bluuebunny/crossref_metadata_2025 huggingface dataset:
MICOS and F1FO-ATP synthase crosstalk is a fundamental property of mitochondrial cristae
Authors: Cadena Lawrence Rudy , Gahura Ondřej , Panicucci Brian , Zíková Alena , Hashimi Hassan
Published: April 2021

Mitochondrial cristae are polymorphic invaginations of the inner membrane that are the fabric of cellular respiration. Both the Mitochondrial Contact Site and Cristae Organization System (MICOS) and the FOF1-ATP synthase are vital for sculpting cristae by opposing membrane bending forces. While MICOS promotes negative curvature at cristae junctions, dimeric FOF1- ATP synthase is crucial for positive curvature at cristae rims. Crosstalk between these two complexes has been observed in baker’s yeast, the model organism of the Opisthokonta supergroup. Here, we report that this property is conserved inTrypanosoma brucei, a member of the Discoba supergroup that separated from Opisthokonta ∼2 billion years ago. Specifically, one of the paralogs of the core MICOS subunit Mic10 interacts with dimeric F1FO-ATP synthase, whereas the other core Mic60 subunit has a counteractive effect on F1FO- ATP synthase oligomerization. This is evocative of the nature of MICOS-F1FO-ATP synthase crosstalk in yeast, which is remarkable given the diversification these two complexes have undergone during almost 2 eons of independent evolution. Furthermore, we identified a highly diverged trypanosome homolog of subunit e, which is essential for the stability of F1FO-ATP synthase dimers in yeast. Just like subunit e, it is preferentially associated with dimers, interacts with Mic10 and its silencing results in severe defects to cristae and disintegration of F1FO-ATP synthase dimers. Our findings indicate that crosstalk between MICOS and dimeric F1FO-ATP synthase is a fundamental property impacting cristae shape throughout eukaryotes.

Importance

Mitochondria have undergone profound diversification in separate lineages that have radiated since the last common ancestor of eukaryotes some eons ago. Most eukaryotes are unicellular protists, including etiological agents of infectious diseases likeTrypanosoma brucei. Thus, the study of a broad range of protists can reveal fundamental features shared by all eukaryotes and lineage-specific innovations. Here we report that two different protein complexes, MICOS and F1FO-ATP synthase, known to affect mitochondrial architecture, undergo crosstalk inT. brucei, just as in baker’s yeast. This is remarkable considering that these complexes have otherwise undergone many changes during their almost two billion years of independent evolution. Thus, this crosstalk is a fundamental property needed to maintain proper mitochondrial structure even if the constituent players considerably diverged.
Antibodies against type-I Interferon: detection and association with severe clinical outcome in COVID-19 patients
Authors: David Goncalves , Mehdi Mezidi , Paul Bastard , Magali Perret , Kahina Saker , Nicole Fabien , Rémi Pescarmona , Christine Lombard , Thierry Walzer , Jean-Laurent Casanova , Alexandre Belot , Jean-Christophe Richard , Sophie Trouillet-Assant
Published: April 2021

Objectives

Impairment of type I interferon (IFN-I) immunity has been reported in critically-ill COVID-19 patients. This defect can be explained in a subset of patients by the presence of circulating autoantibodies (auto-Abs) against IFN-I. We set out to improve the detection and the quantification of IFN-I auto-Abs in a cohort of critically-ill COVID-19 patients, in order to better evaluate the prevalence of these Abs as the pandemic progresses, and how they correlate with the clinical course of the disease.

Methods

The concentration of anti-IFN-α2 Abs was determined in the serum of 84 critically-ill COVID-19 patients who were admitted to ICU in Hospices Civils de Lyon, France using a commercially available kit (Thermo-Fisher, Catalog #BMS217).

Results

A total of 21/84 (25%) critically-ill COVID-19 patients had circulating anti-IFN-α2 Abs above cut-off (>34 ng.mL-1). Among them, 15/21 had Abs with neutralizing activity against IFN-α2, i.e. 15/84 (18%) of critically-ill patients. In addition, we noticed an impairment of the IFN-I response in the majority of patients with neutralizing anti-IFN-α2 Abs. There was no significant difference in the clinical characteristics or outcome of with or without neutralizing anti-IFN-α2 auto-Abs. We detected anti-IFN-α2 auto-Abs in COVID-19 patients’ sera throughout their ICU stay. Finally, we also found auto-Abs against multiple subtypes of IFN-I including IFN-ω.

Conclusions

We reported that 18% of critically-ill COVID-19 patients were positive for IFN-I auto-Abs, confirming that the presence of these antibodies is associated with higher risk of developing a criticall COVID-19 form.
Signatures of COVID-19 severity and immune response in the respiratory tract microbiome
Authors: Merenstein Carter , Liang Guanxiang , Whiteside Samantha A. , Cobián-Güemes Ana G. , Merlino Madeline S. , Taylor Louis J. , Glascock Abigail , Bittinger Kyle , Tanes Ceylan , Graham-Wooten Jevon , Khatib Layla A. , Fitzgerald Ayannah S. , Reddy Shantan , Baxter Amy E. , Giles Josephine R. , Oldridge Derek A. , Meyer Nuala J. , Wherry E. John , McGinniss John E. , Bushman Frederic D. , Collman Ronald G.
Published: April 2021

Rationale

Viral infection of the respiratory tract can be associated with propagating effects on the airway microbiome, and microbiome dysbiosis may influence viral disease.

Objective

To define the respiratory tract microbiome in COVID-19 and relationship disease severity, systemic immunologic features, and outcomes.

Methods and Measurements

We examined 507 oropharyngeal, nasopharyngeal and endotracheal samples from 83 hospitalized COVID-19 patients, along with non-COVID patients and healthy controls. Bacterial communities were interrogated using 16S rRNA gene sequencing, commensal DNA viruses Anelloviridae and Redondoviridae were quantified by qPCR, and immune features were characterized by lymphocyte/neutrophil (L/N) ratios and deep immune profiling of peripheral blood mononuclear cells (PBMC).

Main Results

COVID-19 patients had upper respiratory microbiome dysbiosis, and greater change over time than critically ill patients without COVID-19. Diversity at the first time point correlated inversely with disease severity during hospitalization, and microbiome composition was associated with L/N ratios and PBMC profiles in blood. Intubated patients showed patient-specific and dynamic lung microbiome communities, with prominence of Staphylococcus. Anelloviridae and Redondoviridae showed more frequent colonization and higher titers in severe disease. Machine learning analysis demonstrated that integrated features of the microbiome at early sampling points had high power to discriminate ultimate level of COVID-19 severity.

Conclusions

The respiratory tract microbiome and commensal virome are disturbed in COVID-19, correlate with systemic immune parameters, and early microbiome features discriminate disease severity. Future studies should address clinical consequences of airway dysbiosis in COVID-19, possible use as biomarkers, and role of bacterial and viral taxa identified here in COVID-19 pathogenesis.
Diagnostic Utility of Antigen Detection Rapid Diagnostic Tests for Covid- 19: A Systematic Review and Meta-Analysis
Authors: Ebrahimi Mina , Harmooshi Narges Nazari , Rahim Fakher
Published: April 2021

Background

Early detection of coronavirus disease (COVID-19) infection to improve disease management, becomes the greatest challenge. Despite high sensitivity of RT-PCR, not only it was reported that 20-67% of infected patients have false negative results. Rapid diagnostic tests (RDTs) are widely used as a point-of-care test for SARS-CoV-2 detection in both pharyngeal and blood specimens. To be less time-consuming, not seem so costly, and requiring no special training make it more favorable, but the low sensitivity is the main limitation. Several reports indicated rapid test of blood and pharyngeal samples has the same sensitivity as the RT-PCR, but some reports have lower sensitivity especial in asymptomatic patients.

Methods

In the present survey, we investigate the eligible studies for sensitivity and specificity of rapid tests and explore the factors that influence the result to help better diagnose COVID-19 infection. 20 studies met the inclusion criteria, which impose 33 different tests.

Results

Our findings showed, type of sample, type of assay, time of sampling, and load of virus influence on sensitivity of RDTs.

Conclusion

This research extends our knowledge of how to improve the sensitivity of RDTs to better diagnose of infected patients to address the controlling COVID-19 pandemic.
EgGLUT1 is crucial for the viability of larvae ofEchinococcus granulosus sensus latoby involving its glucose uptake
Authors: Amahong Kuerbannisha , Yan Mingzhi , Li Jintian , Yang Ning , Liu Hui , Bi Xiaojuan , Vuitton Dominique A. , Lin Renyong , Lü Guodong
Published: April 2021

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by infection with the larvae ofEchinococcus granulosus sensu lato(s.l.) cluster. It is urgent to identify novel drug targets and develop new drug candidates against CE. Glucose transporter 1 (GLUT1) is mainly responsible for the transmembrane transport of glucose to maintain its constant cellular availability and is a recent research hotspot as a drug target in various diseases. However, presence and role of GLUT1 inE. granulosus s.l.(EgGLTU1) was unknown. In this study, we cloned a conserved GLUT1 homology gene (named EgGLUT1-ss) fromE. granulosus sensu stricto(s.s.) and found EgGLUT1-ss was crucial for glucose uptake of the protoscoleces ofE. granulosus s.s..WZB117, a GLUT1 inhibitor, inhibited glucose uptake ofE. granulosus s.s.and the viability of the metacestodein vitro.In addition, WZB117 showed potent therapeutic activity inE. granulosus s.s.-infected mice: a 10 mg/kg dose of WZB117 significantly reduced the number and weight of parasite cysts as well as the reference drug, albendazole. Our data have defined EgGLUT1 as a keyE. granulosus s.l.vulnerability target, involved in its glucose uptake from the host; this opens a new avenue to identify drugs with an ideal activity profile for the treatment of CE.
Overview of The Current Progress of Facultative Anaerobic Bacteria in Cancer Biotherapy with TNF-α as Main Mechanism of Action
Authors: Johansson Martina , Nystrom Fredrik H
Published: April 2021

This review article focuses on the use of infectious bacteria as delivery tool for tumour necrosis factor α (TNF-α), a well-studied cytokine, in the context of immunotherapy for cancer treatment. The tumour targeting properties of certain bacteria strains has been known for decades as well as the tumour catabolizing effect of TNF-α. The combination of these two have been studied in murine models for various types of cancer with promising results. Research in this fascinating field is unfortunately uncommon, thus the number of high-quality articles is limited. Search was done via Google Scholar in combination with PubMed, to increase the coverage and find peer-reviewed, original, and primary research articles.

Key findings show that attenuated or genetically modified species of bacteria have fewer side effects and can be effective in delivering cytokines to tumour sites. TNF-α is produced by macrophages/monocytes during acute inflammation or infection, thus can be triggered by infectious bacteria which in turn induce apoptosis. The cytotoxic effect of the bacteria can be enhanced with localized irradiation. Promising results have been shown in bladder, breast, colon, glial, lung, ovarian, pancreatic, prostate, and renal cancer cells.

The need for better, safer, and more effective cancer treatment is apparent as traditional chemotherapy and radiation can cause a lot of harm for the patient, and not necessarily prolong the lifespan. The success-rate for these treatments vary greatly depending on the type of cancer, but for tumours that cannot be surgically removed the outcome is generally quite poor. A drawback of chemotherapy is that tumours can grow resistant to the treatment while healthy cells continue to be exposed, increasing the risk of severe side effects. Different types of biological therapies are a modern and possibly safer approach, even though immunotherapy comes with substantial risks. Using the innate immune system to fight tumour cells is not always safe, because uncontrolled and excessive release of pro-inflammatory signalling molecules can result in multisystem organ failure and death. This phenomenon is called cytokine release syndrome (cytokine storm) and is one of the major risks of immunotherapy. However, tailored biological therapies have proven their effectiveness for a wide range of cancer types, and the next step in this evolution is to genetically engineer both delivery systems and mechanisms of action. This approach can be combined with the traditional radiation and chemotherapy for increased effectiveness, even if biological therapies as a stand-alone treatment, can be a goal for the future.
Design considerations for workflow management systems use in production genomics research and the clinic
Authors: Ahmed Azza E , Allen Joshua M , Bhat Tajesvi , Burra Prakruthi , Fliege Christina E , Hart Steven N , Heldenbrand Jacob R , Hudson Matthew E , Istanto Dave Deandre , Kalmbach Michael T , Kapraun Gregory D , Kendig Katherine I , Kendzior Matthew Charles , Klee Eric W , Mattson Nate , Ross Christian A , Sharif Sami M , Venkatakrishnan Ramshankar , Fadlelmola Faisal M , Mainzer Liudmila S
Published: April 2021

Background

The changing landscape of genomics research and clinical practice has created a need for computational pipelines capable of efficiently orchestrating complex analysis stages while handling large volumes of data across heterogeneous computational environments. Workflow Management Systems (WfMSs) are the software components employed to fill this gap.

Results

This work provides an approach and systematic evaluation of key features of popular bioinformatics WfMSs in use today: Nextflow, CWL, and WDL and some of their executors, along with Swift/T, a workflow manager commonly used in high-scale physics applications. We employed two use cases: a variant-calling genomic pipeline and a scalability-testing framework, where both were run locally, on an HPC cluster, and in the cloud. This allowed for evaluation of those four WfMSs in terms of language expressiveness, modularity, scalability, robustness, reproducibility, interoperability, ease of development, along with adoption and usage in research labs and healthcare settings. This article is trying to answer,“which WfMS should be chosen for a given bioinformatics application regardless of analysis type?”.

Conclusions

The choice of a given WfMS is a function of both its intrinsic language and engine features. Within bioinformatics, where analysts are a mix of dry and wet lab scientists, the choice is also governed by collaborations and adoption within large consortia and technical support provided by the WfMS team/community. As the community and its needs continue to evolve along with computational infrastructure, WfMSs will also evolve, especially those with permissive licenses that allow commercial use. In much the same way as the dataflow paradigm and containerization are now well understood to be very useful in bioinformatics applications, we will continue to see innovations of tools and utilities for other purposes, like big data technologies, interoperability, and provenance.
Stimulation with mycobacterial glycolipids and PPD reveals different innate immune response profiles in active and latent TB
Authors: Silva Carolina S , Sundling Christopher , Folkeson Elin , Fröberg Gabrielle , Nobrega Claudia , Canto-Gomes João , Chambers Benedict J. , Lakshmikanth Tadepally , Brodin Petter , Bruchfeld Judith , Nigou Jerome , Correia-Neves Margarida , Källenius Gunilla
Published: April 2021

Upon infection withMycobacterium tuberculosis(Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and PPD. At 24 h and 5 days of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM mainly affected antigen-presenting cells to produce both proinflammatory (IL-2, IL-6, IL-17A, TNF-αand GM-CSF), and IL-4 and IL-10 cytokines, but not IFN-γ. LAM triggered a similar, albeit weaker, response. By contrast, PPD induced an increase in IFN-γ-producing cells. Moreover, PPD also led to increased numbers of IL-2, IL-6, IL-10, IL-17A, TNF-αand GrzB-producing cells. Treatment with an anti-TLR2 antibody led to partial inhibition of PIM-induced IL-6 production in myeloid cells, suggesting that PIM induces IL-6 production through TLR2. Expansion of monocyte subsets in response to PIM or LAM was reduced in both ATB and LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern in Mtb-infected individuals.
Collective border cell migration requires the zinc transporter Catsup to limit endoplasmic reticulum stress
Authors: Guo Xiaoran , Dai Wei , Montell Denise
Published: April 2021

Collective cell migration is critical for normal development, wound healing, and in tumor progression and metastasis. Border cells in the Drosophila ovary provide a genetically tractable model to identify molecular mechanisms that drive this important cell behavior. In an unbiased screen for defects in border cell migration in mosaic clones, we identified a mutation in thecatsupgene. Catsup, the Drosophila ortholog of Zip7, is a large, multifunctional, transmembrane protein of the endoplasmic reticulum (ER), which has been reported to negatively regulate catecholamine biosynthesis, to regulate Notch signaling, to function as a zinc transporter, and to limit ER stress. Here we report thatcatsupknockdown caused ER stress in border cells and that ectopic induction of ER stress was sufficient to block migration. Notch and EGFR trafficking were also disrupted. Wild type Catsup rescued the migration defect but point mutations known to disrupt the zinc ion transport of Zip7 did not. We conclude that migrating cells are particularly susceptible to defects in zinc transport and ER homeostasis.
Single-Molecule Tracking of Chromatin-Associated Proteins in the C. elegans Gonad
Authors: von Diezmann Lexy , Rog Ofer
Published: April 2021

1.

Biomolecules are distributed within cells by molecular-scale diffusion and binding events that are invisible in standard fluorescence microscopy. These molecular search kinetics are key to understanding nuclear signaling and chromosome organization, and can be directly observed by single-molecule tracking microscopy. Here, we report a method to track individual proteins within intact C. elegans gonads and apply it to study the molecular dynamics of the axis, a proteinaceous backbone that organizes meiotic chromosomes. Using either fluorescent proteins or enzymatically ligated dyes, we obtain multi-second trajectories with a localization precision of 15-25 nm in nuclei actively undergoing meiosis. Correlation with a reference channel allows for accurate measurement of protein dynamics, compensating for movements of the nuclei and chromatin within the gonad. We find that axis proteins exhibit either static binding to chromatin or free diffusion in the nucleoplasm, and we separately quantify the motion parameters of these distinct populations. Freely diffusing axis proteins selectively explore chromatin-rich regions, suggesting they are circumventing the central phase-separated region of the nucleus. This work demonstrates that single-molecule microscopy can infer nanoscale-resolution dynamics within living tissue, expanding the possible applications of this technique.
Dynamic prospect theory - two core economic decision theories coexist in the gambling behavior of monkeys
Authors: Tymula Agnieszka , Imaizumi Yuri , Kawai Takashi , Kunimatsu Jun , Matsumoto Masayuki , Yamada Hiroshi
Published: April 2021

Research in behavioral economics and reinforcement learning has given rise to two influential theories describing human economic choice under uncertainty. The first, prospect theory, assumes that decision-makers usestaticmathematical functions, utility and probability weighting, to calculate the values of alternatives. The second, reinforcement learning theory, posits thatdynamicmathematical functions update the values of alternatives based on experience through reward prediction error (RPE). To date, these theories have been examined in isolation without reference to one another. Therefore, it remains unclear whether RPE affects a decision-maker’s utility and/or probability weighting functions, or whether these functions are indeed static as in prospect theory. Here, we propose a dynamic prospect theory model that combines prospect theory and RPE, and test this combined model using choice data on gambling behavior of captive macaques. We found that under standard prospect theory, monkeys, like humans, had a concave utility function. Unlike humans, monkeys exhibited a concave, rather than inverse-S shaped, probability weighting function. Our dynamic prospect theory model revealed that probability distortions, not the utility of rewards, solely and systematically varied with RPE: after a positive RPE, the estimated probability weighting functions became more concave, suggesting more optimistic belief about receiving rewards and over-weighted subjective probabilities at all probability levels. Thus, the probability perceptions in laboratory monkeys are not static even after extensive training, and are governed by a dynamic function well captured by the algorithmic feature of reinforcement learning. This novel evidence supports combining these two major theories to capture choice behavior under uncertainty.

Significance statement

We propose and test a new decision theory under uncertainty by combining pre-existing two influential theories in the neuroeconomics: prospect theory from economics and prediction error theory from reinforcement learning. Collecting a large dataset (over 60,000 gambling decisions) from laboratory monkeys enables us to test the hybrid model of these two core decision theories reliably. Our results showed over-weighted subjective probabilities at all probability levels after lucky win, indicating that positive prediction error systematically bias decision-makers more optimistically about receiving rewards. This trial-by-trial prediction-error dynamics in probability perception provides outperformed performance of the model compared to the standard static prospect theory. Thus, both static and dynamic elements coexist in monkey’s risky decision-making, an evidence contradicting the assumption of prospect theory.
Relish plays a dynamic role in the niche to modulateDrosophilablood progenitor homeostasis in development and infection
Authors: Ramesh Parvathy , Dey Nidhi Sharma , Kanwal Aditya , Mandal Sudip , Mandal Lolitika
Published: April 2021

Immune challenges demand the gearing up of basal hematopoiesis to combat infection. Little is known about how during development, this switch is achieved to take care of the insult. Here, we show that the hematopoietic niche of the larval lymph gland ofDrosophilasenses immune challenge and reacts to it quickly through the nuclear factor-κB (NF-κB), Relish, a component of the immune deficiency (Imd) pathway. During development, Relish is triggered by ecdysone signaling in the hematopoietic niche to maintain the blood progenitors. Loss of Relish causes an alteration in the cytoskeletal architecture of the niche cells in a Jun Kinase dependent manner, resulting in the trapping of Hh implicated in progenitor maintenance. Notably, during infection, downregulation of Relish in the niche tilts the maintenance program towards precocious differentiation, thereby bolstering the cellular arm of the immune response.
Single-molecule imaging of cytoplasmic dyneinin celluloreveals the mechanism of motor activation and cargo movement
Authors: Tirumala Nireekshit Addanki , Redpath Gregory , Skerhut Sarah Viktoria , Dolai Pritha , Kapoor-Kaushik Natasha , Ariotti Nicholas , Kumar K Vijay , Ananthanarayanan Vaishnavi
Published: April 2021

Cytoplasmic dynein 1 (dynein) is the primary minus end-directed motor protein in most eukaryotic cells. Dynein remains in an inactive conformation until the formation of a tripartite complex comprising dynein, its regulator dynactin and a cargo adaptor. How this process of dynein activation occurs is unclear, since it entails the formation of a three-protein complex inside the crowded environs of a cell. Here, we employed live-cell, single-molecule imaging to visualise and track fluorescently tagged dynein. First, we observed that only ~30% of dynein molecules that bound to the microtubule (MT) engaged in minus end-directed movement, and that too for a short duration of ~0.6 s. Next, using high-resolution imaging in live and fixed cells, and using correlative light and electron microscopy, we discovered that dynactin and endosomal cargo remained in proximity to each other and to MTs. We then employed two-colour imaging to visualise cargo movement effected by single motor binding. Finally, we performed long-term imaging to show short movements are sufficient to drive cargo to the perinuclear region of the cell. We then used these discoveries as the basis for a stochastic model incorporating dynamic motors binding to cargo located along MTs, and also developed a coarse-grained 3-state run- and-tumble particle (RTP) model for the cargo that quantitatively recapitulates the emergent statistics of cargo movement. Taken together, we discovered a search mechanism that is facilitated by dynein’s frequent MT binding-unbinding kinetics: (1) in a futile event when dynein does not encounter cargo anchored in proximity to the MT, dynein dissociates and diffuses into the cytoplasm, (2) when dynein encounters cargo and dynactin upon MT-binding, it moves cargo in a short run. Several of these short runs are undertaken in succession for long-range directed movement. In conclusion, we demonstrate that dynein activation and cargo capture are coupled in a step that relies on the reduction of dimensionality to enable minus end-directed transportin cellulo, and that complex cargo behaviour emerges from stochastic motor-cargo interactions.
Identification of arginine phosphorylation inMycolicibacterium smegmatis
Authors: Ogbonna Emmanuel C. , Anderson Henry R. , Schmitz Karl R.
Published: April 2021

Tuberculosis is a leading cause of worldwide infectious mortality. The prevalence of multidrug-resistantMycobacterium tuberculosis(Mtb) infections drives an urgent need to exploit new drug targets. One such target is the ATP-dependent protease ClpC1P1P2, which is strictly essential for viability. However, few proteolytic substrates of mycobacterial ClpC1P1P2 have been identified to date. Recent studies inBacillus subtilishave shown that the orthologous ClpCP protease recognizes proteolytic substrates bearing post-translational arginine phosphorylation. While several lines of evidence suggest that ClpC1P1P2 is similarly capable of recognizing phosphoarginine-bearing proteins, the existence of phosphoarginine modifications in mycobacteria has remained in question. Here, we confirm the presence of post-translational phosphoarginine modifications inMycolicibacterium smegmatis(Msm), a nonpathogenic surrogate ofMtb. Using a phosphopeptide enrichment workflow coupled with shotgun phosphoproteomics, we identify arginine phosphosites on several functionally diverse targets within theMsmproteome. Interestingly, phosphoarginine modifications are not upregulated by heat stress, suggesting divergent roles in mycobacteria andBacillus. Our findings provide new evidence supporting the existence of phosphoarginine-mediated proteolysis by ClpC1P1P2 in mycobacteria and other actinobacterial species.
Magnetic wire active microrheology of human respiratory mucus
Authors: Radiom Milad , Hénault Romain , Mani Salma , Iankovski Aline Grein , Norel Xavier , Berret Jean-François
Published: April 2021

Mucus is a viscoelastic gel secreted by the pulmonary epithelium in the tracheobronchial region of the lungs. The coordinated beating of cilia in contact with the gel layer moves mucus upwards towards pharynx, removing inhaled pathogens and particles from the airways. The efficacy of this clearance mechanism depends primarily on the rheological properties of mucus. Here we use a magnetic wire based microrheology technique to study the viscoelastic properties of human mucus collected from human bronchus tubes. The response of wires between 5 and 80 µm in length to a magnetic rotating field is monitored by optical time-lapse microscopy and analyzed using constitutive equation models of rheology, including Maxwell and Kelvin-Voigt. The static shear viscosity and elastic modulus can be inferred from low frequency (10−3− 10 rad s−1) measurements, leading to the evaluation of the mucin network relaxation time. This relaxation time is found to be widely distributed, from one to several hundred seconds. Mucus is identified as a viscoelastic liquid with an elastic modulus of 2.5 ± 0.5 Pa and a static viscosity of 100 ± 40 Pa s. Our work shows that beyond the established spatial variations in rheological properties due to microcavities, mucus exhibits secondary inhomogeneities associated with the relaxation time of the mucin network that may be important for its flow properties.
The accuracy of NMR protein structures in the Protein Data Bank
Authors: Fowler Nicholas J , Sljoka Adnan , Williamson Mike P
Published: April 2021

We recently described a method, ANSURR, for measuring the accuracy of NMR protein structures. It is based on comparing residue-specific measures of rigidity from backbone chemical shifts via the random coil index, and from structures. Here, we report the use of ANSURR to analyse NMR ensembles within the Protein Data Bank (PDB). NMR structures cover a wide range of accuracy, which improved over time until about 2005, since when accuracy has not improved. Most structures have accurate secondary structure, but are too floppy, particularly in loops. There is a need for more experimental restraints in loops. The best current accuracy measures are Ramachandran distribution and number of NOE restraints per residue. The precision of structure ensembles correlates with accuracy, as does the number of hydrogen bond restraints per residue. If a structure contains additional components (such as additional polypeptide chains or ligands), then their inclusion improves accuracy. Analysis of over 7000 PDB NMR ensembles is available via our websiteansurr.com.
Millennial turnover intentions: how can B-schools make a difference?
Authors: Acharya Pragnya , Garcia-Tapial Joaquin , Jena Lalatendu Kesari
Published: April 2021

Purpose

The article intends to instigate a new thought process for management institutions to reshape their curriculum and design their teaching around mitigating the rising attrition among millennials. As there is a huge influx of millennials into the corporate world, it is much required that we concentrate on the quality of talent produced and ensure that this talent gives long term results for organizations aiming at a sustained development for both, the organizations as well as the millennial workforce.

Design/methodology/approach

A survey was carried out to seek views from academicians and senior practitioners, who often work as mediating and moderating factors in the process.

Findings

The managers need to understand that apart from developing retention strategies, the target employees should also have the intention to stay, which cannot be instilled by the organization and should be taught along with their management education. It is only to save the time and money of the organization and easing their struggles by developing at the grass-root level, which is in the classrooms where the managers are created.

Originality/value

Much research has been done on revamping teaching pedagogy and including more industry-specific skills into the management education. This article seeks to pin point the attitudinal development of the outgoing managers, which has a high intention towards job hopping.
Design modification of iron ore bearing transfer chute using discrete element method
Authors: Basu Saprativ , Chakrabarty Arijit , Nag Samik , Behera Kishore , Bandyopadhyay Brati , Grima Andrew Phillip , Ghosh Probal
Published: April 2021

Purpose

The dryer feed chute of the pellet plant plays an important role in the pelletizing process. The chute discharges sticky and moist iron ore fines (<1 mm) to the inline rotary dryer for further processing. Since the inception of the installation of the dryer feed chute, the poor flowability of the feed materials has caused severe problems such as blockages and excessive wear of chute liners. This leads to high maintenance costs and reduced lifetime of the liner materials. Constant housekeeping is needed for maintaining the chute and reliable operation. The purpose of this study is to redesign the dryer feed chute to overcome the above challenges.

Design/methodology/approach

The discrete element method (DEM) has been used to model the flow of cohesive materials through the transfer chute. Physical experiments have been performed to understand the most severe flow conditions. A DEM material model is also developed for replicating the worst-case material condition. After identifying the key problem areas, concept designs were proposed and simulated to assess the design improvements to increase the reliability of chute operation.

Findings

Flow simulations correlated well with the existing flow behavior of the iron ore fines inside the chute. The location of the problematic areas has been validated with that of the previously installed chute. Subsequently, design modifications have been proposed. This includes modification of deflector plate and change in slope and cross-section of the chute. DEM simulations and analysis were conducted after incorporating these design changes. A comparison in the average velocity of particle and force on chute wall shows a significant improvement using the proposed design.

Originality/value

Method to calibrate DEM material model was found to provide accurate prediction and modeling of the flow behavior of bulk material through the real transfer chute. DEM provided greater insight into the performance of the chute especially modeling cohesive materials. DEM is a valuable design tool to assist chute designers troubleshoot and verify chute designs. DEM provides a greater ability to model and assess chute wear. This technique can help in achieving a scientific understanding of the flow properties of bulk solids through transfer chute, hence eliminate challenges, ensuring reliable, uninterrupted and profitable plant operation. This paper strongly advocates the use of calibrated DEM methodology in designing bulk material handling equipment.
COVID-19 and its impact on visitation and management at US national parks
Authors: Templeton A.J. , Goonan Kelly , Fyall Alan
Published: April 2021

Purpose

National Park Service (NPS) units generate a significant economic impact for states and local gateway communities across the USA. Utah is home to 13 NPS units with visitation accounting for 18% of the state's US$9.75bn tourism economy in 2018. Twelve NPS units, including five national parks, are located in Southern Utah, driving an economy that is heavily dependent on tourism. This paper examines the challenges and opportunities for visits to national parks post-COVID-19, generally and in the specific context of Southern Utah. Although the assumption is that visits to national parks will recover quickly, this paper will critically examine how visitation may change and what adaptive measures and alternative forms of unit management may be necessary.

Design/methodology/approach

By adopting a holistic-inductive paradigm, this paper utilizes a descriptive case study approach. Data were collected across a variety of mediums focusing on interviews with key stakeholders in and around Southern Utah.

Findings

The results from this study highlight the various challenges faced in parks and gateway communities vis-à-vis changing patterns of visitation, adaptive measures and alternative forms of unit management necessary due to COVID-19 and their impact on the future management and marketing of national parks for touristic purposes.

Originality/value

This paper examines the impacts of COVID-19 on an often-neglected yet significant area within tourism, yielding implications for industry, visitors and destination communities.
Educational leadership and innovative teaching practices: a polynomial regression and response surface analysis
Authors: Paletta Angelo , Alimehmeti Genc , Mazzetti Greta , Guglielmi Dina
Published: April 2021

Purpose

This study explores the factors that explain the adoption of innovative teaching practices within schools and how this is determined by the different perceptions of principals and teachers.

Design/methodology/approach

The authors use the self-other agreement to measure the difference between the principal and teachers' rating based on the responses of 255 principals and 10,415 teachers, applying polynomial regression with surface analysis to examine the in-agreement/disagreement of self- and other-ratings.

Findings

Results indicate that schools where principals and teachers agree on the level of collaborative culture, learning climate, professional development and instructional leadership are associated with higher innovative teaching practices, creating opportunities for stimulating learning environments. In addition, the adoption of innovative professional practices is more likely to result when there is disagreement with teacher over-rating the factors.

Practical implications

It has practical implications for developing strategies aimed at encouraging the implementation of innovative teaching practices among teachers and it extends the research on teachers' professional practices by using self-other agreement data collection method and surface analysis.

Originality/value

The vast collection of data provide a unique investigation opportunity of the effects of collaborative culture, learning climate, professional development and instructional leadership on innovative teaching in Italy.
Early childhood centre directors coping with stress: firefighters and oracles
Authors: Kristiansen Elsa , Rydjord Tholin Kristin , Bøe Marit
Published: April 2021

Purpose

Early childhood education (ECE) centre directors have to meet various leadership demands at present, and this has become even more important in a time of extensive policy changes. There is little research on work-related stress from the perspective of ECE directors. The purpose of this study was therefore to enhance one’s knowledge of (a) what ECE centre directors perceive to be work-related stressors; (b) what causes stressful situations; and (c) how they cope with the identified stressors.

Design/methodology/approach

Eighty directors from three groups in part-time leadership education programmes participated between 2017 and 2020. Data was collected through class discussions and whiteboard notes, focus group interviews with 24 directors and student role-play scenarios that were acted out in class.

Findings

The findings illustrated three main categories of stressors: an overwhelming number of administrative tasks, leading others and lack of social support. Unexpected findings were a lack of knowledge about coping strategies and a need for more resources so that directors can focus on pedagogical leadership.

Research limitations/implications

The study has been done in the Norwegian educational context with Norwegian ECE centre directors participating in a leadership programme. Several qualitative methods were used on three groups of centre directors. These limitations must be considered when generalizing.

Practical implications

The results can be used as guidance for supporting ECE centre directors, owners and policymakers in how to develop and sustain leadership and increase well-being and work satisfaction.

Originality/value

The current study is among the few ones focussing on perceived stressors among centre directors and the consequent coping in the early childhood setting.
Emotional self-efficacy and workplace psychological health in emergency dispatchers
Authors: Huard Charlotte , Deschênes Andrée-Ann , Rioux Charles-Antoine
Published: April 2021

Purpose

The main purpose of this research is to establish the relationships between emotional self-efficacy and workplace psychological health for emergency dispatchers.

Design/methodology/approach

A correlational design was used to validate results of the study. Between December 2018 and February 2019, a secure online questionnaire was sent to dispatchers through four emergency call centers. Participation was voluntary. A total of 257 emergency dispatchers participated in this study. Gilbert et al.’s (2011) scale of workplace psychological health and Deschênes et al.’s (2019) scale of emotional self-efficacy were used. Multiple linear regression and Pearson's correlation tests were run using the SPSS 25 program in order to establish relationships between the two variables.

Findings

A total of three emotional competencies positively affect workplace psychological well-being (PWB), i.e. self-efficacy beliefs on managing one's own emotions, on managing other people' emotions and on using one's own emotions. As regards to psychological distress (PD), it is negatively correlated to self-efficacy beliefs on managing and using one's own emotions.

Research limitations/implications

One of the study's theoretical contributions is to broaden the scientific knowledge of emergency service dispatching, in addition to opening up a new field of study in workplace people management.

Practical implications

These scientific findings therefore show the importance of emotional self-efficacy in the workplace. The manager or the dispatch leader should focus on developing the following three emotional skills: self-efficacy in managing emotions, managing the emotions felt by others and using emotions. Training allowing the development of these emotional skills should be considered and would be beneficial for emergency dispatchers to maximize their well-being at work.

Originality/value

To the best of the authors’ knowledge, no other study has focused on emergency dispatchers and included the emotional self-efficacy and workplace mental health variables.
Being mobile: a call for collaborative innovation practices?
Authors: Antonczak Laurent , Burger-Helmchen Thierry
Published: April 2021

Purpose

The purpose of this study is to examine mobile technology as being a key apparatus and interface for collaborative innovation, which allows organisations to develop their information ecology.

Design/methodology/approach

The qualitative research was performed by in-depth interviews, observations and field notes. The eight main interviews are supported by an interdisciplinary narrative literature review of knowledge management and associated fields.

Findings

This study validates the following propositions: mobile technology can offer users timely information, mobile technology can foster collaboration beyond physical and organisational boundaries, in general, mobile technology enables a wider amount of interactions between people. Thereby, this paper draws some implications about the knowledge management of creative (and non-creative) workers.

Research limitations/implications

The collected data sheds light on how organisations and individuals positioned themselves about mobile technology co-creative practices before the COVID era. Therefore, it shall be pertinent to further investigate these findings through a quantitative approach to better ascertain path models and to strengthen the new results with another qualitative perspective, in the post-COVID era.

Practical implications

The study highlights how mobile devices are facilitating collaborative innovation practices by improving management decisions, enabling new business and/or operating models, developing a flow of ideas inner/outer an organisation and fostering the ability to make innovation.

Social implications

Mobile technology transforms the way to work (knowledge creation and/or conversion) and it changes the relations between collaborators in a working environment (beyond physical boundaries). This study deciphers how a creative and/or decision-making person can change their work schedule and/or routines based on the use of mobile devices.

Originality/value

The added value of this transdisciplinary study is that it improves research on collaborative innovation and collective knowledge by revealing three pertinent characteristics of mobile technology: enabling quick decision; connecting with a glocal network and fostering collective creativity. It also creates a bridge between the fields of education and business.
Family across borders social capital and diaspora entrepreneurial preparedness
Authors: Karayianni Eva , Hadjielias Elias , Glyptis Loukas
Published: April 2021

Purpose

The purpose of this paper is to study the way in which family ties influence the entrepreneurial preparedness of the diaspora family business owner.

Design/methodology/approach

In-depth interviews were carried out with 15 Cypriot family business owners hosted in various countries. The paper draws on social capital theory and uses an abductive analytical approach.

Findings

The findings of this paper illustrate that family ties coming from the family across borders play a significant role for diaspora family business owners’ entrepreneurial preparedness. Hidden values deriving from the interpersonal relationships within the family across borders drive the diaspora family business owners to learn upon self-reflection and become entrepreneurially prepared, led by both urgency and esteem.

Practical implications

This study provides practical implications for the entrepreneurial preparedness of diaspora family business owners and those who wish to become family business owners in a diaspora context.

Originality/value

This study contributes theoretically through the conceptualization of “family across borders social capital” and “diaspora entrepreneurial preparedness”. It also contributes empirically to the fields of diaspora family business, entrepreneurial learning and diaspora entrepreneurship through new knowledge regarding the role of family across borders social capital in the entrepreneurial preparedness of the diaspora family business owner.