bluuebunny/crossref_metadata_2025 huggingface dataset:
iPSC-based modeling of helicase deficiency reveals impaired cell proliferation and increased apoptosis after NK cell lineage commitment
Authors: Seo Seungmae , Patil Sagar L. , Ahn Yong-Oon , Armetta Jacqueline , Hegewisch-Solloa Everardo , Castillo Micah , Guilz Nicole C. , Patel Achchhe , Corneo Barbara , Borowiak Malgorzata , Gunaratne Preethi , Mace Emily M.
Published: September 2023

Cell proliferation is a ubiquitous process required for organismal development and homeostasis. However, individuals with partial loss-of-function variants in DNA replicative helicase components often present with immunodeficiency due to specific loss of natural killer (NK) cells. Such lineage-specific disease phenotypes raise questions on how the proliferation is regulated in cell type-specific manner. We aimed to understand NK cell-specific proliferative dynamics and vulnerability to impaired helicase function using iPSCs from individuals with NK cell deficiency (NKD) due to hereditary compound heterozygousGINS4variants. We observed and characterized heterogeneous cell populations that arise during the iPSC differentiation along with NK cells. While overall cell proliferation decreased with differentiation, early NK cell precursors showed a short burst of cell proliferation. GINS4 deficiency induced replication stress in these early NK cell precursors, which are poised for apoptosis, and ultimately recapitulate the NKD phenotype.
A direct experimental test of Ohno's hypothesis
Authors: Mihajlovic Ljiljana , Iyengar Bharat Ravi , Baier Florian , Barbier Içvara , Iwaszkiewicz Justyna , Zoete Vincent , Wagner Andreas , Schaerli Yolanda
Published: September 2023

Gene duplication drives evolution by providing raw material for proteins with novel functions. The oldest and historically most influential hypothesis about the evolutionary fate and potential of duplicated genes has been proposed by Susumu Ohno in 1970. This hypothesis essentially posits that gene duplication can help genes tolerate new mutations and thus facilitates the evolution of new phenotypes. Competing hypotheses argue that deleterious mutations will usually inactivate gene duplicates too rapidly for Ohno's hypothesis to work. Here, we provide a first direct experimental test of Ohno's hypothesis. Specifically, we evolved one or exactly two copies of a gene encoding a fluorescent protein in Escherichia coli through multiple rounds of mutagenesis and selection. We then analyzed the genotypic and phenotypic evolutionary dynamics of the evolving populations through high-throughput DNA sequencing, biochemical assays, and engineering of selected variants. In support of Ohno's hypothesis, populations carrying two gene copies displayed higher mutational robustness than those carrying a single gene copy. As a consequence, the double-copy populations experienced relaxed purifying selection, evolved higher phenotypic and genetic diversity, carried more mutations and accumulated combinations of key beneficial mutations earlier. However, their phenotypic evolution was not accelerated, possibly because one gene copy rapidly became inactivated by deleterious mutations. Our work provides an experimental platform to test models of evolution by gene duplication, and it supports alternatives to Ohno's hypothesis that point to the importance of gene dosage.
Towards label-free non-invasive autofluorescence multispectral imaging for melanoma diagnosis
Authors: Knab Aline , Anwer Ayad G. , Pedersen Bernadette , Handley Shannon , Marupally Abhilash Goud , Habibalahi Abbas , Goldys Ewa M.
Published: September 2023

This study focuses on the use of cellular autofluorescence which visualizes the cell metabolism by monitoring endogenous fluorophores including NAD(P)H and flavins. It explores the potential of multispectral imaging of native fluorophores in melanoma diagnostics using excitation wavelengths ranging from 340 nm to 510 nm and emission wavelengths above 391 nm. Cultured immortalized cells are utilized to compare the autofluorescent signatures of two melanoma cell lines to one fibroblast cell line. Feature analysis identifies the most significant and least correlated features for differentiating the cells. The investigation successfully applies this analysis to pre-processed, noise-removed images and original background-corrupted data. Furthermore, the applicability of distinguishing melanomas and healthy fibroblasts based on their autofluorescent characteristics is validated using patient cells with the same evaluation technique. Additionally, the study tentatively maps the detected features to underlying biological processes. This research demonstrates the potential of cellular autofluorescence as a promising tool for melanoma diagnostics.
Social administration of juvenile hormone to larvae increases body size and nutritional needs for pupation
Authors: Negroni Matteo A. , LeBoeuf Adria C.
Published: September 2023

Social insects often display extreme variation in body size and morphology within the same colony. In many species, adult morphology is socially regulated by workers during larval development. While larval nutrition may play a role in this regulation, it is often difficult to identify precisely what larvae receive from rearing workers, especially when larvae are fed through social regurgitation. Across insects, juvenile hormone is a major regulator of development. In the antCamponotus floridanusthis hormone is present in the socially regurgitated fluid of workers. We investigated the role the social transfer of juvenile hormone in the social regulation of development. To do this we administered an artificial regurgitate to larvae through a newly developed handfeeding method that was or was not supplemented with juvenile hormone. Orally administered juvenile hormone increased the nutritional needs of larvae, allowing them to reach a larger size at pupation. Instead of causing them to grow faster, the juvenile hormone treatment extended larval developmental time, allowing them to accumulate resources over a longer period. Handfeeding ant larvae with juvenile hormone resulted larger adult workers after metamorphosis, suggesting a role for social transferred juvenile hormone in the colony-level regulation of worker size over colony maturation.
Control of mitophagy initiation and progression by the TBK1 adaptors NAP1 and SINTBAD
Authors: Adriaenssens Elias , Nguyen Thanh Ngoc , Sawa-Makarska Justyna , Khuu Grace , Schuschnig Martina , Shoebridge Stephen , Watts Emily Maria , Csalyi Kitti Dora , Padman Benjamin Scott , Lazarou Michael , Martens Sascha
Published: September 2023

Mitophagy preserves overall mitochondrial fitness by selectively targeting damaged mitochondria for degradation. The regulatory mechanisms that prevent PINK1/Parkin-dependent mitophagy and other selective autophagy pathways from overreacting while ensuring swift progression once initiated are largely elusive. Here, we demonstrate how the TBK1 adaptors NAP1 and SINTBAD restrict the initiation of OPTN-driven mitophagy by competing with OPTN for TBK1. Conversely, they promote the progression of NDP52-driven mitophagy by recruiting TBK1 to NDP52 and stabilizing its interaction with FIP200. Notably, OPTN emerges as the primary recruiter of TBK1 during mitophagy initiation, which in return boosts NDP52-mediated mitophagy. Our results thus define NAP1 and SINTBAD as cargo receptor rheostats, elevating the threshold for mitophagy initiation by OPTN while promoting the progression of the pathway once set in motion by supporting NDP52. These findings shed light on the cellular strategy to prevent pathway hyperactivity while still ensuring efficient progression.
Assessing the role of mitonuclear interactions on mitochondrial function and organismal fitness in naturalDrosophilapopulations
Authors: Bettinazzi S , Liang J , Rodriguez E , Bonneau M , Holt R , Whitehead B , Dowling D.K , Lane N , Camus MF
Published: September 2023

Mitochondrial metabolism is regulated by a series of enzyme complexes, whose function depends on effective interactions between proteins and RNA encoded by the mitochondrial and nuclear genomes. These epistatic interactions are in turn highly sensitive to the environment. Many studies have found that mitochondrial haplotype frequencies of various taxa associate with latitude or altitude, leading to the hypothesis that mitochondrial genomes may respond to thermal selection and contribute to local adaptation. We used aDrosophila melanogasterpanel comprising native (coadapted) populations from the extremes of the Australian east-coast cline, and generated mitonuclear cybrid populations. Our results indicate a strong phenotypic impact of mitonuclear interactions in cybrid lines, involving an apparent trade-off between aerobic capacity and key fitness aspects such as reproduction, growth, and survival. Overall, our study shows that naturally-occurring mitonuclear disruptions can have a meaningful impact on phenotypes, potentially influencing future ecological adaptation and population persistence.
Dopamine enhances multisensory responses in the dorsomedial striatum
Authors: Sáez María , Alegre-Cortés Javier , Morgenstern Nicolás A. , García-Frigola Cristina , de la Torre-Martínez Roberto , Reig Ramón
Published: September 2023

The brain operates with simultaneous different sensory modalities in order to engage adaptive responses. However, the question of how (and where) multisensory information is integrated remains unanswered. In the dorsomedial striatum, single medium spiny neurons (MSNs) are excited by tactile and visual inputs; however, the mechanism which allows the integration of these responses and how they are shaped by dopamine is unknown.

Usingin vivooptopatch-clamp recordings, we study how dopamine modulates tactile, visual and simultaneous bimodal responses in identified MSNs and their spontaneous activity. Results show that dopamine enhances bimodal responses, specifically in direct pathway MSNs, through the acceleration of the visual responses. We provide anatomical and computational evidence suggesting that this relies on the disinhibition of direct MSNs by a cell-type-specific corticostriatal pathway. Altogether, ourin vivo,in silicoand tracing results propose a new mechanism underlying the synchronization of multimodal information mediated by dopamine.
Increased hippocampal epigenetic age in the Ts65Dn Mouse Model of Down Syndrome
Authors: Ravaioli Francesco , Stagni Fiorenza , Guidi Sandra , Pirazzini Chiara , Garagnani Paolo , Silvani Alessandro , Zoccoli Giovanna , Bartesaghi Renata , Bacalini Maria Giulia
Published: September 2023

Down syndrome (DS) is a segmental progeroid genetic disorder associated to multi-systemic precocious ageing phenotypes, which are particularly evident at the immune and nervous systems. Accordingly, people with DS show an increased biological age as measured by epigenetic clocks. Ts65Dn trisomic mouse, which harbors extra-numerary copies of Hsa21-syntenic regions, was shown to recapitulate several progeroid features of DS, but no biomarkers of age have been applied to it so far. Here we used a mouse specific epigenetic clock to measure epigenetic age of hippocampi from Ts65Dn and euploid mice at 20 weeks. Ts65Dn mice showed an increased hippocampal epigenetic age respect to controls, and the observed changes in DNA methylation partially recapitulated those observed in hippocampi from people with DS. Collectively, our results support the use of the Ts65Dn model to decipher the molecular mechanisms underlying the progeroid DS phenotypes.
Detection of reproducible liver cancer specific ligand-receptor signaling in blood
Authors: Safrastyan Aram , Wollny Damian
Published: September 2023

Cell-cell communication mediated by ligand-receptor interactions (LRI) is critical to coordinating diverse biological processes in homeostasis and disease. Lately, our understanding of these processes has greatly expanded through the inference of cellular communication, utilizing RNA extracted from bulk tissue or individual cells. Considering the challenge of obtaining tissue biopsies for these approaches, we considered the potential of studying cell-free RNA obtained from blood. To test the feasibility of this approach, we used the BulkSignalR algorithm across 295 cell-free RNA samples and compared the LRI profiles across multiple cancer types and healthy donors. Interestingly, we detected specific and reproducible LRIs particularly in the blood of liver cancer patients compared to healthy donors. We found an increase in the magnitude of hepatocyte interactions, notably hepatocyte autocrine interactions in liver cancer patients. Additionally, a robust panel of 30 liver cancer-specific LRIs presents a bridge linking liver cancer pathogenesis to discernible blood markers. In summary, our approach shows the plausibility of detecting liver LRIs in blood and builds upon the biological understanding of cell-free transcriptomes.
Arabidopsis thalianaphytocystatin 6 forms functional oligomer and amyloid fibril states
Authors: Santos Naiá P. , Brandstetter Hans , Dall Elfriede
Published: September 2023

Cystatins not only encode a high functional variability because of their ability to inhibit different classes of proteases but also because of their propensity to form oligomers and amyloid fibrils. Phytocystatins, essential regulators of protease activity in plants, specifically inhibit papain-like cysteine proteases (PLCPs) and legumains through two distinct cystatin domains. Mammalian cystatins can form amyloid fibrils, however, the potential for amyloid fibril formation of phytocystatins remains unknown. In this study, we demonstrate thatArabidopsis thalianaphytocystatin 6 (AtCYT6) exists as a mixture of monomeric, dimeric, and oligomeric forms in solution. Non-covalent oligomerization was facilitated by the N-terminal cystatin domain, while covalent dimerization occurred through disulfide bond formation in the interdomain linker. The non-covalent dimeric form of AtCYT6 retained activity against its target proteases, papain, and legumain, albeit with reduced inhibitory potency. Additionally, we observed the formation of amyloid fibrils by AtCYT6 under acidic pH conditions and upon heating. The amyloidogenic potential could be attributed to AtCYT6’s N-terminal domain (AtCYT6-NTD). Importantly, AtCYT6 amyloid fibrils harbored inhibitory activities against both papain and legumain. These findings shed light on the oligomerization and amyloidogenic behavior of AtCYT6, expanding our understanding of phytocystatin biology and its potential functional implications in plant protease regulation.
CDK8/19 Inhibition Attenuates G1 Arrest Induced by BCR-ABL Antagonists and Accelerates Death of Chronic Myelogenous Leukemia Cells
Authors: Khamidullina Alvina I. , Yastrebova Margarita A. , Bruter Alexandra V. , Nuzhina Julia V. , Vorobyeva Nadezhda E. , Khrustaleva Anastasia M. , Varlamova Ekaterina A. , Tyakht Alexander V. , Abramenko Yaroslav E. , Ivanova Ekaterina S. , Zamkova Maria A. , Li Jing , Lim Chang-Uk , Chen Mengqian , Broude Eugenia V. , Roninson Igor B. , Shtil Alexander A. , Tatarskiy Victor V.
Published: September 2023

Imatinib mesylate (IM) and other BCR-ABL tyrosine kinase inhibitors (BCR-ABLi) are the mainstay of chronic myelogenous leukemia (CML) treatment. However, activation of circumventing signaling pathways and quiescence may limit BCR-ABLi efficacy. CDK8/19 Mediator kinases have been implicated in the emergence of non-genetic drug resistance. Dissecting the effects of pharmacological CDK8/19 inhibition on CML survival in response to BCR-ABLi, we found that a selective, non-toxic CDK8/19 inhibitor (CDK8/19i) Senexin B (SenB) and other CDK8/19i sensitized K562 cells to different BCR-ABLi via attenuation of cell cycle arrest. In particular, SenB prevented IM-induced upregulation of genes that negatively regulate cell cycle progression. SenB also antagonized IM-activated p27Kip1elevation thereby diminishing the population of G1-arrested cells. After transient G1 arrest, cells treated with IM+SenB re-entered the S phase, where they were halted and underwent replicative stress. Consequently, the combination of IM and SenB intensified apoptotic cell death, measured by activation of caspase 9 and 3, subsequent cleavage of poly(ADPriboso)polymerase 1, positive Annexin V staining and increase of subG1 fraction. In contrast, IM-treated BCR-ABL-positive KU812 CML cells, which did not induce p27Kip1, readily died regardless of SenB treatment. Thus, CDK8/19i prevent the quiescence-mediated escape from BCR-ABLi-induced apoptosis, suggesting a strategy for avoiding the CML relapse.
Activin E is a TGFβ ligand that signals specifically through activin receptor-like kinase 7
Authors: Vestal Kylie A , Kattamuri Chandramohan , Koyiloth Muhasin , Ongaro Luisina , Howard James A , Deaton Aimee , Ticau Simina , Dubey Aditi , Bernard Daniel J , Thompson Thomas B
Published: September 2023

Activins are one of the three distinct subclasses within the greater Transforming Growth Factor β (TGFβ) superfamily. First discovered for their critical roles in reproductive biology, activins have since been shown to alter cellular differentiation and proliferation. At present, members of the activin subclass include activin A (ActA), ActB, ActC, ActE, and the more distant members myostatin and GDF11. While the biological roles and signaling mechanisms of most activins class members have been well-studied, the signaling potential of ActE has remained largely unknown. Here, we characterized the signaling capacity of homodimeric ActE. Molecular modeling of the ligand:receptor complexes showed that ActC and ActE shared high similarity in both the type I and type II receptor binding epitopes. ActE signaled specifically through ALK7, utilized the canonical activin type II receptors, ActRIIA and ActRIIB, and was resistant to the extracellular antagonists follistatin and WFIKKN. In mature murine adipocytes, ActE invoked a SMAD2/3 response via ALK7, similar to ActC. Collectively, our results establish ActE as an ALK7 ligand, thereby providing a link between genetic andin vivostudies of ActE as a regulator of adipose tissue.

Significance

Activin E is a homodimeric member of the TGFβ family belonging to the activin subclass. Currently, the signaling capacity of ActE is unknown due to a lack of reliable reagents to study the protein. Here, we demonstrate that ActE acts as a canonical TGFβ ligand that signals through SMAD2/3 in an ALK7-dependent manner, similar to ActC. ActE also utilizes the activin type II receptors, ActRIIA and ActRIIB, to signal and is unable to be antagonized by FS288 and WFIKKN2. This study shows that ActE is a signaling ligand and provides a connection between genetic andin vivostudies that links ActE to adiposity.
The species richness of theSalix viminalisrhizosphere at the Stebnyk tailings storages is dependent on supplementation from theSalicornia europaearhizosphere
Authors: Fetsiukh Anastasiia , Pall Taavi , Timmusk Salme
Published: September 2023

Manipulating the rhizosphere microbiome to enhance plant stress tolerance is an environmentally friendly technology and a renewable resource to restore degraded environments. Here we considered theSalicornia europaearhizosphere community, and the ability of the phytoremediation plantSalix viminalisto recruit its beneficial microbiome to mediate the pollution stress at the Stebnyk mine tailings storage. The tailings contain large amounts of brine salts and heavy metals that contaminate the ground water and surrounding areas, changing soil biogeochemistry and causing increased erosion. The species richness of the endophytic bacterial community ofS. viminalisroots was assessed based on observed OTUs, Shannon-InvSimpson, and evenness index. Our results show that biodiversity was decreased across the contamination zones and thatS. europaeasupplementation significantly increased the species richness. Our results also indicate that the number of dominating OTUs was not changed across zones in bothS. europaea-treated and untreated bacterial populations, and that the decrease in richness was mainly caused by the low abundance of OTUs.

The importance of engineering microbial communities that support the genetic diversity of degraded environments and the challenges with high throughput metabarcoding databases are discussed.
Dynein directs prophase centrosome migration to control the stem cell division axis in the developingC. elegansepidermis
Authors: Carvalho Cátia , Barbosa Daniel J. , Celestino Ricardo , Zanin Esther , Carvalho Ana Xavier , Gassmann Reto
Published: September 2023

The microtubule motor dynein is critical for the assembly and positioning of mitotic spindles. InC. elegans, these dynein functions have been extensively studied in the early embryo but remain poorly explored in other developmental contexts. Here we use a hypomorphic dynein mutant to investigate the motor’s contribution to asymmetric stem cell-like divisions in the larval epidermis. Live imaging of seam cell divisions that precede formation of the seam syncytium shows that mutant cells properly assemble but frequently mis-orient their spindle. Mis-oriented divisions misplace daughter cells from the seam cell row, generate anucleate compartments due to aberrant cytokinesis, and disrupt asymmetric cell fate inheritance. Consequently, the seam becomes disorganized and populated with extra cells that have lost seam identity, leading to fatal epidermal rupture. We show that dynein orients the spindle through the cortical GOA-1Gαi–LIN-5NuMApathway, which directs the migration of prophase centrosomes along the anterior–posterior axis. Spindle mis-orientation in the dynein mutant can be rescued by stretching cells, implying that dynein–dependent cortical cues and elongated cell shape jointly ensure correct asymmetric division of epithelial stem cells.
Electrostatic Interactions Dictate Bile Salt Hydrolase Substrate Preference
Authors: Malarney Kien P. , Chang Pamela V.
Published: September 2023

The human intestines are colonized by trillions of microbes, comprising the gut microbiota, which produce diverse small molecule metabolites and modify host metabolites, such as bile acids, that regulate host physiology. Biosynthesized in the liver, bile acids are conjugated with glycine or taurine and secreted into the intestines, where gut microbial bile salt hydrolases (BSHs) deconjugate the amino acid to produce unconjugated bile acids that serve as precursors for secondary bile acid metabolites. Among these include a recently discovered class of microbially-conjugated bile acids (MCBAs), wherein alternative amino acids are conjugated onto bile acids. To elucidate the metabolic potential of MCBAs, we performed detailed kinetic studies to investigate the preference of BSHs for host- and microbially-conjugated bile acids. We identified a BSH that exhibits positive cooperativity uniquely for MCBAs containing an aromatic sidechain. Further molecular modeling and phylogenetic analyses indicated that BSH preference for aromatic MCBAs is due to a substrate-specific cation-ρε interaction and is predicted to be widespread among human gut microbial BSHs.

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Soft selection affects introgression dynamics and the viability of populations experiencing intrusion of maladapted individuals
Authors: Reed Thomas Eric , Kane Adam , McGinnity Philip , O’Sullivan Ronan James
Published: September 2023

The deliberate release of captive-bred individuals, the accidental escape of domesticated strains, or the invasion of closely related conspecifics into wild populations can all lead to introgressive hybridisation, which poses a challenge for conservation and wildlife management. Rates of introgression and the magnitude of associated demographic impacts vary widely across ecological contexts. However, the reasons for this variation remain poorly understood. One rarely considered phenomenon in this context is soft selection, wherein relative trait values determine success in intraspecific competition for a limiting resource. Here we develop an eco-genetic model explicitly focussed on understanding the influence soft selection has on the eco-evolutionary dynamics of wild populations experiencing intrusion from foreign/domesticated individuals. While based on a generalised salmonine lifecycle, the model is applicable to any taxon that experiences incursion from locally maladapted genotypes, in addition to phenotype-dependent competition for a limiting resource (e.g., breeding sites, feeding territories). The effects of both acute and chronic intrusion depended strongly on the relative competitiveness of intruders versus locals. When intruders were competitively inferior, soft selection limited their reproductive success (ability to compete for limited spawning sites), which prevented strong introgression or population declines from occurring. In contrast, when intruders were competitively superior, this amplified introgression and led to increased maladaptation of the admixed population. This had negative consequences for population size and population viability. The results were sensitive to the intrusion level, the magnitude of reproductive excess, trait heritability, and the extent to which intruders were maladapted relative to locals. Our findings draw attention to under- appreciated interactions between soft selection and maladaptive hybridisation, which may be critical to determining the impact captive breeding programmes and domesticated escapees can have on otherwise self-sustaining wild populations.
The microcephaly geneASPMis required for the timely generation of human outer-radial glia progenitors by controlling mitotic spindle orientation
Authors: van Benthem Anja , Limame Ridha , Piumatti Matteo , Zaratin Maurine , Erkol Emir , Tanaka Daisuke H. , Herpoel Adèle , Bilheu Angéline , van Benthem Harmen , Rodriguez Laura Nebreda , Pirson Isabelle , Keymolen Kathelijn , Poovathingal Suresh , Ditkowska Martyna , Désir Julie , Passemard Sandrine , Abramowicz Marc , Ledent Catherine , Vanderhaeghen Pierre
Published: September 2023

Abnormal spindle-like, microcephaly-associated (ASPM) is the most commonly mutated gene in primary microcephaly (MCPH), characterized by reduced brain size and intellectual deficiency. The mechanisms underlying MCPH have remained unclear, asASPMdisruption leads to distinct phenotypes depending on the species studied. Here, we studied the impact ofASPMpathogenic mutations on human corticogenesis in organoid models. We found that at earliest stages of neurogenesis,ASPMmutant cortical progenitors, located at the apical surface of the neuroepithelium, display transient mitotic spindle randomization. The mutant progenitors then delaminate basally to adopt precociously the characteristics of outer radial glia cells (oRGC), a population of progenitors selectively amplified in human corticogenesis. Subsequently, cortical progenitors are depleted through decreased amplification and increased apoptosis. Thus,ASPMregulates the timely generation of oRGC by controlling mitotic spindle orientation, shedding light on how species-specific features of neurogenesis may confer vulnerability to neurodevelopmental diseases.
Calcineurin-dependent contributions to fitness in the opportunistic pathogenCandida glabrata
Authors: Pavesic Matthew W. , Gale Andrew N. , Nickels Timothy J. , Harrington Abigail A. , Bussey Maya , Cunningham Kyle W.
Published: September 2023

The protein phosphatase calcineurin is vital for virulence of the opportunistic fungal pathogenCandida glabrata. The host-induced stresses that activate calcineurin signaling are unknown, as are the targets of calcineurin relevant to virulence. To potentially shed light on these processes, millions of transposon insertion mutants throughout the genome ofC. glabratawere profileden massefor fitness defects in the presence of FK506, a specific inhibitor of calcineurin. 87 specific gene deficiencies depended on calcineurin signaling for full viabilityin vitroboth in wild type andpdr1Δnull strains lacking pleiotropic drug resistance. Three genes involved in cell wall biosynthesis (FKS1,DCW1,FLC1) possess co-essential paralogs whose expression depended on calcineurin and Crz1 in response to micafungin, a clinical antifungal that interferes with cell wall biogenesis. Interestingly, 80% of the FK506-sensitive mutants were deficient in different aspects of vesicular trafficking, such as endocytosis, exocytosis, sorting, and biogenesis of secretory proteins in the ER. In response to the experimental antifungal manogepix that blocks GPI-anchor biosynthesis in the ER, calcineurin signaling increased and strongly prevented cell death independent of Crz1, one of its major targets. Comparisons between manogepix, micafungin, and the ER-stressing tunicamycin reveal a correlation between the degree of calcineurin signaling and the degree of cell survival. These findings suggest that calcineurin plays major roles in mitigating stresses of vesicular trafficking. Such stresses may arise during host infection and in response antifungal therapies.
An efficient system matrix factorization method for scanning diffraction based strain tensor tomography
Authors: Henningsson Axel , Hall Stephen A.
Published: September 2023

Diffraction-based tomographic strain tensor reconstruction problems in which a strain tensor field is determined from measurements made in different crystallographic directions are considered in the context of sparse matrix algebra. Previous work has shown that the estimation of the crystal elastic strain field can be cast as a linear regression problem featuring a computationally involved assembly of a system matrix forward operator. This operator models the perturbation in diffraction signal as a function of spatial strain tensor state. The structure of this system matrix is analysed and a block-partitioned factorization is derived that reveals the forward operator as a sum of weighted scalar projection operators. Moreover, the factorization method is generalized for another diffraction model in which strain and orientation are coupled and can be reconstructed jointly. The proposed block-partitioned factorization method provides a bridge to classical absorption tomography and allows exploitation of standard tomographic ray-tracing libraries for implementation of the forward operator and its adjoint. Consequently, RAM-efficient, GPU-accelerated, on-the-fly strain/orientation tensor reconstruction is made possible, paving the way for higher spatial resolution studies of intragranular deformation.
A user-friendly plug-and-play cyclic olefin copolymer-based microfluidic chip for room-temperature, fixed-target serial crystallography
Authors: Liu Zhongrui , Gu Kevin K. , Shelby Megan L. , Gilbile Deepshika , Lyubimov Artem Y. , Russi Silvia , Cohen Aina E. , Narayanasamy Sankar Raju , Botha Sabine , Kupitz Christopher , Sierra Raymond G. , Poitevin Fredric , Gilardi Antonio , Lisova Stella , Coleman Matthew A. , Frank Matthias , Kuhl Tonya L.
Published: September 2023

Over the past two decades, serial X-ray crystallography has enabled the structure determination of a wide range of proteins. With the advent of X-ray free-electron lasers (XFELs), ever-smaller crystals have yielded high-resolution diffraction and structure determination. A crucial need to continue advancement is the efficient delivery of fragile and micrometre-sized crystals to the X-ray beam intersection. This paper presents an improved design of an all-polymer microfluidic `chip' for room-temperature fixed-target serial crystallography that can be tailored to broadly meet the needs of users at either synchrotron or XFEL light sources. The chips are designed to be customized around different types of crystals and offer users a friendly, quick, convenient, ultra-low-cost and robust sample-delivery platform. Compared with the previous iteration of the chip [Gilbile et al. (2021), Lab Chip, 21, 4831–4845], the new design eliminates cleanroom fabrication. It has a larger imaging area to volume, while maintaining crystal hydration stability for both in situ crystallization or direct crystal slurry loading. Crystals of two model proteins, lysozyme and thaumatin, were used to validate the effectiveness of the design at both synchrotron (lysozyme and thaumatin) and XFEL (lysozyme only) facilities, yielding complete data sets with resolutions of 1.42, 1.48 and 1.70 Å, respectively. Overall, the improved chip design, ease of fabrication and high modifiability create a powerful, all-around sample-delivery tool that structural biologists can quickly adopt, especially in cases of limited sample volume and small, fragile crystals.
UrbanClap: Market Place for On-Demand Services (A)
Authors: Abhishek  , Mukherjee Saral , Patra Yogita
Published: September 2023

UrbanClap was setup in October 2014 to address the opportunity of bringing the workforce from the unorganised sector into the mainstream using the power of technology. It was an on-demand marketplace for services available through a mobile app. In the initial years, UrbanClap, developed as horizontal marketplace, saw intense competition from existing and new players who were operating in the hyperlocal services space. It competed in the on-demand service marketplace by categorising its services into a lead generation business (where it connected customers with the service provider and charged a fee for matchmaking) and a fulfilment business (where UrbanClap took end-to-end responsibility for quality of service delivery). After three and half years of operations, the three co-founders wondered if it was time they moved out of lead generation and instead focussed on the fulfilment business.
CO2 pollution reduction: a tradeoff for fully fuzzy parameters in a megaproject optimization
Authors: Paryzad Behzad , Eshghi Kourosh
Published: September 2023

Purpose

This paper aims to conduct a fuzzy discrete time cost quality risk in the ambiguous mode CO2 tradeoff problem (FDTCQRP*TP) in a megaproject based on fuzzy ground.

Design/methodology/approach

A combinatorial evolutionary algorithm using Fuzzy Invasive Weed Optimization (FIWO) is used in the discrete form of the problem where the parameters are fully fuzzy multi-objective and provide a space incorporating all dimensions of the problem. Also, the fuzzy data and computations are used with the Chanas method selected for the computational analysis. Moreover, uncertainty is defined in FIWO. The presented FIWO simulation, its utility and superiority are tested on sample problems.

Findings

The reproduction, rearrangement and maintaining elite invasive weeds in FIWO can lead to a higher level of accuracy, convergence and strength for solving FDTCQRP*TP fuzzy rules and a risk ground in the ambiguous mode with the emphasis on the necessity of CO2 pollution reduction. The results reveal the effectiveness of the algorithm and its flexibility in the megaproject managers' decision making, convergence and accuracy regarding CO2 pollution reduction.

Originality/value

This paper offers a multi-objective fully fuzzy tradeoff in the ambiguous mode with the approach of CO2 pollution reduction.
Cause for change: lessons for Black liberation
Authors: Taylor Christopher Stuart
Published: September 2023

Purpose

Using the examples of Grenadian-born Jean Augustine, the first Black Member of Parliament in Canada, and Barbados' Prime Minister Mia Mottley, the piece argues that the ethos of the Emigrant Ambassador—the collective empowerment of Black feminism, liberation, and radicalism—ushered in a new era for change abroad and in Canada, as transnational and international change was driven by Black women from the West Indies.

Design/methodology/approach

The author used historical research and social science theoretical frameworks to formulate conclusions, lessons learnt and steps forward for current equity, diversity and inclusion (EDI) practitioners.

Findings

Black women born in the West Indies in the mid-twentieth century were the catalysts for social justice movements in the 2010 and 2020s. Many methods used for social change in the twentieth century are applicable in the 2020s and beyond.

Research limitations/implications

Research is focused on Canadian and West Indian relations but will have implications for those across the British Commonwealth.

Practical implications

Practitioners and students of EDI will have a new tool on how to approach and confront anti-Black racism, particularly after May 25, 2020.

Social implications

This article provides opportunities to support the dwindling efforts of anti-racism to support the lives of Black people across the Black Atlantic.

Originality/value

This is an original article built on previous scholarship of the author.
Applying methodological innovation to explore generativity development among collegiate leadership mentors
Authors: Hastings Lindsay J. , Sunderman Hannah M. , Sellon Addison
Published: September 2023

Purpose

Building upon a larger mixed-methods research agenda, the purpose of this research study was to explore the growth of generativity (i.e. care for the next generation) among college student leaders who mentor, answering the central question “What changes in generativity do college student leaders who mentor associate with their mentoring experience, and why?” and associated sub-question “How does generativity develop among college student leaders who mentor?”

Design/methodology/approach

Applying methodological innovation to a phenomenological design, semi-structured interviews were conducted and triangulated with pictorial degree-of-change graphs among 33 collegiate leadership mentors at a large Midwestern USA land-grant university.

Findings

The findings indicated that senior collegiate leadership mentors overwhelmingly acknowledged sustained generativity increases as a result of mentoring a younger student when given the tools, environment to process and time needed to develop trusting investment relationships. These increases in generativity were associated with changes in their understanding of generativity, the desire to pass on the knowledge given to them and growth in both mentor and mentee.

Originality/value

Findings from the current study advance mentoring research and practice by providing a deeper understanding of mentoring as a developmental intervention, informing antecedents of generativity and utilizing innovative qualitative methodological techniques.
Military CEOs and firm dividends and cash holdings
Authors: Le Nam Hoang , Li Zhe , Ramsey Megan
Published: September 2023

Purpose

The purpose of this study is to examine the relationships between chief executive officers (CEOs) with military service and firm dividend and cash holding decisions.

Design/methodology/approach

The authors use a sample of Standard and Poor's (S&P) 1500 firms in the USA over a sample period from 1999 to 2017 and a panel data approach, as well as instrumental variable (IV)analysis. The models control for firm characteristics as well as industry and year-fixed effects.

Findings

The results show CEOs with military service are associated with higher total payout and less cash. Higher dividends appear to drive the total payout result. When cash holdings are split into pure cash and short-term investments, the reduction in cash holdings is driven by a reduction in pure cash. The findings are more pronounced for powerful CEOs and CEOs with low labor mobility. Military CEOs are also associated with less risk, measured by stock return volatility and return on assets (ROA) volatility.

Originality/value

Overall, the results are consistent with military CEOs implementing conservative policies that reduce firm risk, curtailing the demand for precautionary cash and reducing the necessity to forego dividend payouts.
Perceived discrimination, adaptation and saudade among African migrants
Authors: Neto Félix
Published: September 2023

Purpose

For Lusophones, saudade is a common psychological experience related with the physical separation from loved ones and/or familiar locations. This study aims to examine the relationships between perception of discrimination, adaptation and saudade.

Design/methodology/approach

The sample consisted of 655 African migrants from Angola, Cape Verde, Guinea-Bissau and Mozambique living in Portugal with a mean age of 38 years. The average duration of stay in Portugal was 22 years.

Findings

Results indicated that length of residence impacted the difficulties experienced with saudade: respondents with longer lengths of stay in the society of settlement experienced less difficulty with saudade. As predicted, the results indicated that higher perceptions of discrimination and loneliness correlated positively with experienced saudade, while sociocultural adaptation correlated negatively with experienced saudade.

Originality/value

Path analysis was conducted to investigate mediation impacts of sociocultural adjustment and loneliness on the relationship between perception of discriminatory events and difficulty with saudade. This study suggests that sociocultural adaptation and loneliness partially mediated the relation between perception of discrimination and saudade. Notwithstanding the low level of perceived discrimination found in this African background sample, this antecedent plays a relevant role in the saudade experienced. This evidence may be useful in targeting programs to improve sociocultural adjustment and to reduce loneliness which may help to alleviate the difficulty with feeling saudade among African migrants.
Why retail firms commonly get only halfway through channel integration with online channels
Authors: Lee Philip Tin Yun , Hui Aki Pui Yi , Lui Richard Wing Cheung , Chau Michael
Published: September 2023

Purpose

This paper aims to examine why retail firms seldom achieve full integration of online and offline channels as prescribed in omni-channel literature. It examines the intermediate process of channel integration from an internal, operational perspective.

Design/methodology/approach

This study is composed of two parts. In the first part, the authors interviewed informants from nine firms that were engaged in channel integration. In the second part, the authors conducted case studies with three firms from the cosmetics and skincare industry against the backdrop of the COVID-19 pandemic to find evidence to support or negate the propositions made in the first part.

Findings

The first part identified six operational challenges to channel integration. The authors categorized these challenges into two groups: inter-channel communication and inter-channel competition. Inter-channel competition carries more weight at the latter stage of integration. The authors also identified two antecedents that affect the seriousness of these challenges: heterogeneity among channels in business operation and external competitive pressure. In the second part, the authors found that both inter-channel communication and inter-channel competition were improved because of the external competitive pressure exerted by the COVID-19 pandemic. However, the heterogeneity of offline channels against online channels in business operation is a double-edged sword.

Originality/value

The study identifies the changing effects of the challenges of channel integration and their antecedents in the midst of integration. The positive influence of a specific dimension of channel heterogeneity against other channels increases and then decreases along channel integration. The identification of the changing effects lays the foundation for a finer stage model of channel integration.
Understanding the relationship between teacher leadership and teacher well-being: the mediating roles of trust in leaders and teacher efficacy
Authors: Liu Peng , Chen Xiao Fei , Cheng Ya Xi , Xiao Shan Shan
Published: September 2023

Purpose

Teacher well-being has been a concern, but there has been a lack of research on how teacher leadership can contribute to teacher well-being in a high-accountability context and a hierarchical education system such as that of China, particularly through the meditating roles of trust in the leader and teacher efficacy. Therefore, the purpose of this study was to understand the relationship between teacher leadership and teacher well-being while exploring the mediating roles of trust in leaders and teacher efficacy in this relationship.

Design/methodology/approach

Using structural equation modeling (SEM) and bootstrap methods with valid answers from 1,144 teachers in 25 primary schools in 1 Chinese city, this study mainly answered three questions: Is there a significant relationship between teacher leadership and teacher well-being? Is there a significant mediating effect of trust in leaders on the relationship between teacher leadership and teacher well-being? Is there a significant mediating effect of teacher efficacy on the relationship between teacher leadership and teacher well-being?

Findings

This study reported a positive relationship between teacher leadership and teacher well-being. This study also found positive mediating roles for trust in leaders and teacher efficacy in the relationship between teacher leadership and teacher well-being in a high-accountability and hierarchical system like that of China.

Originality/value

This study provides an understanding of the transferability of teacher leadership theories across cultures and has practical significance for educational practice in high-accountability and hierarchical education contexts similar to that of China.
Predicting daily precision improvement of Jakarta Islamic Index in Indonesia’s Islamic stock market using big data mining
Authors: Ledhem Mohammed Ayoub , Moussaoui Warda
Published: September 2023

Purpose

This paper aims to apply several data mining techniques for predicting the daily precision improvement of Jakarta Islamic Index (JKII) prices based on big data of symmetric volatility in Indonesia’s Islamic stock market.

Design/methodology/approach

This research uses big data mining techniques to predict daily precision improvement of JKII prices by applying the AdaBoost, K-nearest neighbor, random forest and artificial neural networks. This research uses big data with symmetric volatility as inputs in the predicting model, whereas the closing prices of JKII were used as the target outputs of daily precision improvement. For choosing the optimal prediction performance according to the criteria of the lowest prediction errors, this research uses four metrics of mean absolute error, mean squared error, root mean squared error and R-squared.

Findings

The experimental results determine that the optimal technique for predicting the daily precision improvement of the JKII prices in Indonesia’s Islamic stock market is the AdaBoost technique, which generates the optimal predicting performance with the lowest prediction errors, and provides the optimum knowledge from the big data of symmetric volatility in Indonesia’s Islamic stock market. In addition, the random forest technique is also considered another robust technique in predicting the daily precision improvement of the JKII prices as it delivers closer values to the optimal performance of the AdaBoost technique.

Practical implications

This research is filling the literature gap of the absence of using big data mining techniques in the prediction process of Islamic stock markets by delivering new operational techniques for predicting the daily stock precision improvement. Also, it helps investors to manage the optimal portfolios and to decrease the risk of trading in global Islamic stock markets based on using big data mining of symmetric volatility.

Originality/value

This research is a pioneer in using big data mining of symmetric volatility in the prediction of an Islamic stock market index.