bluuebunny/crossref_metadata_2025 huggingface dataset:
A deep learning approach for cancer diagnosis exclusively from raw sequencing fragments of bisulfite-treated plasma cell-free DNA
Authors: Liu Jilei , Shen Hongru , Hu Jiani , Shen Xilin , Zhang Chao , Yang Yichen , Yang Meng , Wang Wei , Li Yang , Zhang Qiang , Yang Jilong , Chen Kexin , Li Xiangchun
Published: August 2023

Early cancer diagnosis from bisulfite-treated cell-free DNA (cfDNA) fragments require tedious data analytical procedures. Here, we present a Deep-learning-based approach for Early Cancer Interception and DIAgnosis (DECIDIA) that can achieve accurate cancer diagnosis exclusively from bisulfite-treated cfDNA sequencing fragments. DECIDIA relies on feature representation learning of DNA fragments and weakly supervised learning for classification. We systematically evaluate the performance of DECIDIA for cancer diagnosis and cancer-type prediction on a curated dataset of 5389 samples that consist of colorectal cancer (CRC, n = 1574), hepatocellular cell carcinoma (HCC, n = 1181), lung cancer (n = 654) and non-cancer control (n=1980). DECIDIA achieves an area under the receiver operating curve (AUROC) of 0.980 (95% CI, 0.976-0.984) in ten-fold cross validation settings on the CRC dataset, outperforming benchmarked methods that are based on fragmentation profiles and methylation intensities. Noticeably, DECIDIA achieves an AUROC of 0.910 (95% CI, 0.896-0.924) on the externally independent HCC testing set although there was no HCC data used in model development. In the settings of cancer-type classification, we observed that DECIDIA achieves a micro-average AUROC of 0.963 (95% CI, 0.960-0.966) and an overall accuracy of 82.8% (95%CI, 81.8% - 83.9%). In addition, we distilled four sequence signatures from the raw sequencing reads that exhibited differential patterns in cancer versus control and among different cancer types. Our approach represents a new paradigm towards eliminating the tedious data analytical procedures for liquid biopsy that uses bisulfite-treated cfDNA methylome.
Waning of post-vaccination neutralizing antibody responses against SARS-CoV-2, a systematic literature review and meta-analysis
Authors: Jacobsen Henning , Sitaras Ioannis , Katzmarzyk Maeva , Cobos Jiménez Viviana , Naughton Robert , Higdon Melissa M. , Deloria Knoll Maria
Published: August 2023

Background

Mass COVID-19 vaccination and the continuous introduction of new viral variants of SARS-CoV-2, especially of Omicron subvariants, has resulted in an increase in the proportion of the population with hybrid immunity at various stages of waning protection. We systematically reviewed waning of post-vaccination neutralizing antibody titers in different immunological settings to investigate potential differences.

Methods

We searched for studies providing data for post-vaccination neutralizing antibody responses against SARS-CoV-2 in PubMed, bioRxiv, and medRxiv from Dec 15, 2021, to Jan 31, 2023, using keywords related to COVID-19, vaccination, and antibody neutralization. We used random effects meta-regression to estimate the average fold-reduction in post-vaccination neutralizing antibody titers against the Index strain or Omicron BA.1. from month 1 to month 6 post last dose, stratified by vaccination regimen (primary or booster) and infection-naïve vs hybrid-immune status.

Findings

In total, 26 studies reporting longitudinal post-vaccination neutralizing antibody titers were included. Neutralization titers against the Index variant were available from all studies for infection-naïve participants, and from nine for hybrid-immune participants. Against Omicron BA.1, nine and eight studies were available for infection-naïve and hybrid-immune cohorts, respectively. In infection-naïve cohorts, post-vaccination neutralization titers against the Index strain waned 5.1-fold (95% CI 3.4-7.8) from month 1 to month 6 following primary regimen and 3.8-fold (95% CI 2.4-5.9) following the booster. Titers against Omicron BA.1 waned 5.9-fold (95% CI 3.8-9.0) in infection-naïve, post-booster cohorts. In hybrid-immune, post-primary vaccination cohorts, titers waned 3.7-fold (95% CI 1.7-7.9) against the Index strain and 5.0-fold (95% CI 1.1-21.8) against Omicron BA.1.

Interpretation

No obvious differences in waning between post-primary or post-boost vaccination were observed for vaccines used widely to date, nor between infection-naïve and hybrid-immune participants. Titers against Omicron BA.1 may wane faster compared to Index titers, which may worsen for more recent Omicron sub-variants and should be monitored. Relatively small datasets limit the precision of our current analysis; further investigation is needed when more data become available. However, based on our current findings, striking differences in waning for the analyzed and future comparisons are unlikely.
The Extent of Edgetic Perturbations in the Human Interactome Caused by Population-Specific Mutations
Authors: Cui Hongzhu , Srinivasan Suhas , Gao Ziyang , Korkin Dmitry
Published: August 2023

Until recently, efforts in population genetics have been focused primarily on people of European ancestry. To attenuate the bias, global population studies, such as the 1,000 Genomes Project, have revealed differences in genetic variation across ethnic groups. How much of these differences would attribute to the population-specific traits? To answer this question, the mutation data must be linked with the functional outcomes. A new “edgotype” concept has been proposed that emphasizes the interaction-specific, “edgetic”, perturbations caused by mutations in the interacting proteins. In this work, we performed a systematicin-silicoedgetic profiling of ∼50,000 non-synonymous SNVs (nsSNVs) from 1,000 Genomes Project by leveraging our semi-supervised learning approach SNP-IN tool on a comprehensive set of over 10,000 protein interaction complexes. We interrogated functional roles of the variants and their impact on the human interactome and compared the results with the pathogenic variants disrupting PPIs in the same interactome. Our results demonstrated that a considerable number of nsSNVs from healthy populations could rewire the interactome. We also showed that the proteins enriched with the interaction-disrupting mutations were associated with diverse functions and had implications in a broad spectrum of diseases. Further analysis indicated that distinct gene edgetic profiles among major populations could shed light on the molecular mechanisms behind the population phenotypic variances. Finally, the network analysis revealed that the disease-associated modules surprisingly harbored a higher density of interaction-disrupting mutations from the healthy populations. The variation in the cumulative network damage within these modules could potentially account for the observed disparities in disease susceptibility, which are distinctly specific to certain populations. Our work demonstrates the feasibility of a large-scalein-silicoedgetic study and reveals insights into the orchestrated play of the population-specific mutations in the human interactome.
TMEM165 acts as a proton-activated Ca2+importer in lysosomes
Authors: Zajac Matthew , Mukherjee Sourajit , Anees Palapuravan , Oettinger Daphne , Henn Katharine , Srikumar Jainaha , Zou Junyi , Saminathan Anand , Krishnan Yamuna
Published: August 2023

Lysosomal calcium (Ca2+) release is critical to cell signaling and is mediated by well-known lysosomal Ca2+channels. Yet, how lysosomes refill their Ca2+remains hitherto undescribed. Here, from an RNAi screen, we identify an evolutionarily conserved gene,lci-1, that facilitates lysosomal Ca2+entry inC. elegansand in mammalian cells. Its human homolog TMEM165, previously designated as a Golgi-resident Ca2+/H+exchanger (CAX), has a minor lysosomal population of unknown function. Using genetics, lysosomal Ca2+imaging and electrophysiology, we show that TMEM165 acts as a proton-activated, lysosomalCa2+importer in lysosomes. Defects in lysosomal Ca2+channels cause several neurodegenerative diseases, and knowledge of lysosomal Ca2+importers may provide new avenues to explore the physiology of Ca2+channels.
Top-down attention shifts behavioral and neural event boundaries in narratives with overlapping event scripts
Authors: De Soares Alexandra , Kim Tony , Mugisho Franck , Zhu Elen , Lin Allison , Zheng Chen , Baldassano Christopher
Published: August 2023

Understanding and remembering the complex experiences of everyday life relies critically on prior schematic knowledge about how events in our world unfold over time. How does the brain construct event representations from a library of schematic scripts, and how does activating a specific script impact the way that events are segmented in time? We developed a novel set of 16 audio narratives, each of which combines one of four location-relevant event scripts (restaurant, airport, grocery store, lecture hall) with one of four socially-relevant event scripts (breakup, proposal, business deal, meet cute), and presented them to participants in an fMRI study and a separate online study. Responses in angular gyrus, parahippocampal gyrus, and subregions of medial prefrontal cortex (mPFC) were driven by both location and social script information, showing that these regions can track schematic sequences from multiple domains. For some stories participants were primed to attend to one of the two scripts, by training them to listen for and remember specific script-relevant episodic details. Activating a location-related event script shifted the timing of subjective event boundaries to align with script-relevant changes in the narratives, and this behavioral shift was mirrored in the timing of neural responses, with mPFC event boundaries (identified using a Hidden Markov Model) aligning to location-relevant rather than socially-relevant boundaries when participants were location primed. Our findings demonstrate that neural event dynamics are actively modulated by top-down goals, and provide new insight into how narrative event representations are constructed through the activation of temporally-structured prior knowledge.
A bacterial sialidase mediates early life colonization by a pioneering gut commensal
Authors: Buzun Ekaterina , Hsu Chia-Yun , Sejane Kristija , Oles Renee E. , Ayala Adriana Vasquez , Loomis Luke R. , Zhao Jiaqi , Rossitto Leigh-Ana , McGrosso Dominic , Gonzalez David J. , Bode Lars , Chu Hiutung
Published: August 2023

The early microbial colonization of the gastrointestinal tract can lead to long-term impacts in development and overall human health. Keystone species, includingBacteroides spp., play a crucial role in maintaining the structure, diversity, and function of the intestinal ecosystem. However, the process by which a defined and resilient community is curated and maintained during early life remains inadequately understood. Here, we show that a single sialidase, NanH, inBacteroides fragilismediates stable occupancy of the intestinal mucosa and regulates the commensal colonization program during the first weeks of life. This program is triggered by sialylated glycans, including those found in human milk oligosaccharides and intestinal mucus. After examining the dynamics between pioneer gutBacteroidesspecies in the murine gut, we discovered that NanH enables vertical transmission from dams to pups and promotesB. fragilisdominance during early life. Furthermore, we demonstrate that NanH facilitates commensal resilience and recovery after antibiotic treatment in a defined microbial community. Collectively, our study reveals a co-evolutionary mechanism between the host and the microbiota mediated through host-derived glycans to promote stable intestinal colonization.
CD20 is a mammalian odorant receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators
Authors: Jiang Hao-Ching , Park Sung Jin , Wang I-Hao , Bear Daniel M. , Nowlan Alexandra , Greer Paul L.
Published: August 2023

The mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian odorant receptor that recognizes compounds produced by mouse predators. While wild-type mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a novel CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival.
A strict requirement in proteasome substrates for spacing between ubiquitin tag and degradation initiation elements
Authors: Davis Caroline , Spaller B. L. , Choi Erin , Kurrasch Joseph , Chong Haemin , Elsasser Suzanne , Finley Daniel , Matouschek Andreas
Published: August 2023

Proteins are typically targeted to the proteasome for degradation through the attachment of ubiquitin chains and the proteasome initiates degradation at a disordered region within the target protein. Yet some proteins with ubiquitin chains and disordered regions escape degradation. Here we investigate how the position of the ubiquitin chain on the target protein relative to the disordered region modulates degradation and show that the distance between the two determines whether a protein is degraded efficiently. This distance depends on the type of the degradation tag and is likely a result of the separation on the proteasome between the receptor that binds the tag and the site that engages the disordered region.
Intrinsic Susceptibility Of The Left Vs Right Recurrent Laryngeal Nerve To Paralysis: A Systematic Review
Authors: Oswald Aaron , Pitman Michael J
Published: August 2023

Objective

Unilateral vocal fold paralysis (UVFP) occurs more commonly on the left than right, a difference historically attributed to greater left recurrent laryngeal nerve (RLN) length and its presence in the thorax with consequential increased exposure to injury. However, considering the importance of mRNA locally transcribed in the distal nerve after nerve injury, there may be other intrinsic neuromuscular reasons for this discrepancy. To investigate whether intrinsic neuromuscular issues influence laterality, this study investigates the rate of paralysis relative to side in idiopathic and short-term intubation cases, excluding cases due to identifiable disease and surgery.

Data Sources

Embase and PubMed database

Review Methods

A systematic literature search was performed to capture articles published up until May 2022. Articles were included if laterality and etiology of paralysis were reported. Demographic data was extracted for patients diagnosed with idiopathic paralysis or paralysis after intubation for procedures performed outside the head, neck, and thorax. Study design was collected from included articles.

Results

Twenty-one studies were included, from which 702 patients were drawn for analysis. Within the idiopathic group, 69.2% were left-sided. Within the post-intubation group, 67.9% were left-sided.

Conclusions

The available evidence indicates that left-sided paralysis is more common in patients with idiopathic or short-term intubation related UVFP. This suggests intrinsic neuromuscular differences contribute to the left RLN being more susceptible than the right to damage and dysfunction. Further study is needed to identify these differences, which may provide insights into the pathophysiology of RLN paralysis as well possible therapeutic options.
Global Approaches to Older Abuse Research in Institutional Care Settings: A Systematic Review
Authors: Agaliotis Maria , Morris Tracey , Katz Ilan , Greenfield David
Published: August 2023

Objective

Over the last two decades, authors have argued the rate of abuse among older adults in institutional settings has been underestimated due to challenges in defining and responding to the issue. The purpose of this systematic review is to provide an in-depth analysis of empirical studies examining methodologies measuring abuse of older people residing in a long-term institutional care facility (nursing homes, independent living and assisted living facilities), specifically staff-to-resident abuse.

Methods

Guided by PRISMA guidelines, 10 databases were searched from 2005 till July 2023. This review inclusion criteria were any type of abuse, as defined by the World Health Organization reported by staff and residents, family and relatives, and public anonymous registries. This article also includes a methodological critical assessment of studies which has not been conducted before. To direct the review, we use four guiding questions: a) what are the study characteristics? b) what are the methods and measurement tools that have been used? c) what has been the impact of methodology on the results? and d) what is the quality of these studies?

Results

In the last 18 years, 22 studies from eight counties undertook cross-sectional examinations of staff-to-resident abuse. The review identified a heterogeneity of definitions of abuse and variations with who reported abuse, measurement tools and recall periods. We found the quality of studies varied significantly, with no consistency.

Discussion

These variations in study methodologies impacted the ability to synthesise the findings making it difficult to estimate a global prevalence rate of aged care abuse. From the analysis, we develop an Aged Care Abuse Research Checklist (ACARC) as a first step towards achieving a global standardized, evidence-based methodology for this field. Doing so will normalize processes within organizations and the community, allowing early interventions to change practices, reduce the risk of recurrence and improve resident quality of care and workplace cultures.

Systematic Review Registration Number

PROSPERO registry number: CRD42018055484,https://www.crd.york.ac.uk/PROSPERO.
Enhanced Deep Convolutional Neural Network for SARS-CoV-2 Variants Classification
Authors: Mwanga Mike J. , Obura Hesborn O. , Evans Mudibo , Awe Olaitan I.
Published: August 2023

High-throughput sequencing techniques and sequence analysis have enabled the taxonomic classification of pathogens present in clinical samples. Sequencing provides an unbiased identification and systematic classification of pathogens and this is generally achieved by comparing novel sequences to pre-existing annotated reference databases. However, this approach is limited by large-scale reference databases which require considerable computational resources and skills to compare against. Alternative robust methods such as machine learning are currently employed in genome sequence analysis and classification, and it can be applied in classifying SARS-CoV-2 variants, whose continued evolution has resulted in the emergence of multiple variants.

We developed a deep learning Convolutional Neural Networks-Long Short Term Memory (CNN-LSTM) model to classify dominant SARS-CoV-2 variants (omicron, delta, beta, gamma and alpha) based on gene sequences from the surface glycoprotein (spike gene). We trained and validated the model using > 26,000 SARS-CoV-2 sequences from the GISAID database. The model was evaluated using unseen 3,057 SARS-CoV-2 sequences. The model was compared to existing molecular epidemiology tool, nextclade.

Our model achieved an accuracy of 98.55% on training, 99.19% on the validation and 98.41% on the test dataset. Comparing the proposed model to nextclade, the model achieved significant accuracy in classifying SARS-CoV-2 variants from unseen data. Nextclade identified the presence of recombinant strains in the evaluation data, a mechanism that the proposed model did not detect.

This study provides an alternative approach to pre-existing methods employed in the classification of SARS-CoV-2 variants. Timely classification will enable effective monitoring and tracking of SARS-CoV-2 variants and inform public health policies in the control and management of the COVID-19 pandemic.
Structural basis of archaeal FttA-dependent transcription termination
Authors: Wang Chengyuan , Molodtsov Vadim , Sanders Travis J. , Marshall Craig J. , Firlar Emre , Kaelber Jason T. , Santangelo Thomas J. , Ebright Richard H.
Published: August 2023

The ribonuclease FttA mediates factor-dependent transcription termination in archaea1–3. Here, we report the structure of aThermococcus kodakarensistranscription pre-termination complex comprising FttA, Spt4, Spt5, and a transcription elongation complex (TEC). The structure shows that FttA interacts with the TEC in a manner that enables RNA to proceed directly from the TEC RNA-exit channel to the FttA catalytic center and that enables endonucleolytic cleavage of RNA by FttA, followed by 5’→3’ exonucleolytic cleavage of RNA by FttA and concomitant 5’→3’ translocation of FttA on RNA, to apply mechanical force to the TEC and trigger termination. The structure further reveals that Spt5 bridges FttA and the TEC, explaining how Spt5 stimulates FttA-dependent termination. The results reveal functional analogy between bacterial and archaeal factor-dependent termination, reveal functional homology between archaeal and eukaryotic factor-dependent termination, and reveal fundamental mechanistic similarities in factor-dependent termination in the three domains of life: bacterial, archaeal, and eukaryotic.

One sentence summary

Cryo-EM reveals the structure of the archaeal FttA pre-termination complex
Concurrent D-loop cleavage by Mus81 and Yen1 yields half-crossover precursors
Authors: Carreira Raquel , Aguado F. Javier , Crugeiras Maria , Sebesta Marek , Krejci Lumir , Blanco Miguel G.
Published: August 2023

Homologous recombination involves the formation of branched DNA molecules that may interfere with chromosome segregation. To resolve these persistent joint molecules, cells rely on the activation of structure-selective endonucleases (SSEs) during the late stages of the cell cycle. However, the premature activation of SSEs compromises genome integrity, due to untimely processing of replication/recombination intermediates. Here, we employed a biochemical approach to demonstrate that the budding yeast SSEs Mus81 and Yen1 possess the ability to cleave the central recombination intermediate known as the displacement loop or D-loop. Moreover, we confirm that, consistently with previous genetic data, the simultaneous action of Mus81 and Yen1, followed by ligation, is sufficient to recreate the formation of a half-crossover precursorin vitro.Our results provide not only mechanistic explanation for the formation of a half-crossover, but also highlight the critical importance for precise regulation of these SSEs to prevent chromosomal rearrangements.
BRAT1 associates with INTS11/INTS9 heterodimer to regulate key neurodevelopmental genes
Authors: Dokaneheifard Sadat , Gomes Dos Santos Helena , Valencia Monica Guiselle , Arigela Harikumar , Shiekhattar Ramin
Published: August 2023

Integrator is a multi-subunits protein complex involved in regulation of gene expression. Several Integrator subunits have been found to be mutated in human neurodevelopmental disorders, suggesting a key role for the complex in the development of nervous system.BRAT1is similarly linked with neurodegenerative diseases and neurodevelopmental disorders such as rigidity and multifocal-seizure syndrome. Here, we show that INTS11 and INTS9 subunits of Integrator complex interact with BRAT1 and form a trimeric complex in human HEK293T cells as well as in pluripotent human embryonal carcinoma cell line (NT2). We find thatBRAT1depletion disrupts the differentiation of NT2 cells into astrocytes and neural cells. Loss ofBRAT1results in inability to activate many neuronal genes that are targets of REST, a neuronal silencer. We identified BRAT1 and INTS11 co-occupying the promoter region of these genes and pinpoint a role for BRAT1 in recruiting INTS11 to their promoters. Disease-causing mutations inBRAT1diminish its association with INTS11/INTS9, linking the manifestation of disease phenotypes with a defect in transcriptional activation of key neuronal genes by BRAT1/INTS11/INTS9 complex.

Highlights

Integrator subunits INTS9 and INTS11 tightly interact with BRAT1

Depletion ofBRAT1causes a dramatic delay in human neural differentiation

BRAT1 and INTS11 module targets the promoters of neural marker genes and co-regulates their expression. The recruitment of INTS11 to these sites is BRAT1-dependent.

Pathogenic E522K mutation inBRAT1disrupts its interaction with INTS11/INTS9 heterodimer.
Bacterial Shedu immune nucleases share a common enzymatic core regulated by diverse sensor domains
Authors: Gu Yajie , Li Huan , Deep Amar , Enustun Eray , Zhang Dapeng , Corbett Kevin D.
Published: August 2023

Prokaryotes encode diverse anti-bacteriophage immune systems, including the single-protein Shedu nuclease. Here we reveal the structural basis for activation ofBacillus cereusShedu. In the inactive homotetramer, a key catalytic residue in Shedu’s nuclease domain is sequestered away from the catalytic site. Activation involves a conformational change that completes the active site and promotes assembly of a homo-octamer for coordinated double-strand DNA cleavage. Removal of Shedu’s N-terminal domain ectopically activates the enzyme, suggesting that this domain allosterically inhibits Shedu in the absence of infection. Bioinformatic analysis of nearly 8,000 Shedu homologs reveals remarkable diversity in their N-terminal regulatory domains: we identify 79 domain families falling into eight functional classes, including diverse nucleic acid binding, enzymatic, and other domains. Together, these data reveal Shedu as a broad family of immune nucleases with a common nuclease core regulated by diverse N-terminal domains that likely respond to a range of infection-related signals.
Microbiome Analysis of the Eastern Oyster As a Function of Ploidy and Seasons
Authors: Pathak Ashish , Marquez Mario , Stothard Paul , Chukwujindu Christian , Su Jian-Qiang , Zhou Yanyan , Zhou Xin-Yuan , Jagoe Charles H. , Chauhan Ashvini
Published: August 2023

Shellfish, such as the eastern oysters (Crassostrea virginica) are not only valued as seafood but also for the ecosystem services they provide, including improving water quality and reducing eutrophication. Excess N causes eutrophication, harmful algal blooms, fish kills and overall decline of estuarine ecosystems resulting in economic losses. Oyster reefs sequester N and enhance denitrification processes, however, information on the N cycling oyster microbiome is scarce with most studies focusing on random grab samples or on pathogens, such asVibrio spp. Further, triploid oysters are often used for aquaculture, as they grow faster than diploids, but there is little information on potential microbiome differences with ploidy. To address these knowledge gaps, diploid and triploid farmed oysters were collected at monthly intervals over one year and analyzed using a coupled approach encompassing shotgun metagenomics and quantitative microbial elemental cycling (QMEC) qPCR assays. Overall, the genusPsychrobacterdominated the core microbiome across all samples, regardless of season or ploidy, followed bySynechococcus,Pseudomonas,PseudoalteromonasandClostridium.Psychrobacterabundances increased significantly in the colder months; the same trend was also observed in the alpha and beta diversity. However, warmer months had increased bacterial diversity relative to colder months. Gene functional profiles were similar among seasons and ploidy, with respiration and metabolism of carbohydrates, RNA, and proteins as dominant functions. There were strong positive correlations between abundance of the “core” microbiome taxa and gene functions associated with central metabolism, DNA and carbohydrate metabolism, strongly suggesting the functional role ofPsychrobacterin the microbiome. Metagenome assembly was performed to characterize dominant species, followed by phylogenetic analysis of select MAGs (metagenome-assembled genomes), further supporting the presence of multiplePsychrobacterspp. Sequence-based identification of denitrification genes in thePyschrobacterMAGs indicated the presence ofnorB,narH,narI,nirK, andnorB. QMEC analysis indicated C and N cycling genes were most abundant, with no discernable patterns due to seasons or ploidy. Among N cycling genes, the nosZII clade was dominant, which is likely responsible for the eastern oysters potential for bioextraction and enhancing water quality via denitrification.
Structural basis for IL-33 recognition and its antagonism by the helminth effector protein HpARI
Authors: Jamwal Abhishek , Colomb Florent , McSorley Henry J. , Higgins Matthew K.
Published: August 2023

Interleukin 33 (IL-33) plays a significant role in inflammation, allergy, and host defence against parasitic helminths. The model gastrointestinal nematodeHeligmosomoides polygyrus bakeri(Hp) secretes the Alarmin Release Inhibitor (HpARI), a potent effector protein which suppresses protective immune responses and asthma in its host by inhibiting IL-33 signalling. Here we reveal the structure of HpARI bound to mouse IL-33. HpARI contains three CCP-like domains, and we show that it contacts IL-33 primarily through the second and third of these. A large loop which emerges from CCP3 directly contacts IL-33 and structural comparison shows that this overlaps with the binding site on IL-33 for its receptor, ST2, preventing formation of a signalling complex. Truncations of HpARI which lack the large loop from CCP3 are not able to block IL-33-mediated signalling in a cell-based assay and in anin vivomodel of asthma. This shows that direct competition between HpARI and ST2 is responsible for suppression of IL-33-dependent responses. This first structure of IL-33 bound to a pathogen-based inhibitor will guide future approaches to design therapeutics blocking IL-33-mediated allergic and inflammatory conditions.
Foxg1bimodally tunesL1-mRNA and -DNA dynamics in the developing murine neocortex
Authors: Liuzzi Gabriele , Mallamaci Antonello
Published: August 2023

Foxg1masters telencephalic development via a pleiotropic control of its articulation.L1is a large retrotransposon family expressed within CNS and suggested to contribute to its genomic plasticity. Foxg1 represses gene transcription, andL1elements share putative Foxg1 binding motifs, suggesting the former might limit telencephalic expression (and activity) of the latter. We tested such prediction, in vivo as well as in engineered primary neural cultures, by loss- and gain-of-function approaches. We showed thatFoxg1-dependent, transcriptionalL1repression specifically occurs in neopallial neuronogenic progenitors and post-mitotic neurons, where it is supported by specific changes in theL1epigenetic landscape. Unexpectedly, we also found that Foxg1 physically interacts withL1-mRNA and positively impacts on neonatal neopalliumL1-DNA content, antagonizing the retrotranscription-suppressing activity exerted by Mov10 and Ddx39a helicases. To our knowledge,Foxg1is the first CNS patterning gene acting as a bimodal retrotransposon modulator, limiting and promotingL1transcription and amplification, respectively, within a specific domain of the developing mouse brain.
Mitigating teleworkers' perceived technological complexity and work strains through supportive team communication
Authors: Wahl Ingrid , Wolfgruber Daniel , Einwiller Sabine
Published: August 2023

Purpose

Teleworkers need to use information and communication technology (ICT) to communicate and collaborate with their team members, however, when new and complicated information systems should be used, this can lead to stress. Receiving adequate information and emotional support from team members could reduce the stress caused by technological complexity and subsequent work and occupational strains.

Design/methodology/approach

Participants (N = 400) teleworked at least half of their working hours and were employed in organizations with a minimum of 250 employees. Data from the online survey were analyzed using structural equation modeling.

Findings

Results demonstrate that aspects of informational and emotional communication contribute to perceived social support from team members, with emotional communication explaining more variance. Stress from technological complexity is mitigated by both supportive team communication and the extent of telework. Perceived stress from technological complexity, however, still increases work and occupational strains.

Practical implications

The findings emphasize the importance of supportive internal communication to foster a collaborative telework environment. Practitioners in internal communication need to encourage teleworkers to help each other with adequate information and provide also emotional support to overcome the negative effects of complex ICT.

Originality/value

The study shows that supportive communication among team members is important for teleworkers to reduce work and occupational strains, especially when facing difficulties with complex ICT.
A game theory-based analysis of merchants’ mobile payment adoption using hybrid SEM-neural network approach
Authors: Naysary Babak
Published: August 2023

Purpose

Driven by the evidence from the literature on the significance of mobile (m-)payment in economic growth and productivity and at the same time the relative dismal adoption of this service, the purpose of present paper is to elucidate the merchants’ m-payment adoption from the perspective of trust, drawing upon the game theory framework, in the Malaysian context.

Design/methodology/approach

An online survey consisting of 302 respondents was carried out to investigate the impact of trust and opportunism on merchants’ perceived trustworthiness using a two-staged structural equation modeling–neural network approach to determine the significance and relative importance of variables. This study also applies a game-theoretic approach to analyze the impact of trust on the relationship between merchants and m-payment service providers.

Findings

The results indicate a positive and statistically significant relationship between merchant trust, merchant opportunism and perceived trustworthiness, and a statistically significant negative relationship was found between m-payment provider opportunism and perceived trustworthiness. The findings from the prisoner’s dilemma two-player model indicate that the scenarios of mutual trust and mutual opportunism as paradigmatic of cooperation and defection produce the best and worse outcomes, respectively. An intriguing result was the positive impact of merchant opportunism on perceived trustworthiness, which indicates a very calculative orientation of merchants in m-payment contracting.

Originality/value

To the best of the authors’ knowledge, this is among the first attempts to propose a game theory approach to the interaction between merchants and m-payment providers under the framework of trust and opportunism. A game theory study in the context of m-payment adoption can contribute to the theoretical literature by providing insights into the decision-making processes of merchants. By incorporating trust and opportunism into the game theory model, we can gain a better understanding of how they affect the decision-making process and overall adoption rates. The conclusions and implications provide useful insights for managers of both m-payment platforms and merchants in this relational exchange. The results of the present research can provide insights into the factors that influence merchant decisions and guide them toward suitable partnerships for successful adoption and can guide authorities for policy interventions and supporting adoption efforts.
Pandemic lockdown as policy window for street-level innovation of health and substitution treatment services for people who use drugs
Authors: Nygaard-Christensen Maj , Houborg Esben
Published: August 2023

Purpose

This paper aims to examine policy innovation among street-level bureaucrats at low-threshold services to people who use drugs during the COVID-19 pandemic in Denmark.

Design/methodology/approach

This paper builds on two research projects conducted during the first pandemic lockdown in Denmark. The first is a case study of how COVID-19 impacted on people who use drugs (PWUD) and services for PWUD at the open drug scene in the neighborhood of Vesterbro in Copenhagen. The second is an ethnographic study of how users of services at the intersection of drug use and homelessness were impacted by lockdown.

Findings

Drawing on Kingdon’s “multiple policy streams” approach, this study shows how lockdown opened a “policy window” for innovating services to people who use drugs. This paper further shows how the pandemic crisis afforded street-level bureaucrats new possibilities for acting as “policy entrepreneurs” in a context where vertical bureaucratic barriers and horizontal cross-sectoral silos temporarily collapsed. Finally, the authors show how this had more lasting effects through the initiation of outreach opioid substitution treatment.

Social implications

In Denmark, the emergence of a “policy window” for street-level bureaucrats to act as street-level “entrepreneurs” occurred in a context of rapid government response to the pandemic. For crises to act as “policy windows” for innovation depends on strong, preexisting institutional landscapes.

Originality/value

This paper adds to existing literature on policy innovation during COVID-19 in two ways: methodologically by contributing an ethnographically grounded approach to studying policy innovation and theoretically by examining the conditions that allowed policy innovation to occur.
Asian Paints Company Limited: post-merger and acculturation challenges
Authors: Sinha Subhashis , Jain Nikunj Kumar , Singh Sachin , Nambudiri Ranjeet
Published: August 2023

Learning outcomes

The case has the following learning objectives: to understand the dilemmas that an emerging market MNC faces during pre-and post-acquisition scenarios; understand and appreciate the basic tensions that arise when two different companies with different cultural setups are integrated; understand the importance of creating a culture integration road map to leverage the synergies of two successful companies; and understand the role of leadership in leading and managing change.

Case overview/synopsis

Asian Paints Ltd. has been a market leader in the Indian paint market for over five decades (since 1967). Over the years, starting in 1978, the company has steadily spread its footprint in the international arena as well. As of 2017, Asian Paints was a leader in 10 overseas markets, one of the top 3 paint companies in the Middle East, the largest paint manufacturing company in South Asia, and served 60 markets across the world. The international business contributed to around 12% of the company’s group turnover. In line with its long-term vision and to consolidate its presence in emerging markets, the company acquired Causeway Paints, a leading paint company in Sri Lanka, in April 2017. Asian Paints had a presence in Sri Lanka since 1999. Mr. Jatin Upadhyay, International Business Unit Head for Asian Paints, had played significant roles in the past in such acquisitions and was well aware of the impending challenges that came with such acquisitions. How would the integration of the two distinct entities be made possible without losing the overarching objective? How would the transition be managed? How would the cultural transition take place? What and how would the role be handled by the General Manager (GM) of Causeway Lanka? How would the new organisational structure support the transition? The case illustrates the complex management challenges that arise when a leading enterprise from a different country (Asian Paints) acquires a leading company in a different country, in this case, Causeway Paints, Sri Lanka.

Complexity academic level

The target audience for this case study is the students pursuing a post-graduate programme in management or an executive post-graduate programme in management. The case can also be used for management development programmes for experienced participants who are interested in understanding the possible scenarios that may arise after an acquisition when managing an international subsidiary in a different cultural setting.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 6: Human Resource Management.
International best practices for e-waste take back and policy interventions for India
Authors: Sheoran Monika , Das Gupta Devashish
Published: August 2023

Purpose

India generates around two million tonnes of e-waste every year, and it is increasing at a very high rate of 30%. However, due to inefficient handling of infrastructure and limited number of collection centres along with the absence of proper incentive structure for producer and recyclers, 95% of e-waste reaches to unorganized sector for disposal. Consumers are not aware of the need of proper e-waste disposal and in absence of proper motivation and they are not inclined towards recycling process. Therefore, this paper aims to identify the best practices of e-waste take adopted all over the world to implement effective policy interventions for e-waste management in India and other emerging economies.

Design/methodology/approach

This paper has recommended preventive as well as curative policy interventions on the basis of best e-waste management practices of Germany, Italy and Japan; life cycle assessment of e-waste; and SWOT analysis of Indian electronic product industry.

Findings

Preventive measures include a deposit refund scheme wherein a consumer will be responsible for depositing a refundable fees during the purchase of the product. The amount should be arrived at keeping in mind cost involved in handling e-waste and ensure some motivation for the consumers to give back used product. To ensure proper tracking of the product, Radio frequency identification (RFID) tags can be used which will be activated at the time of sale of product and remain so until product reaches some designated recycling space or recycler and consumer is returned back his deposit fee. Subsidy to the producers and recyclers can also be provided by the government to further incentivize the whole process. An example of mobile phones has been used to understand the proposed deposit fees and associated cost structure. Curative measures to reduce the generation of e-waste in long run for managing the discussed issue have also been proposed.

Originality/value

This study is an initiative for proposing and implementing best e-waste take back techniques in a developing economy like India by acquiring learnings from best/advanced economies in terms of e-waste take back.
Connecting the dots: linking empowering leadership, employee work passion, and flourishing-at-work
Authors: Peethambaran Meera , Naim Mohammad Faraz
Published: August 2023

Purpose

This paper aims to examine the relationship between empowering leadership and the holistic well-being construct, i.e. flourishing-at-work.

Design/methodology/approach

On the basis of an extensive review of literature and using conservation of resource (COR) theory and self-determination theory (SDT), this study proposes a conceptual framework with employee work passion (EWP) as a link connecting empowering leadership and flourishing-at-work.

Findings

Empowering leadership has the ability to enhance EWP and thereby increase the overall well-being of employees (flourishing). Moreover, the study demonstrates that EWP serves as a potential mechanism connecting empowering leadership and flourishing-at-work.

Research limitations/implications

Being a conceptual paper, the proposed framework lacks empirical validation.

Practical implications

Organizations should focus on leaders with empowering behaviours and strive towards increasing EWP.

Originality/value

To the best of the authors’ knowledge, this is the first study to propose the role of EWP as a possible conceptual link between empowering leadership and employee flourishing-at-work. This paper emphasizes the importance of flourishing-at-work in the current climate of rising mental tensions among employees, which leads to adverse organizational outcomes.
Enabling beneficial right for sovereign ṣukūk issuance in Indonesia: challenges and analysis
Authors: Armen Rio Erismen , Engku Ali Engku Rabiah Adawiah , Dewi Gemala
Published: August 2023

Purpose

This study aims to investigate beneficial right as a new legal concept and term accepted by the Indonesian legal system. The new concept was ratified to endorse government decision to use ṣukūk (as an Islamic financial instrument) in the financing of state budget deficit. Some legal issues emerged after the ratification such as the necessity to synchronize the beneficial right with other property rights in Indonesia and the disharmony between laws related to sovereign ṣukūk issuance.

Design/methodology/approach

The study uses a qualitative method with library study and interviews with relevant legal experts in Indonesia as the data collection techniques.

Findings

The findings show that the passage of Sovereign Ṣukūk Law 2008 that ratified beneficial right deemed as a concession point by the government to solve conflicts between legal restriction and employment of state-owned assets as the underlying asset of sovereign ṣukūk. The study deemed the necessity to improve the use of beneficial right in the Indonesian legal system which by the concept is not exercised for the issuance of sovereign ṣukūk only. There is the need to harmonize the administration of this right with other property rights in Indonesia.

Research limitations/implications

The scope of study will be limited to the Indonesian regulation related to the use of beneficial right concept in the issuance of sovereign ṣukūk in Indonesia. The regulation as mentioned will be in the form of statutes, presidential or ministerial regulations, and also opinions of Indonesian legal and sharīʿah scholars regarding the matter.

Originality/value

This study may explore significantly the use of beneficial right for the issuance of sovereign ṣukūk by the Government of Indonesia. Specifically, the study reveals and addresses the issues that are following the ratification of beneficial rights originated from the common law system into the Indonesian civil law system.
The effects of work-life balance on the well-being of older workers: same-same or same-different?
Authors: Haar Jarrod , Harris Candice , Myers Barbara
Published: August 2023

Purpose

The purpose of this paper is to extend the study of work-life balance (WLB) by exploring the influence of WLB amongst older workers. Theoretically, this study suggests that the psychological benefits of age on relationships between WLB and well-being might be stronger for those “younger” older workers than those working toward or beyond retirement age. This study tests a moderated mediation model whereby the effects of WLB on anxiety and depression (through job stress) are moderated by age.

Design/methodology/approach

Survey data from 512 New Zealand employees in three older age cohorts (55–59 years, 60–64 and 65+ years).

Findings

This study finds that WLB reduces job stress and leads to lower anxiety and depression. Job stress positively influences anxiety and depression and partially mediates the influence of WLB. Significant interaction effects are found by age, with the lower age cohort (55–59 years) reporting the strongest benefits from WLB and this effect reduces as employees get older but remains significant.

Social implications

Even when focusing on older workers, the findings show younger older workers elicit stronger benefits from WLB toward well-being, although all age groups find WLB beneficial.

Originality/value

This paper offers novel insights into the question of whether the importance of WLB for well-being differs among older workers.