bluuebunny/crossref_metadata_2025 huggingface dataset:
The stability of NPM1 oligomers regulated by acidic disordered regions controls the quality of liquid droplets
Authors: Okuwaki Mitsuru , Ozawa Shin-Ichiro , Ebine Shuhei , Juichi Motoki , Umeki Tadanobu , Niioka Kazuki , Kikuchi Taiyo , Tanaka Nobutada
Published: January 2023

A nucleolus is a typical membrane-less nuclear body that is formed by liquid–liquid phase separation (LLPS) of its components. A major component that drives LLPS in the nucleolus is nucleophosmin (NPM1). The oligomer formation and inter-oligomer interactions of NPM1 are suggested to cooperatively contribute to the induction of LLPS. However, the molecular mechanism of how the quality of the liquid droplets formed by NPM1 is regulated is currently not well understood. In this manuscript, we revealed the regulatory mechanism of NPM1 oligomer formation and its relationship with the ability to form liquid droplets. Molecular dynamics simulations and mutant protein analyses suggest that the acidic amino acids in the N-terminal and central disordered regions of NPM1 disturb the key interactions between monomers. We also demonstrate that mutants with attenuated oligomer stability form liquid droplets as do the wild-type; the fluidity of the formed liquid droplets was greater than that of the wild-type. These results suggest that the stability of NPM1 oligomers is a critical determinant of liquid droplet quality. Furthermore, we observed that when the net negative charges in the acidic disordered regions were increased by phosphomimetic mutations at Ser125, the NPM1 oligomer stability decreased, which increased the fluidity of the liquid droplets. Our results provide a novel mechanistic insight into how nucleolar dynamics are regulated during the cell cycle.
Aspartyl protease in the secretome of honey bee trypanosomatid parasite is essential for the efficient infection of host
Authors: Yuan Xuye , Sun Jianying , Kadowaki Tatsuhiko
Published: January 2023

Exoproteome represents the proteome consisting of all secreted proteins and proteins derived from the cell surface and lysed cell. The exoproteome of the trypanosomatid parasite should interact with the host cells and the associated microbiota; however, the roles of infecting insect hosts are not yet understood. To uncover the functions of exoproteome, we identified the exoproteome of honey bee trypanosomatid parasite,Lotmaria passim, and found that approximately 28 % are shared with that common betweenLeishmaniaspp. It demonstrates a core exoproteome with conserved functions exists in the Leishmaniinae lineage. The bioinformatic characterization suggests thatL. passimexoproteome may interact with the host and its microbiota as well as their metabolites. Deletion of genes encoding two secretome proteins revealed that an aspartyl protease but not chitinase affects the development ofL. passimunder the culture condition and is necessary for the efficient infection in the honey bee gut. Our results demonstrate that the exoproteome represents a resource to uncover the mechanisms of trypanosomatid parasites to infect the insect host by interacting with the gut environment.
Evidence for subjective values guiding cognitive integration of gravity in a free speed manifold pointing task
Authors: Devemy Arthur , Papaxanthis Charalambos , da Silva Pontes Lucieny , Pozzo Thierry , Hilt Pauline M.
Published: January 2023

Studies of regularities in human movement control have led to the idea that our brains incorporate generic motor laws that guide our behaviors and thus these regularities. Among these, it has been argued that a generic internal model of gravity minimizes the body’s energy expenditure during actions performed in the vertical plane. According to this hypothesis, the energy criterion would represent the factor dominating motor planning. However, a growing body of experimental evidence indicates the presence of significant individual sensorimotor differences that suggest the use of various motor decision criteria.

We asked 41 voluntary participants to perform a free speed manifold pointing task (i.e., at three free different speeds and toward non-salient targets), in the vertical plane designed to avoid situation-specific responses and favor the expression of singularities. We found that temporal parameters (duration of motion and vigor) were idiosyncratic and not affected by mechanical effects induced by changes in velocity and gravitational force (i.e., assistive or resistive forces). Upward motions had a shorter time to reach maximum velocity than downward motions confirming the presence of asymmetric movement timing. Finally, synchronization of up-down movements was not correlated with energy minimization, indicating that movements performed in the vertical plane do not rely exclusively on a standard representation of gravity reducing effort. Rather, we concluded that individual values and the subjective rewards associated with each of these values could influence the planning of movements executed along the vertical plane as well as the cognitive integration of the gravitational force field.
Charting the Heterogeneity of Colorectal Cancer Consensus Molecular Subtypes using Spatial Transcriptomics
Authors: Valdeolivas Alberto , Amberg Bettina , Giroud Nicolas , Richardson Marion , Gálvez Eric J.C. , Badillo Solveig , Julien-Laferrière Alice , Turos Demeter , von Voithenberg Lena Voith , Wells Isabelle , Lo Amy A. , Yángüez Emilio , Das Thakur Meghna , Bscheider Michael , Sultan Marc , Kumpesa Nadine , Jacobsen Björn , Bergauer Tobias , Saez-Rodriguez Julio , Rottenberg Sven , Schwalie Petra C. , Hahn Kerstin
Published: January 2023

The heterogeneity of colorectal cancer (CRC) contributes to substantial differences in patient response to standard therapies. The consensus molecular subtypes (CMS) of CRC is the most widely-used gene expression-based classification and has contributed to a better understanding of disease heterogeneity and prognosis. Nevertheless, CMS intratumoral heterogeneity restricts its clinical application, stressing the necessity of further characterizing the composition and architecture of CRC. Here, we used Spatial Transcriptomics (ST) in combination with single-cell RNA sequencing (scRNA-seq) to decipher the spatially resolved cellular and molecular composition of CRC. In addition to mapping the intratumoral heterogeneity of CMS and their microenvironment, we identified cell communication events in the tumor-stroma interface of CMS2 carcinomas. This includes tumor growth-inhibiting as well as -activating signatures, such as the potential regulation of the ETV4 transcriptional activity by DCN or the PLAU-PLAUR ligand-receptor interaction. Our data show the power of ST to bring the CMS-based classification of CRC to another level and thereby gain useful molecular insights for personalized therapy.
Visual short-term memory related EEG components in a virtual reality setup
Authors: Klotzsche Felix , Gaebler Michael , Villringer Arno , Sommer Werner , Nikulin Vadim , Ohl Sven
Published: January 2023

Virtual reality (VR) offers a powerful tool for investigating cognitive processes, as it allows researchers to gauge behaviors and mental states in complex, yet highly controlled, scenarios. The use of VR head-mounted displays in combination with physiological measures such as EEG presents new challenges and raises the question whether established findings also generalize to a VR setup. Here, we used a VR headset to assess the spatial constraints underlying two well-established EEG correlates of visual short-term memory: the amplitude of the contralateral delay activity (CDA) and the lateralization of induced alpha power during memory retention. We tested observers’ visual memory in a delayed match-to-sample task with bilateral stimulus arrays of either two or four items while varying the horizontal eccentricity of the memory arrays (4, 9, or 14 degrees of visual angle). The CDA amplitude differed between high and low memory load at the two smaller eccentricities, but not at the largest eccentricity. Neither memory load nor eccentricity significantly influenced the observed alpha lateralization. We further fitted time-resolved spatial filters to decode memory load from the event-related potential as well as from its time-frequency decomposition. Classification performance during the retention interval was above chance level for both approaches and did not vary significantly across eccentricities. We conclude that commercial VR hardware can be utilized to study the CDA and lateralized alpha power, and we provide caveats for future studies targeting these EEG markers of visual memory in a VR setup.

Impact statement

Combining EEG with virtual reality, we studied how the eccentricity of a memory array during encoding affects well-known neural markers of visual short-term memory. We reveal that the previously reported occurrence of these EEG components during visual memory retention can be replicated in such a setup. These EEG markers were differently affected by eccentricity, hence providing valuable constraints for future experimental designs.
Mis-spliced transcripts generatede novoproteins in TDP-43-related ALS/FTD
Authors: Seddighi Sahba , Qi Yue A. , Brown Anna-Leigh , Wilkins Oscar G. , Bereda Colleen , Belair Cedric , Zhang Yongjie , Prudencio Mercedes , Keuss Matthew J , Khandeshi Aditya , Pickles Sarah , Hill Sarah E. , Hawrot James , Ramos Daniel M. , Yuan Hebao , Roberts Jessica , Sacramento Erika Kelmer , Shah Syed I. , Nalls Mike A. , Colon-Mercado Jenn , Reyes Joel F. , Ryan Veronica H. , Nelson Matthew P. , Cook Casey , Li Ziyi , Screven Laurel , Kwan Justin Y , Shantaraman Anantharaman , Ping Lingyan , Koike Yuka , Oskarsson Björn , Staff Nathan , Duong Duc M. , Ahmed Aisha , Secrier Maria , Ule Jerneg , Jacobson Steven , Rohrer Jonathan , Malaspina Andrea , Glass Jonathan D. , Ori Alessandro , Seyfried Nicholas T. , Maragkakis Manolis , Petrucelli Leonard , Fratta Pietro , Ward Michael E.
Published: January 2023

Functional loss of TDP-43, an RNA-binding protein genetically and pathologically linked to ALS and FTD, leads to inclusion of cryptic exons in hundreds of transcripts during disease. Cryptic exons can promote degradation of affected transcripts, deleteriously altering cellular function through loss-of-function mechanisms. However, the possibility ofde novoprotein synthesis from cryptic exon transcripts has not been explored. Here, we show that mRNA transcripts harboring cryptic exons generatede novoproteins both in TDP-43 deficient cellular models and in disease. Using coordinated transcriptomic and proteomic studies of TDP-43 depleted iPSC-derived neurons, we identified numerous peptides that mapped to cryptic exons. Cryptic exons identified in iPSC models were highly predictive of cryptic exons expressed in brains of patients with TDP-43 proteinopathy, including cryptic transcripts that generatedde novoproteins. We discovered that inclusion of cryptic peptide sequences in proteins altered their interactions with other proteins, thereby likely altering their function. Finally, we showed that thesede novopeptides were present in CSF from patients with ALS. The demonstration of cryptic exon translation suggests new mechanisms for ALS pathophysiology downstream of TDP-43 dysfunction and may provide a strategy for novel biomarker development.

One Sentence Summary

Loss of TDP-43 function results in the expression ofde novoproteins from mis-spliced mRNA transcripts.
Anatomo-functional changes in neural substrates of cognitive memory in developmental amnesia: Insights from automated and manual MRI examinations
Authors: Chareyron Loïc J. , Chong W.K. Kling , Banks Tina , Burgess Neil , Saunders Richard C. , Vargha-Khadem Faraneh
Published: January 2023

Despite bilateral hippocampal damage dating to perinatal or early-childhood period, and severely-impaired episodic memory that unfolds in later childhood, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganise to rescue aspects of these critical cognitive memory processes after early injury.

We used voxel-based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects.

Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA-DG subregions and subicular complex was more than 40% while the atrophy of the uncus was moderate (−23%). Anatomo-functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance viz, intelligence, working memory, and verbal and visuospatial recall.

Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions, such that the greater the damage, the more likely it is that surrounding cortical areas will be recruited to rescue the putative functions of the damaged subregions. Our findings document for the first time not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage.
Cont-ID: Detection of samples cross-contamination in viral metagenomic data
Authors: Rollin Johan , Rong Wei , Massart Sébastien
Published: January 2023

Background

High Throughput sequencing (HTS) technologies completed by the bioinformatic analysis of the generated data are becoming an important detection technique for virus diagnostics. They have the potential to replace or complement the current PCR-based methods thanks to their improved inclusivity and analytical sensitivity, as well as their overall good repeatability and reproducibility. Cross-contamination is a well-known phenomenon in molecular diagnostics and corresponds to the exchange of genetic material between samples. Cross-contamination management was a key drawback during the development of PCR-based detection and is now adequately monitored in routine diagnostics. HTS technologies are facing similar difficulties due to their very high analytical sensitivity. As a single viral read could be detected in millions of sequencing reads, it is mandatory to fix a detection threshold that will be influenced by cross-contamination. Cross-contamination monitoring should therefore be a priority when detecting viruses by HTS technologies.

Results

We present Cont-ID, a bioinformatic tool designed to check for cross-contamination by analysing the relative abundance of virus sequencing reads identified in sequence metagenomic datasets and their duplication between samples. It can be applied when the samples in a sequencing batch have been processed in parallel in the laboratory and with at least one external alien control. Using 273 real datasets, including 68 virus species from different hosts (fruit tree, plant, human) and several library preparation protocols (Ribodepleted total RNA, small RNA and double stranded RNA), we demonstrated that Cont-ID classifies with high accuracy (91%) viral species detection into (true) infection or (cross) contamination. This classification raises confidence in the detection and facilitates the downstream interpretation and confirmation of the results by prioritising the virus detections that should be confirmed.

Conclusions

Cross-contamination between samples when detecting viruses using HTS can be monitored and highlighted by Cont-ID (provided an alien control is present). Cont-ID is based on a flexible methodology relying on the output of bioinformatics analyses of the sequencing reads and considering the contamination pattern specific to each batch of samples. The Cont-ID method is adaptable so that each laboratory can optimise it before its validation and routine use.
Basolateral amygdala circuits supporting negative emotional bias in a mouse model for depression
Authors: Bigot Mathilde , De Badts Claire-Hélène , Benchetrit Axel , Vicq Éléonore , Moigneu Carine , Meyrel Manon , Wagner Sébastien , Houenou Josselin , Lledo Pierre-Marie , Henry Chantal , Alonso Mariana
Published: January 2023

Negative emotional bias is an essential hallmark of depression reflected by negative shift in hedonic valence assignment to emotional stimuli. Pleasant cues become less attractive and unpleasant ones more aversive. Given the crucial role of amygdala in valence coding, we hypothesize that specific basolateral amygdala (BLA) circuits alterations might support negative emotional bias associated with depressive states.

Using a translational assay, we evaluate odor valence assignment in an animal model for depression chronically administered by corticosterone (CORT). We show spontaneous negative bias in depressive-like mice that attribute more negative valences for both attractive and aversive odors, mimicking thus the bias observed in depressed bipolar patients.

Combining CTB and rabies-based tracing withex vivomeasurements of neuronal activity and chemogenetics experiments, we find that the CORT treatment reduces BLA-to-nucleus accumbens (NAc) neuronal activity and increases BLA-to-central amygdala activity, circuits respectively known to be involved in positive and negative valence encoding. Alterations in presynaptic connectivity of BLA-projecting neurons accompany these activity shifts. Interestingly, inputs from the paraventricular thalamus nucleus (PVT) towards BLA-to-NAc neurons are reduced in CORT-treated mice. Finally, chemogenetically activating the BLA-to-NAc circuit attenuates the negative bias in CORT-treated mice as well as the depressive-like phenotype, similarly than Fluoxetine antidepressant treatment. Altogether, we demonstrate that depressive states are associated with negative emotional bias both in human and mice. This bias is supported by activity shifts of specific BLA circuits along with durable presynaptic connectivity changes, but it could be alleviated by antidepressant drug or activity manipulation of altered BLA circuit.
Eye movements track prioritized auditory features in selective attention to natural speech
Authors: Gehmacher Quirin , Schubert Juliane , Schmidt Fabian , Hartmann Thomas , Reisinger Patrick , Rösch Sebastian , Schwarz Konrad , Popov Tzvetan , Chait Maria , Weisz Nathan
Published: January 2023

Over the last decades, cognitive neuroscience has identified a distributed set of brain regions that are critical for attention - one of the key principles of adaptive behavior. A strong anatomical overlap with brain regions critical for oculomotor processes suggests a joint network for attention and eye movements. However, the role of this shared network in complex, naturalistic environments remains understudied. Here, we investigated eye movements in relation to (un)attended sentences of natural speech in simultaneously recorded eye tracking and magnetoencephalographic (MEG) data. Using temporal response functions (TRF), we show that eye gaze tracks acoustic features (envelope and acoustic onsets) of attended speech, a phenomenon we termedocular speech tracking. Ocular speech envelope tracking even differentiates a target from a distractor in a multi speaker context and is further related to intelligibility. Moreover, we provide evidence for its contribution to neural differences in speech processing, emphasizing the necessity to consider oculomotor activity in future research and in the interpretation of neural differences in auditory cognition. Our results extend previous findings of a joint network of attention and eye movement control as well as motor theories of speech. They provide valuable new directions for research into the neurobiological mechanisms of the phenomenon, its dependence on learning and plasticity, and its functional implications in social communication.
Identification of Candidate Mitochondrial Inheritance Determinants Using the Mammalian Cell-Free System
Authors: Zuidema Dalen , Jones Alexis , Song Won-Hee , Zigo Michal , Sutovsky Peter
Published: January 2023

The degradation of sperm-borne mitochondria after fertilization is a conserved event. This process known as post-fertilization sperm mitophagy, ensures exclusively maternal inheritance of the mitochondria-harbored mitochondrial DNA genome. This mitochondrial degradation is in part carried out by the ubiquitin-proteasome system. In mammals, ubiquitin-binding pro-autophagic receptors such as SQSTM1 and GABARAP have also been shown to contribute to sperm mitophagy. These systems work in concert to ensure the timely degradation of the sperm-borne mitochondria after fertilization. We hypothesize that other receptors, cofactors, and substrates are involved in post-fertilization mitophagy. Mass spectrometry was used in conjunction with a porcine cell-free system to identify other autophagic cofactors involved in post-fertilization sperm mitophagy. This porcine cell-free system is able to recapitulate early fertilization proteomic interactions. Altogether, 185 proteins were identified as statistically different between control and cell-free treated spermatozoa. Six of these proteins were further investigated, including MVP, PSMG2, PSMA3, FUNDC2, SAMM50, and BAG5. These proteins were phenotyped using porcinein vitrofertilization, cell imaging, proteomics, and the porcine cell-free system. The present data confirms the involvement of known mitophagy determinants in the regulation of mitochondrial inheritance and provides a master list of candidate mitophagy co-factors to validate in the future hypothesis-driven studies.
Compressed phenotypic screens for complex multicellular models and high-content assays
Authors: Mead Benjamin E. , Kummerlowe Conner , Liu Nuo , Kattan Walaa E. , Cheng Thomas , Cheah Jaime H. , Soule Christian K. , Peters Josh , Lowder Kristen E. , Blainey Paul C. , Hahn William C. , Cleary Brian , Bryson Bryan , Winter Peter S. , Raghavan Srivatsan , Shalek Alex K.
Published: January 2023

High-throughput phenotypic screens leveraging biochemical perturbations, high-content readouts, and complex multicellular models could advance therapeutic discovery yet remain constrained by limitations of scale. To address this, we establish a method for compressing screens by pooling perturbations followed by computational deconvolution. Conducting controlled benchmarks with a highly bioactive small molecule library and a high-content imaging readout, we demonstrate increased efficiency for compressed experimental designs compared to conventional approaches. To prove generalizability, we apply compressed screening to examine transcriptional responses of patient-derived pancreatic cancer organoids to a library of tumor-microenvironment (TME)-nominated recombinant protein ligands. Using single-cell RNA-seq as a readout, we uncover reproducible phenotypic shifts induced by ligands that correlate with clinical features in larger datasets and are distinct from reference signatures available in public databases. In sum, our approach enables phenotypic screens that interrogate complex multicellular models with rich phenotypic readouts to advance translatable drug discovery as well as basic biology.
Telomerase-independent survival leads to a mosaic of complex subtelomere rearrangements inChlamydomonas reinhardtii
Authors: Chaux Frédéric , Agier Nicolas , Garrido Clotilde , Fischer Gilles , Eberhard Stephan , Xu Zhou
Published: January 2023

Telomeres and subtelomeres, the genomic regions located at chromosome extremities, are essential for genome stability in eukaryotes. In the absence of the canonical maintenance mechanism provided by telomerase, telomere shortening induces genome instability. The landscape of the ensuing genome rearrangements is not accessible by short-read sequencing. Here, we leverage Oxford Nanopore Technologies long-read sequencing to survey the extensive repertoire of genome rearrangements in telomerase mutants of the model green microalgaChlamydomonas reinhardtii. In telomerase mutant strains grown for ∼700 generations, most chromosome extremities were capped by short telomere sequences that were either recruitedde novofrom other loci or maintained in a telomerase-independent manner. Other extremities did not end with telomeres but only with repeated subtelomeric sequences. The subtelomeric elements, including rDNA, were massively rearranged and involved in breakage-fusion-bridge cycles, translocations, recombinations and chromosome circularization. These events were established progressively over time and displayed heterogeneity at the subpopulation level. New telomere-capped extremities composed of sequences originating from more internal genomic regions were associated with high DNA methylation, suggesting thatde novoheterochromatin formation contributes to restore chromosome end stability inC. reinhardtii. The diversity of alternative strategies to maintain chromosome integrity and the variety of rearrangements found in telomerase mutants are remarkable and illustrate genome plasticity at short timescales.
Streamlined regulation of chloroplast development in the liverwort Marchantia polymorpha
Authors: Yelina Natasha E , Frangedakis Eftychios , Wang Zhemin , Schreier Tina B , Rever Jenna , Tomaselli Marta , Forestier Edith , Billakurthi Kumari , Ren Sibo , Bai Yahui , Stewart-Wood Julia , Haseloff Jim , Zhong Silin , Hibberd Julian M
Published: January 2023

Photosynthesis in eukaryotic cells takes place in chloroplasts that develop from undifferentiated plastids in response to light. Two families of transcription factors known as Golden2-like (GLK) and GATA regulate plant chloroplast development, and the MIR171-targeted SCARECROW-LIKE (SCL) GRAS transcription factors regulate chlorophyll biosynthesis. Additionally, the Elongated Hypocotyl 5 (HY5) transcription factor plays a critical role in photomorphogenesis. The extent to which these proteins carry out conserved roles in non-seed plants such as the liverworts is not known. Here we determine the degree of functional conservation of the GLK, GATA, SCL and HY5 proteins in controlling chloroplast development in the model liverwort Marchantia polymorpha. Our results indicate that GATA, SCL and HY5 have a minimal or undetectable role in chloroplast biogenesis but loss of GLK function leads to reduced chloroplast size, underdeveloped thylakoid membranes and lower chlorophyll accumulation. ChIP-seq and RNA-seq analyses revealed that GLK can directly regulate many photosynthetic and chloroplast development-related genes. But there is extensive divergence between its function in M. polymorpha and flowering plants. Collectively our findings suggest that the function of GATA as well as SCL in chloroplast development and the more specialised role of HY5 in photomorphogenesis, either evolved after the divergence of vascular plants from bryophytes, that were lost in M. polymorpha, or that functional redundancy is masking their roles. In contrast, and consistent with its presence in algae, GLK plays a conserved role in chloroplast biogenesis of liverworts and vascular plants.
Compressed Perturb-seq: highly efficient screens for regulatory circuits using random composite perturbations
Authors: Yao Douglas , Binan Loic , Bezney Jon , Simonton Brooke , Freedman Jahanara , Frangieh Chris J. , Dey Kushal , Geiger-Schuller Kathryn , Eraslan Basak , Gusev Alexander , Regev Aviv , Cleary Brian
Published: January 2023

Pooled CRISPR screens with single-cell RNA-seq readout (Perturb-seq) have emerged as a key technique in functional genomics, but are limited in scale by cost and combinatorial complexity. Here, we reimagine Perturb-seq’s design through the lens of algorithms applied to random, low-dimensional observations. We present compressed Perturb-seq, which measures multiple random perturbations per cell or multiple cells per droplet and computationally decompresses these measurements by leveraging the sparse structure of regulatory circuits. Applied to 598 genes in the immune response to bacterial lipopolysaccharide, compressed Perturb-seq achieves the same accuracy as conventional Perturb-seq at 4 to 20-fold reduced cost, with greater power to learn genetic interactions. We identify known and novel regulators of immune responses and uncover evolutionarily constrained genes with downstream targets enriched for immune disease heritability, including many missed by existing GWAS or trans-eQTL studies. Our framework enables new scales of interrogation for a foundational method in functional genomics.
Investigation on intergranular corrosion susceptibility of a nitrogen-containing austenitic stainless steel QN2109 by optimized DL-EPR tests
Authors: Wang Xiangyu , He Pei , Zhou Qinglong , Zhou Qingyuan , Cheng Manlang , Sun Yangting , Jiang Yiming , Jiang Laizhu , Li Jin
Published: January 2023

Purpose

The purpose of this study is to investigate the intergranular corrosion (IGC) susceptibility of a nitrogen-containing austenitic stainless steel QN2109. The intergranular corrosion (IGC) susceptibility of a nitrogen-containing austenitic stainless steel QN2109 was investigated.

Design/methodology/approach

The double-loop electrochemical potentiodynamic reactivation (DL-EPR) tests were carried out. Scanning electron microscopy and atomic force microscopy were used to characterize the microstructure.

Findings

The optimized test condition for QN2109 was 1 M H2SO4 + 0.01 M NH4SCN at 40°C. The nose temperature of the temperature–time–sensitization (TTS) curve of QN2109 plot was approximately 750°C. Moreover, the IGC susceptibility started to appear at approximately 120 min. The Cr-depletion zone of QN2109 was generated by the formation of M23C6 rather than by the addition of nitrogen. The depth–width ratio of the grain boundaries after the DL-EPR tests decreased as the aging temperature increased. The degree of Cr depletion and size of the Cr-depletion zone at the grain boundary were reflected by the degree of sensitization and depth–width ratio, respectively.

Originality/value

The optimized test condition for DL-EPR tests of a nitrogen-containing austenitic stainless steel QN2109 was investigated. The TTS curve of QN2109 was first plotted to avoid IGC failure. The morphology of the Cr-depletion zone was reflected by the depth–width ratio.
Food safety and convenience meals: consumers' actual and perceived behaviours – a mixed methods study
Authors: Lavelle Fiona , McKernan Claire , Murphy Blain , Dean Moira
Published: January 2023

Purpose

Foodborne disease remains a significant public health threat and cause for concern. Despite numerous studies indicating that the domestic kitchen is a high-risk area for foodborne illness, consumers believe it is low-risk. The type of food being prepared in the kitchen has drastically changed, with an increased use of convenience products, perceived low-risk products. Little is known about consumers' behaviours with convenience meals. Therefore, it is essential to understand actual and perceived food safety behaviours in their use.

Methodology

A mixed-methods approach using in-home observations and semi-structured interviews was undertaken with participants from the UK and the Republic of Ireland (N = 50). Observational data was summarized using descriptive statistics and an inductive thematic analysis was conducted to interpret the qualitative data.

Findings

In this study general food safety behaviours, such as handwashing, use-by date checking, as well as identifying obvious safety hazard were suboptimal. However, participants' convenience meal safety behaviours were as optimal as possible with the provided instructions. The qualitative data supported the participants' struggle with the provided on-packet instructions. They also displayed participants' uncertain perceptions around different products, for example if oven-products could be reheated multiple times, and varying levels of concern around meat and dairy products. Consumers urged for more detailed and clearer instructions with these products. Recommendations for producers are provided to enhance consumer experience with the use of the products as well as contributing towards ensuring consumer safety.

Originality/value

Mixed-methods approach investigating consumers' real and perceived food safety behaviours.
Numerical and experimental investigation for enhancing thermal performance of a concentric heat exchanger using different scenarios
Authors: Aytaç İpek , Badali Yosef , Tuncer Azim Doğuş
Published: January 2023

Purpose

Heat exchangers (HEs) which provide heat transfer and transfer energy through direct or indirect contact between fluids have an essential role in many processes as a part of various industries from pharmaceutical production to electronic devices. Using nanofluid as working fluid and integrating different types of turbulators could be used to upgrade the thermal effectiveness of HEs. Recently, to obtain more increment in thermal effectiveness, hybrid nanofluids are used that are prepared by mixing two or more various nanoparticles. The purpose of this experimental and numerical study is investigating different scenarios for improving the effectiveness of a concentric U-tube type HE.

Design/methodology/approach

In the numerical section of this study, different turbulator modifications, including circular and quarter circular rings, were modeled to determine the effect of adding turbulator on thermal performance. In addition, Al2O3/water and SiO2/water single and Al2O3–SiO2/water hybrid nanofluids were experimentally tested in an unmodified concentric U-tube HE in two different modes, including counter flow and parallel flow. Al2O3–SiO2/water hybrid nanofluid was prepared at 2% (wt./wt.) particle ratio and compared with Al2O3/water and SiO2/water single type nanofluids at same particle ratios and with distilled water.

Findings

Numerical modeling findings exhibited that integrating turbulators to the concentric tube type HE caused to raise in the effectiveness by improving heat transfer area. Also, experimental results indicated that using both hybrid and single type nanofluids notably upgraded the thermal performance of the concentric U-tube HE. Integrating turbulators cannot be an effective alternative in a concentric U-tube type HE with lower diameter because of raise in pressure drop. Numerically achieved findings exhibited that using quarter circular turbulators decreased pressure drop in comparison with circular turbulators. According to the experimental outcomes, using hybrid Al2O3–SiO2/water nanofluid leads to obtain more thermal performance in comparison with single type nanofluids. The highest increment in overall heat transfer coefficient of HE by using Al2O3–SiO2/water nanofluid achieved as 58.97% experimentally.

Originality/value

The overall outcomes of the current research exhibited the positive impacts of using hybrid nanofluid and integrating turbulators. In this empirical and numerical survey, numerical simulations were performed to specify the impact of applying different turbulators and hybrid nanofluid on the flow and thermal characteristics in a concentric U-tube HE. The achieved outcomes exhibited that using hybrid nanofluid can notably increase the thermal performance with negligible pressure drop in comparison with two different turbulator modifications.
Sustainable maintenance planning in the petroleum industry: an application of system dynamics approach
Authors: Hosseinzadeh Mahnaz , Samadi Foroushani Marzieh , Ghayem Hakim , Mehregan Mohammad Reza
Published: January 2023

Purpose

While the petroleum industry remains to be the main source of energy in the world, it is responsible for a large amount of resource consumption, environmental emission and safety issues. In this industry, most of the refinery equipment are running out of their designed life cycle, leading to many challenges regarding equipment reliability, products quality, organizations’ profitability, human resources safety and job satisfaction, and environmental pollution, which affects not only the human resources of the refinery but also the people who live in the vicinity. This study aims to model and simulate the maintenance system of an oil refinery to reduce the rotating equipment’s downtime while simultaneously considering the three pillars of sustainability.

Design/methodology/approach

Considering the complexity of the system and its inherent dynamism, System Dynamics (SD) approach is applied to model and simulate the maintenance system of an oil refinery, aiming at reducing equipment’s downtime considering the three pillars of sustainability simultaneously. As a case study, the maintenance system of rotating equipment in the Abadan oil refinery of Iran is investigated.

Findings

Individual policies are investigated and categorized into three main groups: economic, social and environmental. The dynamic nature of the system demonstrates that applying combinations of the policies would be more effective than performing individual ones or even a combination of all policies at the same time. The findings show that to manage the maintenance and reliability issues in complex industries, only operational level maintenance strategies would not be helpful; rather, a holistic strategic solution counting different suppliers or even the government policies supporting the operational level maintenance decisions would be effective.

Originality/value

This study is the first which brings the perspective of sustainable policy-making in the SD modeling of a complex maintenance system like that of the petroleum industry. The developed model considers economic, environmental and social objectives simultaneously. Besides, it reflects the role of different stakeholders in the system. Furthermore, the policy-making attempt is not limited to the operational level corrective and maintenance solutions; instead, a comprehensive, holistic view is applied.
Dysfunctional behaviour in university accounting schools: a tale of management control
Authors: Tucker Basil , Parker Lee D. , Scully Glennda E.M.
Published: January 2023

Purpose

The purpose of this inductive, exploratory study is to provide foundational insights into the role of management control in dealing with dysfunctional behaviour within accounting schools in changing environment of Australian universities.

Design/methodology/approach

Evidence is drawn from semi-structured interviews with 28 current or previous heads of school, research deans, deans of teaching and learning, school managers and human resource managers from 16 Australian universities and interpreted from the theoretical perspective of rational choice theory.

Findings

The findings suggest the incidence of a range of dysfunctional behaviours occurring in accounting schools. Even when such behaviours are limited in frequency, their consequences are nevertheless found to have far-ranging and potentially destructive change impacts for both individuals and the university. Formal management control systems designed to address such behaviours are perceived to be largely ineffective in identifying, managing, eliminating or even mitigating the consequences of such dysfunctionality. Instead, it is informal control processes that are preferred in dealing with dysfunctionality.

Originality/value

This study enhances our understanding of the role of management control in dealing with dysfunctional behaviour within university accounting schools, and points not only to the difference between the design and use of management controls but also to the implications of this disconnect between the underlying intent of control design and their actual use in the context of environments that are subject to significant change.
The “snowflakes” of modern society: a qualitative investigation of female university students' anxiety about adulting
Authors: Talbot Amelia , O'Reilly Michelle , Dogra Nisha
Published: January 2023

Purpose

The paper aims to explore the anxiety of university students. The authors note that the rhetoric of the snowflake is frequently invoked in lay discourse to characterise a generation of young people as overly sensitive. This misleading conceptualisation is potentially stigmatising.

Design/methodology/approach

Interviews were conducted with tweleve young women (18–25 years) about anxiety during their transition through university and into adulthood.

Findings

The authors identified three themes: (1) students in a modern world, (2) gendered demands and (3) anxiety of adulting. Analysis demonstrated numerous, transecting and discourse-informed anxieties about modern life.

Practical implications

University professionals may benefit from understanding the gendered dimensions of anxiety associated with transitions to adulthood, including the increased pressures to succeed and achieve.

Originality/value

The arguably pejorative label of “snowflake” could negatively impact the social progress made in recognising the importance of taking care of mental health and help-seeking. This is especially concerning for females, as they have higher prevalence of anxiety conditions than males.
Exploring the effects of SMEs’ platform-based digital connectivity on firm performance – the moderating role of environmental turbulence
Authors: Rajala Anni , Hautala-Kankaanpää Tuire
Published: January 2023

Purpose

Small- and medium-sized enterprises (SMEs) often operate in environments marked by high levels of turbulence. Such firms adopt digital technologies and platforms that provide access to external real-time information and establish digital connectivity between firms to remain competitive. This study aims to focus on SMEs’ downstream and upstream platform-based digital connectivity (PDC).

Design/methodology/approach

This study examines the effects of PDC on SMEs’ operational performance under conditions of environmental turbulence. The data was gathered from 192 SMEs operating in the manufacturing arena.

Findings

The results show that the adoption of PDC does not directly affect an SME’s operational performance. However, in highly turbulent environments, PDC can improve operational performance. The results indicate that the performance effects of PDC vary according to the level and type of environmental turbulence.

Research limitations/implications

This research offers insights into the relationship between PDC among SMEs and operational performance and encourages future research examining other possible conditional effects that could explain the contradictory results found in previous research.

Originality/value

This study contributes to the knowledge of supply-chain digitalization among SMEs and its performance effects in varying environmental conditions. Further, this study contributes to the prior research by focusing on the interorganizational aspects of digitalization in SMEs.
Review of recent trends in ultrasonic additive manufacturing: current challenges and future prospects
Authors: Ishfaq Kashif , Abas Zafar , Saravana Kumar M. , Mahmood Muhammad Arif
Published: January 2023

Purpose

This study aims to outline the current challenges in ultrasonic additive manufacturing (AM). AM has revolutionized manufacturing and offers possible solutions when conventional techniques reach technological boundaries. Ultrasonic additive manufacturing (UAM) uses mechanical vibrations to join similar or dissimilar metals in three-dimensional assemblies. This hybrid fabrication method got attention due to minimum scrap and near-net-shape products.

Design/methodology/approach

This paper reviews significant UAM areas in process parameters such as pressure force, amplitude, weld speed and temperature. These process parameters used in different studies by researchers are compared and presented in tabular form. UAM process improvements and understanding of microstructures have been reported. This review paper also enlightens current challenges in the UAM process, process improvement methods such as heat treatment methods, foil-to-foil overlap and sonotrode surface roughness to increase the bond quality of welded parts.

Findings

Results showed that UAM could solve various problems and produce net shape products. It is concluded that process parameters such as pressure, weld speed, amplitude and temperature greatly influence weld quality by UAM. Post-weld heat treatment methods have been recommended to optimize the mechanical strength of ultrasonically welded joints process parameters. It has been found that the tension force is vital for the deformation of the pre-machined structures and for the elongation of the foil during UAM bonding. It is recommended to critically investigate the mechanical properties of welded parts with standard test procedures.

Originality/value

This study compiles relevant research and findings in UAM. The recent progress in UAM is presented in terms of material type, process parameters and process improvement, along with key findings of the particular investigation. The original contribution of this paper is to identify the research gaps in the process parameters of ultrasonic consolidation.
Numerical investigations on mechanical properties of bio-inspired 3D printed geometries using multi-jet fusion process
Authors: Chand Ramesh , Sharma Vishal S. , Trehan Rajeev , Gupta Munish Kumar
Published: January 2023

Purpose

The purpose of this study is to find the best geometries among the cylindrical, enamel and honeycomb geometries based upon the mechanical properties (tensile test, compression test and shear test). Further this obtained geometry could be used to fabricate products like exoskeleton and its supporting members.

Design/methodology/approach

The present research focuses on the mechanical testing of cylindrical, enamel and honeycomb-shaped parts fabricated through multi-jet printing (MJP) process with a wall thickness of 0.26, 0.33, 0.4 and 0.66 mm. The polymer specimens (for tensile, compression and shear tests) were fabricated using a multi-jet fusion process. The experimental results were compared with the numerical modelling. Finally, the optimal geometry was obtained, and the influence of wall thicknesses on various mechanical properties (tensile, compression and shear) was studied.

Findings

In comparison to cylindrical, enamel structures the honeycomb structures required less time to fabricate and had lower tensile, compressive and shear strengths. The most efficient geometry for fully functional parts where tensile, compressive and shear forces are present during application – cylindrical geometry is preferred followed by enamel, and then honeycomb. It was found that as the wall thickness of various geometries was increased, their ability to withstand tensile, compressive and shear loads also enhanced. The enamel shape structure exhibits greater strain energy storage capacity than other shape structures for compressive loads, and the strength to resist the compressive load will be lower. In the case of cylindrical geometries for tensile loading, the resisting area toward the loading will be higher in comparison to honeycomb- and enamel-based structures. At the same time, the ability to store the stain energy is less. The results of the tensile, compression and shear load finite element analysis using ANSYS are in agreement with those of the experiments.

Originality/value

From the insight of literature review, it is found that a wide range of work is done on fused deposition modeling (FDM) process. But in comparison to FDM, the MJP provide the better dimensional accuracy and surface properties (Lee et al., 2020). Therefore, it is observed that past research works not incorporated the effect of wall thickness of the embedded geometries on mechanical properties of the part fabricated on MJP (Gibson, n.d.). Hence, in this work, effect of wall thickness on tensile, compression and shear strength is considered as the main factor for the honeycomb, enamel and cylindrical geometries.