bluuebunny/crossref_metadata_2025 huggingface dataset:
Long live the host! Proteomic analysis reveals possible strategies for parasitic manipulation of its social host
Authors: Hartke Juliane , Ceron-Noriega Alejandro , Stoldt Marah , Sistermans Tom , Kever Marion , Fuchs Jenny , Butter Falk , Foitzik Susanne
Published: December 2022

Parasites with complex lifecycles often manipulate the phenotype of their intermediate hosts to increase the probability of transmission to their definitive hosts. Infection withAnomotaenia brevis, a cestode that usesTemnothorax nylanderiants as intermediate hosts, leads to a multiple-fold extension of host lifespan and to changes in behaviour, morphology, and colouration. The mechanisms behind these changes are unknown, as is whether the increased longevity is achieved through parasite manipulation. Here we demonstrate that the parasite releases proteins into its host with functions that might explain the observed changes. These parasitic proteins make up a substantial portion of the proteome of the hosts’ haemolymph, and thioredoxin peroxidase and superoxide dismutase, two antioxidants, exhibited the highest abundances among them. The largest part of the secreted proteins could not be annotated, indicating they are either novel or severely altered during recent coevolution to function in host manipulation. We also detected shifts in the hosts’ proteome with infection, in particular an overabundance of vitellogenin-like-A in infected ants, a protein that regulates division of labour inTemnothoraxants, which could explain the observed behavioural changes. Our results thus point at two different strategies likely employed by this parasite to manipulate its host – by secretion of proteins with immediate influence on the host’s phenotype and by altering the host’s translational activity. Our findings reveal the intricate molecular interplay required to influence the phenotype of a host and shed light on potential signalling pathways and genes involved in parasite-host communication.
Germline-specific role for unconventional components of the γ-tubulin complex inCaenorhabditis elegans
Authors: Haruta Nami , Sumiyoshi Eisuke , Honda Yu , Terasawa Masahiro , Uchiyama Chihiro , Toya Mika , Kubota Yukihiko , Sugimoto Asako
Published: December 2022

The γ-tubulin complex (γTuC) is a widely conserved microtubule nucleator, but some of its components GCP4–6. Here, we identified two γTuC-associated proteins inC. elegans, namely GTAP−1 and −2, for which apparent orthologs were detected only in the genusCaenorhabditis. Their centrosomal localization was interdependent. In earlyC. elegansembryos, whereas the conserved γTuC component MZT-1/MOZART1 was essential for the localization of centrosomal γ-tubulin, depletion of GTAP-1 and/or −2 caused up to 50% reduction of centrosomal γ-tubulin and precocious disassembly of spindle poles during mitotic telophase. In the adult germline, GTAP-1 and GTP-2 contributed to the efficient recruitment of γTuC to the plasma membrane. Depletion of GTAP-1, but not GTAP-2, severely disrupted both the microtubule array and the honeycomb-like structure in the adult germline.

We propose that GTAP-1 and −2 are unconventional components of γTuC that contribute to the organization of both centrosomal and non-centrosomal microtubules by targeting the γTuC to specific subcellular sites in a tissue-specific manner.

SUMMARY STATEMENT

Haruta et al. show that GTAP-1 and −2, two unconventional components of the γ-tubulin complex (γTuC) inC. elegans, contribute to targeting the γTuC to embryonic centrosomes and germ-cell membrane in adults.
Few temporally distributed brain connectivity states predict human cognitive abilities
Authors: Wehrheim Maren H. , Faskowitz Joshua , Sporns Olaf , Fiebach Christian J. , Kaschube Matthias , Hilger Kirsten
Published: December 2022

Human functional brain connectivity can be temporally decomposed into states of high and low cofluctuation, defined as coactivation of brain regions over time. Rare states of particularly high cofluctuation have been shown to reflect fundamentals of intrinsic functional network architecture and to be highly subject-specific. However, it is unclear whether such network-defining states also contribute to individual variations in cognitive abilities – which strongly rely on the interactions among distributed brain regions. By introducing CMEP, a new eigenvector-based prediction framework, we show that as few as 16 temporally separated time frames (< 1.5% of 10min resting-state fMRI) can significantly predict individual differences in intelligence (N= 263,p< .001). Against previous expectations, individual’s network-defining time frames of particularly high cofluctuation do not predict intelligence. Multiple functional brain networks contribute to the prediction, and all results replicate in an independent sample (N= 831). Our results suggest that although fundamentals of person-specific functional connectomes can be derived from few time frames of highest connectivity, temporally distributed information is necessary to extract information about cognitive abilities. This information is not restricted to specific connectivity states, like network-defining high-cofluctuation states, but rather reflected across the entire length of the brain connectivity time series.
High-throughput profiling of drug interactions in Gram-positive bacteria
Authors: Cacace Elisabetta , Kim Vladislav , Knopp Michael , Tietgen Manuela , Brauer-Nikonow Amber , Inecik Kemal , Mateus André , Milanese Alessio , Mårli Marita Torrissen , Mitosch Karin , Selkrig Joel , Brochado Ana Rita , Kuipers Oscar P. , Kjos Morten , Zeller Georg , Savitski Mikhail M. , Göttig Stephan , Huber Wolfgang , Typas Athanasios
Published: December 2022

Drug combinations present a powerful strategy to tackle antimicrobial resistance, but have not been systematically tested in many bacterial species. Here, we used an automated high-throughput setup to profile ∼ 8000 combinations between 65 antibacterial drugs in three Gram-positive species: the model species,Bacillus subtilisand two prominent pathogens,Staphylococcus aureusandStreptococcus pneumoniae. Thereby, we recapitulate previously known drug interactions, but also identify ten times more interactions than previously reported in the pathogenS. aureus, including two synergies that were also effective in multi-drug resistant clinicalS. aureusisolatesin vitroandin vivo. Interactions were largely species-specific and mostly synergistic for drugs targeting the same cellular process, as observed also for Gram-negative species1. Yet, the dominating synergies are clearly distinct between Gram-negative and Gram-positive species, and are driven by different bottlenecks in drug uptake and vulnerabilities of their cell surface structures. To further explore interactions of commonly prescribed non-antibiotic drugs with antibiotics, we tested 2728 of such combinations inS. aureus, detecting a plethora of unexpected antagonisms that could compromise the efficacy of antimicrobial treatments in the age of polypharmacy. We uncovered even more synergies than antagonisms, some of which we could demonstrate as effective combinations in vivo against multi-drug resistant clinical isolates. Among them, we showed that the antiaggregant ticagrelor interferes with purine metabolism and changes the surface charge ofS. aureus,leading to strong synergies with cationic antibiotics. Overall, this exemplifies the untapped potential of approved non-antibacterial drugs to be repurposed as antibiotic adjuvants. All data can be browsed through an interactive interface (https://apps.embl.de/combact/).
Neural Networks beyond explainability: Selective inference for sequence motifs
Authors: Villié Antoine , Veber Philippe , De Castro Yohann , Jacob Laurent
Published: December 2022

Over the past decade, neural networks have been successful at making predictions from biological sequences, especially in the context of regulatory genomics. As in other fields of deep learning, tools have been devised to extract features such as sequence motifs that can explain the predictions made by a trained network. Here we intend to go beyond explainable machine learning and introduce SEISM, a selective inference procedure to test the association between these extracted features and the predicted phenotype. In particular, we discuss how training a one-layer convolutional network is formally equivalent to selecting motifs maximizing some association score. We adapt existing sampling-based selective inference procedures by quantizing this selection over an infinite set to a large but finite grid. Finally, we show that sampling under a specific choice of parameters is sufficient to characterize the composite null hypothesis typically used for selective inference—a result that goes well beyond our particular framework. We illustrate the behavior of our method in terms of calibration, power and speed and discuss its power/speed trade-off with a simpler data-split strategy. SEISM paves the way to an easier analysis of neural networks used in regulatory genomics, and to more powerful methods for genome wide association studies (GWAS).
Dystrophin is a mechanical tension modulator
Authors: Hofemeier Arne D. , Muenker Till M. , Herkenrath Fabian , Ristau Mariam , Brandt Matthias , Shahriyari Mina , Tiburcy Malte , Zimmermann Wolfram H. , Lenz Christof , Mamchaoui Kamel , Bigot Anne , Gilbert Penney M. , Betz Timo
Published: December 2022

Duchenne muscular dystrophy (DMD) represents the most common inherited muscular disease, where increasing muscle weakness leads to loss of ambulation and premature death. DMD is caused by mutations in the dystrophin gene, and is known to reduce the contractile capacity of muscle tissue bothin vivo, and also in reconstituted systemsin vitro. However, these observations result from mechanical studies that focused on stimulated contractions of skeletal muscle tissues. Seemingly paradoxical, upon evaluating bioengineered skeletal muscles produced from DMD patient derived myoblasts we observe an increase in unstimulated contractile capacity that strongly correlates with decreased stimulated tissue strength, suggesting the involvement of dystrophin in regulating the baseline homeostatic tension level of tissues. This was further confirmed by comparing a DMD patient iPSC line directly to the gene-corrected isogenic control cell line. From this we speculate that the protecting function of dystrophin also supports cellular fitness via active participation in the mechanosensation to achieve and sustain an ideal level of tissue tension. Hence, this study provides fundamental novel insights into skeletal muscle biomechanics and into a new key mechanical aspect of DMD pathogenesis and potential targets for DMD drug development: increased homeostatic tissue tension.
Shortwave-Infrared Line-Scan Confocal Microscope for Deep Tissue Imaging in Intact Organs
Authors: Lingg Jakob G. P. , Bischof Thomas S. , Arús Bernardo A. , Cosco Emily D. , Sletten Ellen M. , Rowlands Christopher J. , Bruns Oliver T. , Chmyrov Andriy
Published: December 2022

Imaging at wavelengths beyond the visible spectrum enables imaging depths of hundreds of microns in intact tissue, making this attractive for volumetric imaging applications. The development of fluorophores with photoemission beyond 1000nm provide the opportunity to develop novel fluorescence microscopes sensitive to those wavelengths. Here, we present a shortwave-infrared line-scan confocal microscope that is capable of deep imaging of biological specimens, as demonstrated by visualization of labelled glomeruli in a fixed uncleared kidney at depths beyond 400 μm. We also show imaging of brain vasculature labelled with the near-infrared organic dye indocyanine green, the shortwave-infrared organic dye Chrom7, and rare earth-doped nanoparticles, thus encompassing the entire spectrum detectable by a typical shortwave-infrared sensitive InGaAs detector.
The origin of floral quartet formation - Ancient exon duplications shaped the evolution of MIKC-type MADS-domain transcription factor interactions
Authors: Rümpler Florian , Tessari Chiara , Gramzow Lydia , Gafert Christian , Blohs Marcus , Theißen Günter
Published: December 2022

During development of flowering plants, some MIKC-type MADS-domain transcription factors (MTFs) exert their regulatory function as heterotetrameric complexes bound to two sites on the DNA of target genes. This way they constitute „floral quartets“ or related „floral quartet-like complexes“ (FQCs), involving a unique multimeric system of paralogous protein interactions. Tetramerisation of MTFs is brought about mainly by interactions of keratin-like (K) domains. The K-domain associated with the more ancient DNA-binding MADS-domain during evolution in the stem group of extant streptophytes (charophyte green algae + land plants). However, whether this was sufficient for MTF tetramerisation and FQC formation to occur, remains unknown. Here, we provide biophysical and bioinformatic data indicating that the ancestral MTFs were not able to form FQCs. According to our data, FQC formation originated in the stem group of land plants in a sublineage of MIKC-type genes termed MIKCC-type genes. In the stem group of this gene lineage, the duplication of the most downstream exon encoding the K-domain led to a C-terminal elongation of the second K-domain helix, thus generating the tetramerisation interface found in extant MIKCC-type proteins. In the stem group of the sister lineage of the MIKCC-type genes, termed MIKC*-type genes, the duplication of two other exons of the K-domain occurred, extending the K-domain at its N-terminal end. Our data indicate that this structural change prevents heterodimerisation between MIKCC-type and MIKC*-type proteins. This way, two largely independent gene regulatory networks could be established, featuring MIKCC-type or MIKC*-type proteins, respectively, that control different aspects of plant development.
Ecology-relevant bacteria drive the evolution of host antimicrobial peptides in Drosophila
Authors: Hanson M.A. , Grollmus L. , Lemaitre B.
Published: December 2022

Antimicrobial peptides are host-encoded immune effectors that combat pathogens and shape the microbiome in plants and animals. However, little is known about how the host antimicrobial peptide repertoire is adapted to its microbiome. Here we characterize the function and evolution of theDiptericinantimicrobial peptide family of Diptera. Using mutations affecting the twoDiptericins(Dpt) ofDrosophila melanogaster, we reveal the specific role ofDptAfor the pathogenProvidencia rettgeriandDptBfor the gut mutualistAcetobacter. Strikingly, presence ofDptA-orDptB-like genes across Diptera correlates with the presence ofProvidenciaandAcetobacterin their environment. Moreover,DptA-andDptB-like sequence predicts host resistance against infection by these bacteria across the genusDrosophila. Our study explains the evolutionary logic behind the bursts of rapid evolution of an antimicrobial peptide family, and reveals how the host immune repertoire adapts to changing microbial environments.
The importance of reaction norms in dietary restriction and ageing research
Authors: Simons Mirre J P , Dobson Adam J
Published: December 2022

Ageing research has progressed rapidly through our ability to modulate the ageing process. Pharmacological and dietary treatments can increase lifespan and have been instrumental in our understanding of the mechanisms of ageing. Recently, several studies have reported genetic variance in response to these anti-ageing interventions, questioning their universal application and making a case for personalised medicine in our field. As an extension of these findings the response to dietary restriction was found to not be repeatable when the same genetic mouse lines were retested. We show here that this effect is more widespread with the response to dietary restriction also showing low repeatability across genetic lines in the fly (Drosophila melanogaster). We further argue that variation in reaction norms, the relationship between dose and response, can explain such conflicting findings in our field. We simulate genetic variance in reaction norms and show that such variation can: 1) lead to over- or under-estimation of treatment responses, 2) dampen the response measured if a genetically heterogeneous population is studied, and 3) illustrate that genotype-by-dose-by-environment interactions can lead to low repeatability of DR and potentially other anti-ageing interventions. We suggest that putting experimental biology and personalised geroscience in a reaction norm framework will aid progress in ageing research.
DNA primase large subunitis an essential plant gene for geminiviruses, putatively priming viral ss-DNA replication
Authors: Siskos Lampros , Antoniou Maria , Riado Jose , Enciso Montserrat , Garcia Carlos , Liberti Daniele , Esselink Danny , Baranovskiy Andrey G. , Tahirov Tahir H. , Visser Richard G.F. , Kormelink Richard , Bai Yuling , Schouten Henk J.
Published: December 2022

The family ofGeminiviridaeconsists of more than 500 circular single-stranded (ss) DNA viral species that can infect numerous dicot and monocot plants. Geminiviruses replicate their genome in the nucleus of a plant cell, taking advantage of the host’s DNA replication machinery. For converting their DNA into double-stranded DNA, and subsequent replication, these viruses rely on host DNA polymerases. However, the priming of the very first step of this process, i.e. the conversion of incoming circular ssDNA into a dsDNA molecule, has remained elusive for almost 30 years. In this study, sequencing of melon (Cucumis melo) accession K18 carrying the Tomato leaf curl New Delhi virus (ToLCNDV) recessive resistance quantitative trait locus (QTL) in chromosome 11, and analyses of DNA sequence data from 100 melon genomes, showed a conservation of a shared mutation in theDNA Primase Large subunit(PRiL) of all accessions that exhibited resistance upon a challenge with ToLCNDV. Silencing of (native)Nicotiana benthamiana PriLand subsequent challenging with three different geminiviruses showed a severe reduction in titers of all three viruses, altogether emphasizing an important role ofPRiLin geminiviral replication. A model is presented explaining the role ofPriLduring initiation of geminiviral DNA replication, i.e. as a regulatory subunit of primase that generates an RNA primer at the onset of DNA replication in analogy toDNA Primase-mediated initiation of DNA replication in all living organisms.
C-ToMExO: Learning Cancer Progression Dynamics from Clonal Composition of Tumors
Authors: Neyshabouri Mohammadreza Mohaghegh , Dimitrakopoulou Smaragda , Lagergren Jens
Published: December 2022

Cancer is an evolutionary process involving the accumulation of somatic mutations in the genome. The tumor’s evolution is known to be highly influenced by specific somatic mutations in so-called cancer driver genes. Cancer progression models are computational tools used to infer the interactions among cancer driver genes by analyzing the pattern of absence/presence of mutations in different tumors of a cohort. In an abundance of subclonal mutations, discarding the heterogeneity of tumors and investigating the interrelations among the driver genes solely based on tumor-level data can result in misleading interpretations. In this paper, we introduce a computational approach to infer cancer progression models from the clone-level data gathered from a cohort of tumors. Our method leverages the rich clone-level data to identify the patterns of interactions among cancer driver genes and produce significantly more robust and reliable cancer progression models. Using a novel efficient Markov Chain Monte Carlo inference algorithm, our method provides outstanding scalability to the rapidly increasing size of available datasets. Using an extensive set of synthetic data experiments, we demonstrate the performance of our inference method in recovering the generative progression models. Finally, we present our analysis of two sub-types of lung cancer using biological multi-regional bulk data.
Unraveling the therapeutic mechanism of deep-brain stimulation
Authors: van den Boom Bastijn J.G. , Fernandez Alfredo Elhazaz , Rasmussen Peter A. , van Beest Enny H. , Parthasarathy Aishwarya , Denys Damiaan , Willuhn Ingo
Published: December 2022

Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of action. To gain mechanistic insight, we monitored neuronal activity in cortico-striatal regions in a mouse model for compulsive behavior, while systematically varying clinically-relevant parameters of internal-capsule DBS. DBS showed dose-dependent effects on both brain and behavior: An increasing, yet balanced, number of excited and inhibited neurons was recruited, scattered throughout cortico-striatal regions, while compulsive grooming decreased. Such neuronal recruitment did not alter basic brain function such as resting-state activity, and only occurred in awake animals, indicating a dependency on network activity. In addition to these widespread effects, we observed specific involvement of the medial orbitofrontal cortex in therapeutic outcomes, which was corroborated by optogenetic stimulation. Together, our findings provide mechanistic insight into how DBS exerts its therapeutic effects on compulsive behaviors.
A practical bacterial biodosimetry procedure to assess performance of lab-scale flow-through ultraviolet water disinfection reactors
Authors: Sperle Philipp , Khan Mohammad S. , Drewes Jörg E. , Wurzbacher Christian
Published: December 2022

Biodosimetry can be used to estimate the fluence of a reactor by determining its ability to inactivate a challenge organism. Especially for small-scale flow-through reactors, inconsistent procedures are reported for bacterial cells. This study aims to develop a standardized, simple procedure for bacterial biodosimetry in flow-through UV systems with relevant biofilm forming bacteria in order to evaluate biofouling control by UV. In particular, the challenge organism, the type of experimental setup and the execution of single steps during biodosimetry with bacterial cells can cause largely deviating results. Since previous work was restricted to model organism, which are not relevant for biofouling, we critically reevaluated all reported steps for the biofilm formingAquabacterium citratiphilumand identified three main factors for biodosimetry reproducibility in flow-through systems: Protractions of cells from negative controls can heavily impact inactivation efficacy, but can be reduced by ordering samples by decreasing fluence. Further, to avoid photo repair, samples must be processed under red light only. Lastly, biofilm forming bacteria can strongly absorb on plastic labware, which requires counter measures in form of special labware and the addition of surfactants. Overall, the developed protocol provides a biodosimetry standardization for bacterial cells of flow-through systems, facilitating reproducibility and transferability of results between studies that use bacterial cells as challenge organism.

Synopsis

Biodosimetry is used to characterize performance of flow-through ultraviolet reactors, but artifacts can occur if not addressed properly.
Individual differences in the effects of salience and reward on impulse control and action selection
Authors: Schutte I. , Schutter D.J.L.G. , Kenemans J.L.
Published: December 2022

Impulse control and adequate decision making are vital functions when it comes to detection and adherence to societal rules, especially in critical circumstances such as the Covid pandemic. In the current study we tested the hypothesis that increasing the salience of environmental cues would be most effective in improving impulse control, as assessed in a stop-signal task, in subjects with low environmental susceptibility as indexed by low pre-stimulus EEG alpha power. In addition, we anticipated that an external-reward intervention improves performance during a Go/No go task, especially in individuals with low task-induced motivation as indexed by low theta/ beta power ratios. High salience of stop signals enhanced stopping performance but there was no difference in responsivity to the salience intervention between participants with high and low EEG alpha power. Individuals with low theta/ beta power ratios responded more accurately when rewards were at stake. Together these results suggest that increasing the salience of external cues may help impulse control in general, whereas the effectiveness of external-reward interventions is higher in individuals with low task-induced motivation.
mapquik: Efficient low-divergence mapping of long reads in minimizer space
Authors: Ekim Barış , Sahlin Kristoffer , Medvedev Paul , Berger Bonnie , Chikhi Rayan
Published: December 2022

DNA sequencing data continues to progress towards longer reads with increasingly lower sequencing error rates. We focus on the critical problem of mapping, or aligning, low-divergence sequences from long reads (PacBio HiFi) to a reference genome, which poses challenges in terms of accuracy and computational resources when using cutting-edge read mapping approaches that are designed for all types of alignments. A natural idea would be to optimize efficiency with longer seeds to reduce the probability of extraneous matches; however, contiguous exact seeds quickly reach a sensitivity limit. We introducemapquik, a novel strategy that creates accurate longer seeds by anchoring alignments through matches ofkconsecutively-sampled minimizers (k-min-mers) and only indexingk-min-mers that occur once in the reference genome, thereby unlocking ultra-fast mapping while retaining high sensitivity. We demonstrate thatmapquiksignificantly accelerates the seeding and chaining steps — fundamental bottlenecks to read mapping — for both the human and maize genomes with>96% sensitivity and near-perfect specificity. On the human genome,mapquikachieves a 30× speed-up over the state-of-the-art toolminimap2, and on the maize genome, a 350× speed-up overminimap2, makingmapquikthe fastest mapper to date. These accelerations are enabled not only by minimizer-space seeding but also a novel heuristic 𝒪(n) pseudo-chaining algorithm, which improves over the long-standing 𝒪(nlogn) bound. Minimizer-space computation builds the foundation for achieving real-time analysis of long-read sequencing data.
Peptide collision cross sections of 22 post-translational modifications
Authors: Will Andreas , Oliinyk Denys , Meier Florian
Published: December 2022

Recent advances have rekindled the interest in ion mobility spectrometry as an additional dimension of separation in mass spectrometry (MS)-based proteomics. It separates ions according to their size and shape in the gas phase. Here, we set out to investigate the effect of 22 different post-translational modifications (PTMs) on the collision cross section (CCS) of peptides. In total, we analyzed ∼4700 pairs of matching modified and unmodified peptide ions by trapped ion mobility spectrometry (TIMS). Linear alignment based on spike-in reference peptides resulted in highly reproducible CCS values with a median coefficient of variation of 0.3%. On a global level, we observed a redistribution in them/zvs. ion mobility space for modified peptides upon changes in their charge state. Pairwise comparison between modified and unmodified peptides of the same charge state revealed median shifts in CCS between – 1.1% (lysine formylation) and +4.5% (O-GlcNAcylation). In general, increasing modified peptide masses were correlated with higher CCS values, in particular within homologous PTM series. However, investigating the ion populations in more detail, we found that the change in CCS can vary substantially for a given PTM depending on the gas phase structure of its unmodified counterpart. In conclusion, our study shows PTM- and sequence-specific effects on the cross section of peptides, which could be further leveraged for proteome-wide PTM analysis.
RanGTP regulates the augmin complex
Authors: Kraus Jodi , Travis Sophie M , King Matthew R , Petry Sabine
Published: December 2022

Spindles are composed of microtubules that must nucleate at the right place and time during mitosis. Spindle microtubule nucleation is regulated by the GTPase Ran, which, through importin-αβ, releases a gradient of spindle assembly factors (SAFs) centered at chromosomes. Branching MT nucleation generates most spindle MTs and requires the augmin complex. InXenopus laevis, Ran can control branching through the SAF TPX2, TPX2 is non-essential in other organisms. Thus, how Ran regulates branching MT nucleation in the absence of TPX2 is unknown. Here, we use in vitro pulldowns and TIRF microscopy to show that augmin is itself a SAF. Augmin directly interacts with both importins through two nuclear localization sequences on the Haus8 subunit, which overlap the MT binding site. Moreover, Ran controls localization of augmin to MTs in bothXenopusegg extract and in vitro. By uncovering that RanGTP directly regulates augmin, we demonstrate how Ran controls branching MT nucleation and, thereby, spindle assembly and cell division.
Integrating human iPSC-derived macrophage progenitors into retinal organoids to generate a mature retinal microglial niche
Authors: Usui-Ouchi Ayumi , Giles Sarah , Ouchi Yasuo , Mills Elizabeth A , Friedlander Martin , Eade Kevin T
Published: December 2022

In the retina, microglia are resident immune cells that are essential for retinal development and function. Retinal microglia play a central role in mediating pathological degeneration in diseases such as glaucoma, retinitis pigmentosa, age-related neurodegeneration, ischemic retinopathy and diabetic retinopathy. Current models of mature human retinal organoids (ROs) derived from iPS cell (hiPSC) do not contain resident microglia integrated into retinal layers. Increasing cellular diversity in ROs by including resident microglia would more accurately represent the native retina and better model diseases in which microglia play a key role. In this study, we develop a new 3Din vitrotissue model of microglia-containing retinal organoids by co-culturing ROs and hiPSC-derived macrophage precursor cells (MPCs). We optimized the parameters for successful integration of MPCs into retinal organoids. We then reproducibly integrate MPCs into ROs where they develop into mature microglia (iMG) as seen by 1) migration to the appropriate anatomical locations; 2) development of a mature resting morphology; and 3) expression of mature microglial markers. We show that while in the ROs, MPCs migrate to the equivalent of the outer plexiform layer where retinal microglia cells reside in healthy retinal tissue. While there, they develop a mature morphology characterized by small cell bodies and long branching processes which is only observedin vivo. During this maturation process these microglia cycle through an activated phase followed by a stable mature phase characterized by cell-type specific microglia markers Tmem119 and P2ry12. This co-culture system may be useful for understanding the pathogenesis of retinal diseases involving retinal microglia and for drug discovery.
Translating Membrane Geometry into Protein Function: Multifaceted Membrane Interactions of Human Atg3 Promote LC3-Phosphatidylethanolamine Conjugation during Autophagy
Authors: Ye Yansheng , Tyndall Erin R. , Bui Van , Bewley Maria C. , Wang Guifang , Hong Xupeng , Shen Yang , Flanagan John M. , Wang Hong-Gang , Tian Fang
Published: December 2022

Autophagosome formation is the hallmark of macroautophagy (herein referred to as autophagy) and requires the covalent conjugation of LC3 proteins (or Atg8 in yeast) to the amino headgroup of PE (phosphatidylethanolamine) lipids. Atg3 is an enzyme that catalyzes the final step of this reaction by transferring LC3 from an LC3-Atg3 intermediate to PEs in targeted membranes. Here, we determine the solution structure of human Atg3 (hAtg3) and demonstrate that the catalytically important regions of hAtg3 are conformationally dynamic. Furthermore, we reveal that these regions and hAtg3’s N-terminal membrane curvature-sensing amphipathic helix concurrently interact with the membrane. These structural studies indicate that hAtg3 exploits a multifaceted membrane-association mechanism to position its catalytic center at the membrane surface and to bring the reaction substrates of LC3 and PE lipids to proximity for effective LC3-PE conjugation. In addition, our studies demonstrate that the interaction of the His266 residue with the membrane is primarily responsible for hAtg3’s pH-dependent activity. Our investigations advance an emerging concept that the interactions of Atg3 with the highly curved membrane rims of the phagophore spatially regulate autophagosome biogenesis.
Reversibility of resistance in a fluctuation test experiment modifies the tail of the Luria-Delbrück distribution
Authors: Bokes Pavol , Hlubinová Anna , Singh Abhyudai
Published: December 2022

We consider a fluctuation test experiment in which cell colonies are grown from a single cell until they reach a given population size, and then they are exposed to treatment. While they grow, the cells may, with a low probability, acquire resistance to treatment and pass it on to their offspring. Unlike the classical Luria–Delbrück fluctuation test and motivated by recent work on drug-resistance acquisition in cancer/microbial cells, we allow for the resistant cell state to switch back to a drug-sensitive state. This modification does not affect the central part of the (Luria–Delbrück) distribution of the number of resistant survivors: the previously developed approximation by the Landau probability density function applies. However, the right tail of the modified distribution deviates from the power law decay of the Landau distribution. We demonstrate that the correction factor is equal to the Landau cumulative distribution function.
Crystal structure and characterization of the sulfamethazine–piperidine salt
Authors: González-González Juan Saulo , Pérez-Espinoza Salvador , Martínez-Martínez Francisco Javier , Pineda-Contreras Armando , Canseco-Martínez Miguel Ángel , Flores-Alamo Marcos , García-Ortega Héctor
Published: December 2022

Sulfamethazine [N
1-(4,6-dimethylpyrimidin-2-yl)sulfanilamide] is an antimicrobial drug that possesses functional groups capable of acting as hydrogen-bond donors and acceptors, which make it a suitable supramolecular building block for the formation of cocrystals and salts. We report here the crystal structure and solid-state characterization of the 1:1 salt piperidinium sulfamethazinate (PPD+·SUL−, C5H12N+·C12H13N4O2S−) (I). The salt was obtained by the solvent-assisted grinding method and was characterized by IR spectroscopy, powder X-ray diffraction, solid-state 13C NMR spectroscopy and thermal analysis [differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)]. Salt I crystallized in the monoclinic space group P21/n and showed a 1:1 stoichiometry revealing proton transfer from SUL to PPD to form salt I. The PPD+ and SUL− ions are connected by N—H+...O and N—H+...N interactions. The self-assembly of SUL− anions displays the amine–sulfa C(8) motif. The supramolecular architecture of salt I revealed the formation of interconnected supramolecular sheets.
Identifying the cavitation erosion stages of AA5083 by electrochemical noise analyses
Authors: Zhu Yesen , Liu Zhe , Qin Zhenbo , Hou Mengyang , Hu Taoyong , Yuan Quan
Published: December 2022

Purpose

The purpose of this paper is to study the cavitation erosion stages of AA5083 by electrochemical noise (EN).

Design/methodology/approach

EN technology including noise resistance and fast Fourier transform were used to characterize the electrochemical process during the cavitation erosion process.

Findings

AA5083 suffers from uniform corrosion during the cavitation erosion process. The whole cavitation erosion process can be divided into three stages: incubation stage, acceleration stage and steady-state stage. EN signals showed obvious differences in different stages of cavitation erosion.

Originality/value

EN technique is a suitable method that can be used to study cavitation erosion mechanism and identify cavitation erosion stages.
An empirical model for assessing consumer behaviour towards hotel sustainable practices: a study from emerging economy
Authors: Sharma Shikha , Mahajan Anupama , Virmani Naveen , Kukreja Gagan , Mehta Kamakshi
Published: December 2022

Purpose

Adopting sustainable practices is highly required in hotels. This study aims to assess consumer behaviour towards adopting sustainable practices in hotels. In addition, mediating role of consumer attitude (CAtt) is assessed between consumer awareness (CA) and willingness to pay.

Design/methodology/approach

An empirical study was carried out to analyse the integrative research model of CA, CAtt and willingness to pay premium price (WTPPP) for sustainable practices adoption in five-star hotels in emerging economies. Responses from 447 respondents were collected and analysed. Structural equation modelling was performed using SPSS 21.0.

Findings

The research outcomes indicate the partial mediation of CAtt between CA and WTPPP. Furthermore, consumer satisfaction has been found to have a moderating effect on the relationship between CAtt and willingness to pay a premium price.

Originality/value

The research results add to the literature by analysing prominent factors affecting willingness to pay premium for adopting sustainable practices in five-star hotels.
A dynamic capabilities approach of Industry 4.0: the experiences of managers operating in two emerging economies
Authors: Vu Oanh Thi Kim , Duarte Alonso Abel , Buitrago Solis M. Alejandra , Goyzueta Samuel , Nguyen Trung , McClelland Robert , Tran Thanh Duc , Nguyen Ngan , Huynh Hoa Thi Ngoc , Atay Erhan
Published: December 2022

Purpose

The purpose of this study is to examine the implementation of Industry 4.0 (I4.0) through the lens of the dynamic capabilities framework. Contrary to most existing research, this study chooses a cross-national viewpoint, exploring companies operating in two emerging economies.

Design/methodology/approach

Semi-structured interviews were conducted with 80 company managers operating in eight industries in Vietnam and Bolivia. The chosen inductive analysis was supported by qualitative content analysis and data structure.

Findings

The analysis reveals 13 conceptual dimensions. For instance, sensing opportunities underlines tangible and intangible “direct prospects”, such as enhanced accuracy, speed and cost effectiveness, whereas “operational management pressures” (sensing threats) identify the dilemma of changing individuals’ mindset, recruitment and addressing financial needs. While there is an overall agreement in key dimensions, differences between managers from both countries also arise, including staff’s adaptation and constant upskilling.

Originality/value

Empirically, this study responds to calls for cross-national studies investigating I4.0 initiatives. In doing so, the data gathered from company managers engaged in business in emerging economies afford new perspectives, with practitioner value. Theoretically, the numerous dimensions emerging from the data analysis provide useful conceptual insights to understand managerial aspects in considering and adapting to I4.0 expectations and requirements. These insights are reinforced by the development of a conceptual model that illuminates the initiatives, efforts and challenges of embracing this phenomenon.
Examining the mediating role of team growth mindset on the relationship of individual mindsets and shared leadership
Authors: Han Soo Jeoung , Xie Lei , Beyerlein Michael , Boehm Rodney
Published: December 2022

Purpose

As a cornerstone of team performance, learning depends on each member’s mindset. Drawing on implicit theories of intelligence, the purpose of this study is to investigate the relationships among individual members’ mindsets and shared leadership (SL) behaviors in design teams and the mediation role of team growth mindset (TGM) on that relationship.

Design/methodology/approach

The authors analyzed survey results based on individuals who participated in an international design competition. To test the hypothesized model, the data was analyzed by using SEM using Mplus 7.

Findings

The results indicated that an individual growth mindset (IGM; but not an individual-fixed mindset) has significant and positive direct effects on a team growth mindset and SL behaviors. In addition, a TGM mediates the relationship between an IGM and SL.

Originality/value

The research discusses several theoretical and practical implications for human resource development professionals and scholars to improve understanding of a TGM and its influence on individual mindsets and SL behaviors.
Governance in Moroccan public hospitals: critical analysis and perspectives for action
Authors: Mourajid Yassmine , Ghafili Asmaa , Chahboune Mohamed , Hilali Abderraouf , Fihri Fassi Chaima
Published: December 2022

Purpose

The purpose of this paper is to analyse the framework of hospital governance in order to understanding the persistence of dysfunctions that have caused the deterioration of the image and quality of Moroccan public hospital services.

Design/methodology/approach

The analysis of the hospital governance model has used a conceptual framework examining four dimensions: institutional, financial, accountability and decision-making dimensions. This framework operationalization was highlighted through a documentary review of the main regulatory and legal texts as well as multiple case studies, using semi-structured interviews with the key stakeholders, considering their expertise and implication in the governance process.

Findings

The study was able to highlight that the governance structure of Moroccan public hospitals has been subject to numerous legislative provisions and modern management instruments. However, the limited autonomy, the resources shortage, dilapidated equipment, the chronic budget deficit, staff demotivation, the lack of accountability mechanisms have led to the deterioration of the quality of care and, hence, to patient's dissatisfaction.

Practical implications

The analysis formed the basis for a series of recommendations. These were mainly aimed at rethinking the current governance model by setting up an institutional policy to improve the current governance structures and monitoring mechanisms of hospitals, as well as revising the instruments for planning and evaluating the provision of care and services according to the real needs of the population, taking into account the financial limits.

Social implications

The hospital governance framework is proving to be a powerful tool for identifying the problems contributing to sub-optimal hospital performance, and calls for policy interventions to improve the organisation organization and delivery of hospital services with greater patient involvement.

Originality/value

This study was the first to analyse the Moroccan hospital governance model, using a comprehensive and structured evaluation methodology designed for public hospitals and supported by extensive data collection which made it possible to offer a broad and in-depth view of the actual functioning of these institutions.
Young people's identities in digital worlds
Authors: Hällgren Camilla , Björk Åsa
Published: December 2022

Purpose

This conceptual paper takes identity, digital technology, young people and education as a combined starting point and suggests how to research young people’s identity practices in and out of school. Today’s young people form their identities in a world that is increasingly imbued by digital technologies. What is evident too is that these technologies and the use of them are not restricted to one single context. Rather, digital technologies mediate multiple contexts simultaneously – to an extent where they collapse. This means that school and leisure time, public and private, digital and analog, virtual and material, time and place, social contexts and audiences, through digital technology, merge in various ways in young people’s identity practices and everyday life.

Design/methodology/approach

Little is known about what identity practices in collapsing contexts means to young people in their lives and how educators and others can support them. Most studies to date investigate digital technology use as a discrete phenomenon and few studies concern young people’s identity practices in contexts, as they occur. In an increasingly digital world, where dependency on digital technologies continues this forms an urgent knowledge gap to bridge. In particular to guide educators, and others, who support young people as they live and learn through interconnected spaces in and out of school. The conceptual approach of this paper is of importance to better understand how to bridge this gap.

Findings

This paper suggests a research approach that extends previous research at the intersection of identity, young people, digital technology by outlining extended ways for thinking about identity in a digital world that can be useful for investigating identity as an existential practice, extending beyond identity representations, in conditions mediated by contemporary digital technologies and in collapsing contexts. What is also included are methodological considerations about researching young people, identity and technology as dynamic research objects, rendering a holistic approach.

Research limitations/implications

It is a conceptual paper that addresses identity, digital technology, young people and education as a combined starting point to outline further research.

Originality/value

The Guided Tour Technique and Social Media Research is suggested as possible methodologies for holistic and ethically sensitive, empirical research on identity, digital technology, young people and education.
Methods of classifying Tunisian investors into homogeneous groups
Authors: Chenini Hajer , Jarboui Anis
Published: December 2022

Purpose

Financial theory is based on the assumption of rationality of individuals. Defenders of behavioral finance recommend that the rationality hypothesis of efficiency theory is too narrow and irrelevant (Barberis and Thaler, 2002). The irrationality of the investor is reflected in his choice and his behaviour. However, his choice depends on the way the problem is formulated and described. The irrational investor does not think in terms of final wealth but rather in terms of gains and losses.

Design/methodology/approach

This research is interested in the methods of classification of the investors in homogeneous groups. In the study, the classification method used to group individual in the sample is the dynamic aggregation method. However, to identify the number of groups to use in this method, the authors also used the hierarchical method on a sub-sample. Thus, to this end the authors present a topological analysis to test the hypothesis of the heterogeneity of Tunisian investor groups in terms of belief.

Findings

The results suggest that the majority of investors are quite irrational. Therefore, the Tunisian investor considers itself irrational because of the presence of several anomalies in its behavior.

Originality/value

This research proposes to help identify the variables that are truly determining in the process of interpreting information. The authors wish to formulate recommendations for the use of information, in order to help professionals and investors in the orientation of the investment strategy. In particular, the authors attempt to indicate the variables to which attention should be paid. In addition, behavioral financial analysis is useful for investors. Thus, taking into account certain irrational phenomena is important to make a decision. In addition, it allows to better identify the investor's own shortcomings and to detect certain negative trends.