that protein structure may not be a unique outcome of evolution.
Cooperative Amyloid Fibre Binding and Disassembly by the Hsp70 disaggregase
Authors: Beton J. G. , Monistrol J , Wentink A , Johnston EC , Roberts AJ , Bukau B , Hoogenboom BW , Saibil HR
Published: August 2021

Although amyloid fibres are highly stable protein aggregates, a specific combination of human Hsp70 system chaperones can disassemble them, including fibres formed of α-synuclein, huntingtin or Tau. Disaggregation requires the ATPase activity of the constitutively expressed Hsp70, Hsc70, together with the J domain protein DNAJB1 and the nucleotide exchange factor Apg2. Recruitment and clustering of Hsc70 on the fibrils appear to be necessary for disassembly.

Here we use atomic force microscopy (AFM) to show that segments of in vitro assembled α-synuclein fibrils are first coated with chaperones and then undergo bursts of rapid, unidirectional disassembly. Cryo-electron tomography reveals fibrils with regions of densely bound chaperones extending from the fibre surface, preferentially at one end of the fibre. Sub-stoichiometric amounts of Apg2 relative to Hsc70 dramatically increase recruitment of Hsc70 to the fibres, creating localised active zones that then undergo rapid disassembly at a rate of ∼4 subunits per second.
Comprehensive analysis of mRNA poly(A) tail reveals complex and conserved regulation
Authors: Liu Yusheng , Nie Hu , Zhang Yiwei , Lu Falong , Wang Jiaqiang
Published: August 2021

Non-templated poly(A) tails are added to the 3′-end of most mRNAs, which have important roles in post-transcriptional regulation1–3. Recent studies have revealed that poly(A) tails are not composed purely of A residues, but also contain U, C and G residues internally and at their 3′-ends4–6, revealing new levels of complexity. However, no method is able to analyze these internal and terminal non-A residues simultaneously. Here, we developed a new method called unbiased capture of 3-terminal followed by full-length RNA sequencing (UCTF-seq) which captures RNA 3′-ends by direct 3′ adaptor ligation and rRNA removal by CRISPR/Cas9. This method allows simultaneous evaluation of the poly(A) tail length and 5′-end, internal, and 3′-end non- A residues together with the full-length cDNA for a transcript. Applying this method, we achieved the first complete transcriptome-wide 3′ tail map of mRNA within the nuclear and cytoplasmic compartments of mammalian cells, uncovering differences in poly(A) tail length and non-A residues between these two mRNA populations. A survey of diverse eukaryotic species revealed the conservation of a subset of poly(A) tails containing consecutive U residues in the internal positions, whereas those with consecutive C or G residues were of much lower abundance. Together, we established the first method to be able to comprehensively analyze poly(A) tail 5′-end, internal and 3′-end non-A residues in addition to the length simultaneously, and reveal the first complete mRNA 3′ tail map, providing rich insights into the regulatory roles of poly(A) tails.
Maternal mRNA deadenylation is defective in in vitro matured mouse and human oocytes
Authors: Liu Yusheng , Tao Wenrong , Zhang Yiwei , Nie Hu , Hou Zhenzhen , Zhang Jingye , Yang Zhen , Wang Jiaqiang , Lu Falong , Wu Keliang
Published: August 2021

Oocyte in vitro maturation is a technique of assisted reproductive technology that was first introduced in patients with polycystic ovarian syndrome and is now used in most fertility clinics. Thousands of genes show abnormally high expression in in vitro maturated metaphase II (in vitro MII) oocytes compared with in vivo maturated metaphase II (in vivo MII) oocytes in bovines, mice, and humans1-3. However, the underlying mechanisms of this abnormal expression are still poorly understood. In this study, we use PAIso-seq1 to reveal a transcriptome-wide expression profile of full-length transcripts containing entire poly(A) tails in in vivo and in vitro matured mouse and human oocytes. Our results indicate that more genes are up-regulated than down-regulated in in vitro MII oocytes in both mice and humans. Furthermore, we demonstrate that the observed increase in maternal mRNA abundance is caused by impaired deadenylation in in vitro MII oocytes in both mice and humans. We also found that the cytoplasmic polyadenylation of dormant Btg4 and Cnot7 mRNAs, which encode key components of deadenylation machinery, is impaired in in vitro MII oocytes in mice and humans respectively, likely contributing to reduced translation and impaired global maternal mRNA deadenylation. Our findings highlight that impaired maternal mRNA deadenylation is a definite molecular defect in in vitro MII oocytes in both mice and humans. The findings here offer a new criterion for evaluating the quality of in vitro MII oocytes and a potential direction for improving in vitro maturation by fixing the dysregulated maternal mRNA deadenylation.
A novel post-developmental role of the Hox genes underlies normal adult behaviour
Authors: Raouf Issa A. , Alonso Claudio R.
Published: August 2021

The molecular mechanisms underlying the stability of mature neurons and neural circuits are poorly understood. Here we explore this problem and discover that the Hox genes are a component of the genetic programme that maintains normal neural function in adult Drosophila. We show that post-developmental downregulation of the Hox gene Ultrabithorax (Ubx) in adult neurons leads to substantial anomalies in flight. Mapping the cellular basis of these effects reveals that Ubx is required within a subset of dopaminergic neurons, and cell circuitry analyses and optogenetics allow us to link these dopaminergic neurons to flight control. Functional imaging experiments show that Ubx is necessary for normal dopaminergic activity, and neuron-specific RNA-sequencing defines two previously uncharacterised ion channel-encoding genes as potential mediators of Ubx behavioural roles. Our study thus reveals a novel role of the Hox system in controlling adult behaviour and neural function.
Exo1-protected DNA nicks direct crossover formation in meiosis
Authors: Gioia Michael , Payero Lisette , Pannafino Gianno , Chen Jun Jie , Salim Sagar , Fajith Ghanim , Farnaz Amamah F. , Momoh Sherikat , Scotland Michelle , Raghavan Vandana , Manhart Carol , Shinohara Akira , Nishant K.T. , Alani Eric
Published: August 2021

In most sexually reproducing organisms crossing over between chromosome homologs during meiosis is critical for the viability of haploid gametes. Most crossovers that form in meiosis in budding yeast result from the biased resolution of double Holliday Junction (dHJ) intermediates. This dHJ resolution step involves the actions Rad2/XPG family nuclease Exo1 and the Mlh1-Mlh3 mismatch repair endonuclease. At present little is known about how these factors act in meiosis at the molecular level. Here we show that Exo1 promotes meiotic crossing over by protecting DNA nicks from ligation. We found that structural elements in Exo1 required for interactions with DNA, such as bending of DNA during nick/flap recognition, are critical for its role in crossing over. Consistent with these observations, meiotic expression of the Rad2/XPG family member Rad27 partially rescued the crossover defect inexo1null mutants, and meiotic overexpression of Cdc9 ligase specifically reduced the crossover levels ofexo1DNA binding mutants to levels approaching theexo1null. In addition, our work identified a role for Exo1 in crossover interference that appears independent of its resection activity. Together, these studies provide experimental evidence for Exo1-protected nicks being critical for the formation of meiotic crossovers and their distribution.
Adipocyte-Specific Ablation Of PU.1 Promotes Energy Expenditure and Ameliorates Metabolic Syndrome In Aging Mice
Authors: Chen Keyun , De Angulo Alejandra , Guo Xin , More Aditya , Ochsner Scott A. , Lopez Eduardo , Saul David , Pang Weijun , Sun Yuxiang , McKenna Neil J. , Tong Qiang
Published: August 2021

Objective

Although PU.1/Spi1 is known as a master regulator for macrophage development and function, we have reported previously that it is also expressed in adipocytes and is transcriptionally induced in obesity. Here, we investigated the role of adipocyte PU.1 in the development of age-associated metabolic syndrome.

Methods

We generated mice with adipocyte specific PU.1 knockout, assessed metabolic changes in young and aged PU.1fl/fl(control) and AdipoqCre PU.1fl/fl(aPU.1KO) mice, including body weight, body composition, energy expenditure and glucose homeostasis. We also performed transcriptional analyses using RNA-Sequencing of adipocytes from these mice.

Results

aPU.1KO mice have elevated energy expenditure at a young age and decreased adiposity and increased insulin sensitivity in later life. Corroborating these observations, transcriptional network analysis indicated the existence of validated, aPU.1-modulated regulatory hubs that direct inflammatory and thermogenic gene expression programs.

Conclusions

Our data provide evidence for a previously uncharacterized role of PU.1 in the development of age-associated obesity and insulin resistance.
Constructing Tumor Immune Microenvironment and Identifying the Immune-Related Prognostic Signatures in Colorectal Cancer Using Multi-omics Data
Authors: Zhang Shuai , Lv Jiali , Fan Bingbing , Fan Zhe , Li Chunxia , Gu Bingbing , Yu Wenhao , Zhang Tao
Published: August 2021

Background

The tumor immune microenvironment (TIME) plays a key role in occurrence, progression and prognosis of colorectal cancer (CRC). However, the genetic and epigenetic alterations and potential mechanisms in the TIME of CRC are still unclear.

Methods

We investigated the immune-related differences in three types of genetic or epigenetic alterations (gene expression, somatic mutation, and DNA methylation) and considered the potential roles that these alterations have in the immune response and the immune-related biological processes by analyzing the multi-omics data from The Cancer Genome Atlas (TCGA) portal. Additionally, a four-step method based on LASSO regression and Cox regression was used to construct the prognostic prediction model. Cross validation was performed to validate the model.

Results

A total of 1,745 differentially expressed genes, 178 differentially mutated genes and 1,961 differentially methylation probes were identified between the high-immunity group and the low-immunity group. We retained 15 genetic and epigenetic variables after using LASSO regression and Cox regression. For the prognostic predictions on the TCGA profiles, the performance of the model with 1-year, 3-year, and 5-year areas under the curve (AUCs) equal to 0.861, 0.797, and 0.875. Finally, the overall risk score model was constructed based on genetic, epigenetic, demographic and clinical characteristics, which comprised 18 variables and achieved a high degree of accuracy on the 1-year (AUC = 0.865), 3-year (AUC = 0.839), and 5-year (AUC = 0.914) survival predictions. Kaplan-Meier survival analysis demonstrated that the overall survival of the high-risk group was significantly poorer compared with the low-risk group. Prognostic nomogram, calibration plot and cross validation showed excellent predictive performance.

Conclusions

Our study provides a new clue to explore the TIME of CRC patients in genetic and epigenetic aspects. Meanwhile, the prognostic model also has clinical prognostic value and may provide new indicators for the treatment of CRC patients.
National Excess Mortality from Sub-National data: Method and Application for Argentina
Authors: Karlinsky Ariel
Published: August 2021

Currently, many countries have not yet reported 2020 or 2021 mortality data to allow an estimate of excess mortality during the COVID-19 pandemic. However, some countries have sub-national mortality data, at the state, province or city level. I present a simple method to allow estimation of national level mortality and excess mortality from sub-national data, using the case of Argentina and projecting excess mortality up to August 2021.
EVALUATION OF STED SUPER-RESOLUTION IMAGE QUALITY BY IMAGE CORRELATION SPECTROSCOPY (QuICS)
Authors: Cerutti Elena , D’Amico Morgana , Cainero Isotta , Dellino Gaetano Ivan , Faretta Mario , Vicidomini Giuseppe , Pelicci Pier Giuseppe , Bianchini Paolo , Diaspro Alberto , Lanzanò Luca
Published: August 2021

Quantifying the imaging performances in an unbiased way is of outmost importance in super-resolution microscopy. Here, we describe an algorithm based on image correlation spectroscopy (ICS) that can be used to assess the quality of super-resolution images. The algorithm is based on the calculation of an autocorrelation function and provides three different parameters: the width of the autocorrelation function, related to the spatial resolution; the brightness, related to the image contrast; the relative noise variance, related to the signal-to-noise ratio of the image. We use this algorithm to evaluate the quality of stimulated emission depletion (STED) images of DNA replication foci in U937 cells acquired under different imaging conditions. Increasing the STED power improves the resolution but may reduce the image contrast. Increasing the number of line averages improves the signal-to-noise ratio but facilitates the onset of photobleaching and subsequent reduction of the image contrast. Finally, we evaluate the performances of two different separation of photons by lifetime tuning (SPLIT) approaches: the method of tunable STED power and the commercially available Leica Tau-STED. We find that SPLIT provides an efficient way to improve the resolution and contrast in STED microscopy.
Nanobodies as allosteric modulators of Parkinson’s disease-associated LRRK2
Authors: Singh Ranjan K. , Soliman Ahmed , Guaitoli Giambattista , Störmer Eliza , von Zweydorf Felix , Maso Thomas Dal , Van Rillaer Laura , Schmidt Sven H. , Chatterjee Deep , Pardon Els , Knapp Stefan , Kennedy Eileen J. , Steyaert Jan , Herberg Friedrich W. , Kortholt Arjan , Gloeckner Christian J. , Versées Wim
Published: August 2021

Mutations in the gene coding for Leucine-Rich Repeat Kinase 2 (LRRK2) are a leading cause of the inherited form of Parkinson’s disease (PD), while LRRK2 overactivation is also associated with the more common idiopathic form of PD. LRRK2 is a large multi-domain protein, including a GTPase as well as a Ser/Thr protein kinase domain. Common disease-causing mutations increase LRRK2 kinase activity, presenting LRRK2 as an attractive target for inhibitory drug design. Currently, drug development has mainly focused on ATP-competitive kinase inhibitors. Here, we report the identification and characterization of a variety of Nanobodies that bind to different LRRK2 domains and inhibit or activate LRRK2 activity in cells and in vitro. Importantly, diverse groups of Nanobodies were identified that inhibit LRRK2 kinase activity through a mechanism that does not involve binding to the ATP pocket or even to the kinase domain. Moreover, while certain Nanobodies completely inhibit the LRRK2 kinase activity, we also identified Nanobodies that specifically inhibit the phosphorylation of Rab protein substrates. Finally, in contrast to current type-I kinase inhibitors, the studied kinase-inhibitory Nanobodies did not induce LRRK2 microtubule association. These comprehensively characterized Nanobodies represent versatile tools to study the LRRK2 function and mechanism, and can pave the way toward novel diagnostic and therapeutic strategies for PD.
Hybridization as practice: clinical engagement with performance metrics and accounting technologies in the English NHS
Authors: Begkos Christos , Antonopoulou Katerina
Published: August 2021

Purpose

This study aims to investigate the hybridization practices that medical managers engage with to promote accounting and performance measurement in the hybrid setting of healthcare. In doing so, the authors explore how medical managers enact and become practitioners of hybridity.

Design/methodology/approach

The authors adopt a practice lens to conceptualize hybridization as an emergent, situated practice and capture the micro-activities that medical managers engage with when they enact hybridity. The authors conducted semi-structured interviews with medical managers, business managers and coding professionals and collected documents at an English National Health Service (NHS) hospital over the course of five years.

Findings

The findings accentuate two emergent practices through which medical managers instill hybridity to individuals who are hesitant or resistant to hybridization. Medical managers engage in equivocalizing and de-stigmatizing practices to broaden the understandings, further diversify or reconcile the teleologies of clinicians in non-managerial roles. In doing so, the authors signal the merits of accounting in improving care outcomes and remove the stigma associated to clinical engagement with costs.

Originality/value

The study contributes to hybridization and practice theory literature via capturing how hybridity is enacted in practice in a healthcare setting. As medical managers engage with and promote accounting information and performance measurement technologies in their practice environment, they transcend professional boundaries and hybridize the professional spaces that surround them.
A novel retractable landing gear of a light amphibious airplane design, synthesis, analysis, and implementation
Authors: Chinvorarat Sinchai , Vallikul Pumyos
Published: August 2021

Purpose

The purpose of this paper is to present a novel retractable main landing gear for a light amphibious airplane, while the design, synthesis and analysis are given in details for constructing the main landing gear.

Design/methodology/approach

The constraint three-position synthesis has given the correct path of all linkages that suitably fit the landing gear into the compartment. The additional lock-link is introduced into the design to ensure the securement of the mechanism while landing. Having the telescopic gas-oil shock strut as a core element to absorb the impact load, it enhances the ability and efficiency to withstand higher impact than others type of light amphibious airplane.

Findings

By kinematics bifurcation analysis, the optimized value of the unlock spring stiffness at 90 N/m can be found to tremendously reduce the extended-retracted linear actuator force from 500 N to 150 N at the beginning of the retraction sequence. This could limit the size and weight of the landing gear actuator of the light amphibious airplane.

Practical implications

The drop test of the landing gear to comply with the ASTM f-2245 (Standard Specification for Design and Performance of a Light Sport Airplane) reveals that the novel landing gear can withstand the impact load at the drop height determined by the standard. The maximum impact loading 4.8 G occurs at the drop height of 300 mm, and there is no sign of any detrimental or failure of the landing gear or the structure of the light amphibious airplane. The impact settling time response reaches the 2% of steady-state value in approximately 1.2 s that ensure the safety and stability of the amphibious airplane if it subjects to an accidentally hard landing.

Originality/value

This paper presents unique applications of a retractable main landing gear of a light amphibious airplane. The proposed landing gear functions properly and complies with the drop test standard, ensuring the safety and reliability of the airplane and exploiting the airworthiness certification process.
The effect of wavy surface on boundary layer instabilities of an airfoil
Authors: Rarata Zbigniew
Published: August 2021

Purpose

The purpose of this paper is to investigate airfoil’s tonal noise reduction mechanism when deploying surface irregularities, such as surface waviness by means of spatial stability analyses.

Design/methodology/approach

Flow field calculations over smooth and wavy-surface NACA 0012 airfoils at 2° angle of attack and at Reynolds number of 200,000 are performed using the large eddy simulation (LES) approach. Three geometrical configurations are considered: a smooth NACA 0012 airfoil, wavy surface on the suction side (SS) and wavy surface on the pressure side (PS). The spatial stability analyses using the LES-generated flow fields are conducted and validated against the Orr-Sommerfeld stability analysis for the smooth airfoil configuration.

Findings

The spatial stability analyses show that inclusion of the wavy-type modification on the SS of the airfoil does not lead to altering of the acoustic feedback loop mechanism, with respect to the mechanism observed for the smooth airfoil configuration. In contrast, applying the surface modifications to the airfoil PS leads to a significant reduction of the amplification range of disturbances in the vicinity of the trailing edge for the frequency of the acoustic feedback loop mechanism.

Practical implications

The spatial analyses using, for example, LES-generated flow fields can be widely used to determine acoustic sources and associated distributions of amplifications for a wide range of applications in the aeroacoustics.

Originality/value

The spatial stability analysis approach based on flow fields computed a priori using the LES method has been introduced, validated and used to determine behaviour of the acoustic feedback loop when accurate reconstruction of geometry effects is required.
Factors affecting adoption of digital payments by semi-rural Indian women: extension of UTAUT-2 with self-determination theory and perceived credibility
Authors: Manrai Rishi , Goel Utkarsh , Yadav Prashant Dev
Published: August 2021

Purpose

The aim of this research is to investigate the factors influencing the adoption of digital payments by the semi-rural women in India.

Design/methodology/approach

The study extended the factors of unified theory of acceptance and use of technology UTAUT-2, with perceived credibility and self-determination theory to understand the use behaviour of the rural Indian women. The study checked the mediating role of some constructs besides testing the direct relationship. The study was conducted in the rural parts of the adjoining areas of Delhi, where the women from different states, education and financial background live. The research model was empirically tested on 568 respondents using structural equation modelling (SEM) technique.

Findings

The research model was able to explain 72.6% variance in the user behaviour variable. Effort expectancy, habit, facilitating conditions as well as perceived competence emerged out to be significant determinants of use behaviour. Besides these direct relationships, two constructs, habit as well as facilitating conditions were found to partially mediate the relationship between behavioural intention and behaviour.

Originality/value

This study provides some very critical clues for the companies providing digital payment services, by highlighting the significant factors explaining the technology adoption by semi-rural women. The companies must devise suitable marketing strategies to inculcate trust in mind of perspective customers towards their companies as well as the service provided by them. The role of simple digital platform, that is easy to learn and use, is also an important element in determining the technology adoption.
Street food handlers' food safety knowledge, attitudes and self-reported practices and consumers' perceptions about street food vending in Maseru, Lesotho
Authors: Letuka Ponts'o , Nkhebenyane Jane , Thekisoe Oriel
Published: August 2021

Purpose

Food safety knowledge and hygienic practices by food handlers play an important role in the prevention of contamination of food prepared.

Design/methodology/approach

This descriptive survey was conducted in Maseru around the taxi ranks amongst 48 food handlers and 93 consumers using a semi-structured questionnaire for assessing food handler knowledge, attitudes and practices, open-ended questionnaire for obtaining consumer perceptions and observation checklist.

Findings

Majority of the food handlers were females (60%) and males constituted only (40%). The mean age was 35.5 ± 10.3 and 28.2 ± 9.9 respectively for street vendors and consumers. There was a statistically significant difference in knowledge among the trained and untrained vendors (p = 0040). On average the vendor population that participated in this study was considered to have poor knowledge (scores < 50%) of food safety since they scored 49% ± 11, while 84% of the respondents were considered to have positive attitudes towards food safety. Only 6% of the consumers reported that they never buy street vended foods mainly due to the hygiene issues. The observation checklist showed that the vendors operated under unhygienic conditions and that there was scarcity of clean water supply and hand washing facilities.

Originality/value

This study provides knowledge that was previously unknown about food vending in Lesotho. It has significantly added to the body of knowledge on food safety in Lesotho which can be used to modify policies and structure food safety training for people involved in the informal trade.
A systematic review of faculty research repositories at higher education institutions
Authors: Zibani Patiswa , Rajkoomar Mogiveny , Naicker Nalindren
Published: August 2021

Purpose

This study aims to evaluate faculty research repositories used in higher education institutions, their different levels and functions with regard to research information management. This is revealed through the selected studies reviewed.

Design/methodology/approach

A systematic literature search of journal article studies on research repositories in higher education institutions was carried out on several databases, namely, Ebscohost, Emerald Insight, Science Direct, Sage, Google Scholar, SA e-Publications and citation databases such as Scopus and Web of Science. The systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses guidelines. The time frame for the analysis was 2015 to 2021.

Findings

The findings are presented on the motives for developing faculty research repositories the services provided and benefits derived from faculty research repositories and what is the utilization of faculty research repositories.

Originality/value

The results show that the development of research repositories at the faculty level enhances sharing, analysis, evaluation and preservation of scholarly research produced.
Developing mobility power tactics and strategies: the experiences of Central Eastern European workers in Scotland
Authors: Baxter-Reid Hazel
Published: August 2021

Purpose

The purpose of this article is to examine the tactics and strategies utilised by Central Eastern European (CEE) migrant workers as they strive to develop their mobility power within the employment relationship and outside of the workplace.

Design/methodology/approach

Data is drawn from three qualitative organisational case studies. In total 70 interviews with migrant workers, managers and HR staff were undertaken. There were also nine focus groups with migrant workers across the case studies.

Findings

Developing mobility power is not straightforward, particularly in the context of hard HRM strategies. The majority of CEE workers across the case studies viewed the employment relationship as temporary; however, people found it difficult to develop the mobility power necessary to leave and move to a better job. This can be attributed to a combination of people's individual subjective factors and employment in occupations with limited structural and associational power.

Originality/value

This article engages with debates concerning the agency of migrant workers. Existing studies have focused upon the way in which migrant workers utilise mobility power to leave unfavourable employers. However, this article builds upon current debates by examining how migrant workers develop their mobility power. There is also consideration of the individual and collective dimensions of power.
Does family matter? The moderating role of family involvement on the relationship between CSR and firm performance
Authors: Yeon Jihwan , Lin Michael S. , Lee Seoki , Sharma Amit
Published: August 2021

Purpose

The purpose of this study is to investigate the moderating role of family involvement on the corporate social responsibility (CSR)-firm performance (FP) relationship in the US hospitality industry. Building on agency theory, this study examines how family ownership, management and board control influence the relationship between CSR and FP.

Design/methodology/approach

To examine the moderating effect of family ownership, family management and family board control, this study adopts the two-way fixed-effects model and performs a panel regression analysis with robust standard errors. The sample period spans 1994–2018 and 565 firm-year observations are included.

Findings

This study finds that the impact of CSR on FP is positively moderated by the extent of a firm’s family member involvement. In specific, all three aspects of corporate governance (i.e. ownership, management and board control) positively moderate the relationship between CSR and FP.

Research limitations/implications

Findings of this study yield several recommendations for hospitality managers, including shaping strategic decisions for implementing CSR, by providing a unique perspective that the involvement of founding family members can be helpful in enhancing firm value through CSR activities.

Originality/value

This study sheds light on the further understanding of the CSR-FP link in the hospitality literature. In addition, this study provides practical guidelines for hospitality firms in the context of CSR by revealing possible advantages of strengthened founding family involvement.
Balancing between stability and change in Agile teams
Authors: Lindskog Carin , Netz Johan
Published: August 2021

Purpose

This study aims to create a better understanding of how practitioners implement and work Agile while balancing the tensions arising between stability and change.

Design/methodology/approach

A grounded theory approach was used to explore what happens in practice when software development teams implement and work Agile. The empirical data consists of twenty semi-structured interviews with practitioners working in fourteen different organizations and in six different Agile roles.

Findings

As a result, a substantive theory was presented of continuously balancing between stability and change in Agile teams. In addition, the study also proposes three guidelines that can help organizations about to change their way of working to Agile.

Research limitations/implications

The inherent limitation of a grounded theory study is that a substantial theory can only explain the specific contexts explored in that study. Thus, this study's contribution is a substantial theory that needs to be further developed and improved.

Practical implications

The proposed guidelines can help organizations about to change their way of working to Agile. They can also assist organizations in switching from “doing Agile” to “being Agile”, thus becoming more successful.

Originality/value

The new perspective that this study contributes is the fact that our discovered categories show that several inherent processes are ongoing at the same time in order to balance the need to have both stability and change.
Elucidating technology-based social entrepreneurs’ scale and scope perspectives: a study of environmental and organizational variables
Authors: Bhattacharyya Som Sekhar
Published: August 2021

Purpose

The purpose of this paper was to ascertain how social entrepreneurs were required to recognize their new ventures’ scope and scale of operations. The firm boundary was based upon two dimensions, namely, the scope of the offering and its scale. The objective of this research was to ascertain the thinking regarding this of social entrepreneurs engaged through technology-based social entrepreneurship (TBSE).

Design/methodology/approach

This study conducted an in-depth interview of 26 technology entrepreneurs engaged in social entrepreneurship ventures in India. The interview was carried out based upon a semi-structured open-ended questionnaire. This study undertook thematic and relational content analysis to develop a model of technology-based social entrepreneurs’ venture scoping and scaling.

Findings

This study found that the antecedent variables were the level of support perceived by social entrepreneur from government and at the industry level. Furthermore, the variables’ entrepreneurial and market orientation of social entrepreneurs were found to be the independent variables. These four variables in turn determined the explorative and exploitative horizon of the technology-based social entrepreneurs. Finally, an interplay of these variables ascertained the perspectives of social entrepreneurs engaged in TBSE regarding the notion of their firm’s scope and scale.

Research limitations/implications

The theoretical insights developed in this research study provided an integrated theoretical perspective accommodating both environmental perspectives (industry support and government support) and organizational perspectives (entrepreneurial and market aspects). This was in context of TBSE.

Practical implications

The insights from this research study could provide a robust and comprehensive understanding to social entrepreneurs regarding the strategic thinking towards scale and scope for a technology-based social venture.

Originality/value

To the best of the author’s knowledge, this study was one of the first theoretical works in TBSE towards scaling versus scoping perspectives.