bluuebunny/crossref_metadata_2025 huggingface dataset:
BordetellaFilamentous hemagglutinin (FhaB) and Adenylyl cyclase toxin (ACT) interactions on the bacterial surface are consistent with FhaB-mediated delivery of ACT to phagocytic cells
Authors: Nash Zachary M. , Inatsuka Carol S. , Cotter Peggy A. , Johnson Richard M.
Published: September 2023

Bordetellaspecies that cause respiratory infections in mammals includeB. pertussis, which causes human whooping cough, andB. bronchiseptica, which infects nearly all mammals. Both bacterial species produce filamentous hemagglutinin (FhaB) and adenylyl cyclase toxin (ACT), prominent surface-associated and secreted virulence factors that contribute to persistence in the lower respiratory tract by inhibiting clearance by phagocytic cells. FhaB and ACT proteins interact with themselves, each other, and host cells. Using immunoblot analyses, we showed that ACT binds to FhaB preferentially on the bacterial surface before being released into the extracellular environment. We showed that SphB1, a surface protease identified based on its ability to cleave FhaB, also cleaves ACT, and we showed that the presence of ACT blocks SphB1-dependent and independent cleavage of FhaB, but the presence of FhaB does not block SphB1-dependent cleavage of ACT. SphB1-dependent cleavage of ACT occurs proximally to ACT’s active site, and hence is predicted to inactivate ACT. We also showed that FhaB-bound ACT can intoxicate host cells producing CR3, the receptor for ACT. In addition to increasing our understanding of FhaB, ACT, and ACT interactions on theBordetellasurface, our data support a model in which FhaB functions as a novel toxin delivery system by binding to ACT and allowing its release upon binding of ACT to its receptor, CR3, on phagocytic cells.

AUTHOR SUMMARY

Bacteria need to control the variety, abundance, and conformation of proteins on the cellular surface to survive. Members of the Gram-negative bacterial genusBordetellaincludeB. pertussis, which causes whooping cough in humans, andB. bronchiseptica, which causes respiratory infections in a broad range of mammals. These extremely closely related species produce two prominent virulence factors, the two-partner secretion (TPS) effector FhaB and Adenylyl cyclase toxin (ACT), that interact with themselves, each other, and host cells. In this work, we showed that ACT binds preferentially to FhaB on the bacterial surface before being released into the extracellular environment. We showed that the exoprotease SphB1, which cleaves FhaB, also cleaves ACT. We showed that ACT that is bound to FhaB can be delivered to CR3+host cells. Our data support a model in which FhaB functions to deliver ACT specifically to phagocytic cells, and not epithelial cells. This is the first report of a TPS system facilitating delivery of a separate polypeptide toxin to target cells and expands our understanding of how these systems contribute to bacterial pathogenesis.
Effects of mild winter conditions and two pyrethroid insecticides on the development and survival of juvenile common toads (Bufo bufo)
Authors: Kásler Andrea , Bókony Veronika , Mikó Zsanett , Herczeg Dávid , Ujszegi János , Holly Dóra , Hettyey Attila
Published: September 2023

Combined effects of pollutants and climate change can have long-term negative effects on Earth’s biodiversity. We tested how amphibians are affected by exposure to pesticides around metamorphosis in combination with current winter conditions or those projected to become the norm by 2100. We applied two pyrethroid insecticides, cypermethrin or deltamethrin, to newly metamorphosed common toads (Bufo bufo) via spraying, thereafter reared animals in outdoor enclosures, and finally exposed them either to a long&cold winter (1.5 °C for 91 days) or to a short&mild one (4.5 °C for 61 days). After hibernation, we examined changes in body mass, size and gross morphology of parotoid glands and visceral organs, and determined the phenotypic sex of the surviving toadlets. In the long&cold winter scenario, we observed high mortality rate, regardless of the chemical treatment (control: 82%, cypermethrin: 78%, deltamethrin: 70%). At the same time, mortality was significantly lower in the short&mild winter scenario (control: 33%, cypermethrin: 41%, deltamethrin: 26%). The decrease in body mass during overwintering did not differ among treatment groups. Our results contradict the hypothesis of sex-biased mortality caused by chemical pollutants, harsh or mild winter conditions or by their combination. No significant deformations of the internal organs were found in either group. Our results suggest that winter conditions becoming ever milder in the temperate zone may prove beneficial for amphibian overwinter survival, and that exposure to the tested pyrethroids at ecologically relevant concentrations after metamorphosis does not interfere with the fitness of juvenile common toads.
The catalytic mechanism of the RNA methyltransferase METTL3
Authors: Corbeski Ivan , Vargas-Rosales Pablo Andrés , Bedi Rajiv Kumar , Deng Jiahua , Coelho Dylan , Braud Emmanuelle , Iannazzo Laura , Li Yaozong , Huang Danzhi , Ethève-Quelquejeu Mélanie , Cui Qiang , Caflisch Amedeo
Published: September 2023

The complex of methyltransferase-like proteins 3 and 14 (METTL3-14) is the major enzyme that deposits N6-methyladenosine (m6A) modifications on mRNA in humans. METTL3-14 plays key roles in various biological processes through its methyltransferase (MTase) activity. However, little is known about its substrate recognition and methyl transfer mechanism from its cofactor and methyl donor S-adenosylmethionine (SAM). Here, we study the MTase mechanism of METTL3-14 by a combined experimental and multiscale simulation approach using bisubstrate analogues (BAs), conjugates of a SAM-like moiety connected to the N6-atom of adenosine. Molecular dynamics simulations based on crystal structures of METTL3-14 with BAs suggest that the Y406 side chain of METTL3 is involved in the recruitment of adenosine and release of m6A. A crystal structure with a bisubstrate analogue representing the transition state of methyl transfer shows a direct involvement of the METTL3 side chains E481 and K513 in adenosine binding which is supported by mutational analysis. Quantum mechanics/molecular mechanics (QM/MM) free energy calculations indicate that methyl transfer occurs without prior deprotonation of adenosine-N6. Furthermore, the QM/MM calculations provide further support for the role of electrostatic contributions of E481 and K513 to catalysis. The multidisciplinary approach used here sheds light on the (co)substrate binding mechanism, catalytic step, and (co)product release catalysed by METTL3, and suggests that the latter step is rate-limiting. The atomistic information on the substrate binding and methyl transfer reaction of METTL3 can be useful for understanding the mechanisms of other RNA MTases and for the design of transition state analogues as their inhibitors.

One sentence summary

A combined structural, biochemical, and computational approach reveals two distinct binding conformations of adenosine, the transition state of methyl transfer, and the catalytic mechanism of the human m6A RNA methyltransferase METTL3-14.
Optimisation of cell fate determination for cultured muscle differentiation
Authors: Melzener Lea , Schaeken Lieke , Fros Marion , Messmer Tobias , Raina Dhruv , Kiessling Annemarie , van Haaften Tessa , Spaans Sergio , Doǧan Arin , Post Mark J. , Flack Joshua E.
Published: September 2023

Production of cultured meat requires defined medium formulations for the robust differentiation of myogenic cells into mature skeletal muscle fibers in vitro. Whilst such formulations can drive myogenic differentiation to an extent similar to serum-starvation based protocols, these cultures are invariably heterogeneous in nature, with a significant proportion of cells not participating in myofusion, limiting maturation of the muscle. Here, we use RNA sequencing to characterise this heterogeneity at single-nucleus resolution, identifying distinct cellular subpopulations, including proliferative cells that fail to exit the cell cycle, and ’reserve cells’ that do not commit to myogenic differentiation. We show that the ERK, NOTCH and RXR pathways act during the first stages of myogenic cell fate determination, and by targeting these pathways, cell cycle exit can be promoted whilst abrogating reserve cell formation. Under these improved culture conditions, fusion indices close to 100% can be robustly obtained in 2D culture. Finally, we demonstrate that this translates to higher levels of myotube formation and muscle protein accumulation in animal component-free bioartificial muscle constructs, providing proof of principle for the generation of highly differentiated cultured muscle with excellent mimicry to traditional muscle.
SARS-CoV-2 ORF7a mutation found in BF.5 and BF.7 sublineages impacts its functions
Authors: Timilsina Uddhav , Duffy Sean R. , Plianchaisuk Arnon ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Ito Jumpei , Sato Kei , Stavrou Spyridon
Published: September 2023

A feature of the SARS-CoV-2 Omicron subvariants BF.5 and BF.7 that recently circulated mainly in China and Japan was the high prevalence of ORF7a: H47Y mutation. Here we evaluated the effect of this mutation on the three main functions ascribed to SARS-CoV-2 ORF7a protein. Our findings show that H47Y mutation impairs the ability of SARS-CoV-2 ORF7a to antagonize type-I interferon (IFN-I) response and to downregulate Major Histocompatibility Complex-I (MHC-I) cell surface levels, but had no effect in its anti-SERINC5 function. Overall, our results suggest that the H47Y mutation of ORF7a affects important functions of this protein resulting in changes in virus pathogenesis.

Importance

In late 2021, the Omicron (B.1.1.529) VOC emerged and outcompeted the circulating VOC Delta (B.1.617.2). Soon afterwards, Omicron VOC has expanded and diversified in the world. Among the emerged subvariants of Omicron are BF.5 and BF.7 that are characterized by the presence of a number of mutations across their genome and spread quite effectively across China and other countries later on. One such mutation that was found in the vast majority of isolates of the BF.5 and BF.7 subvariants was ORF7a: H47Y, whose effect on ORF7a is unknown. In this report, we show that H47Y inhibits a number of ORF7a functions, which can potentially affect virus pathogenesis.
Emerging many-to-one weighted mapping in hippocampus-amygdala network underlies memory formation
Authors: Liu Jun , Hall Arron F , Wang Dong V
Published: September 2023

Memories are crucial for our daily lives, yet the network-level organizing principle that governs neural representations of our experiences remains to be determined. Employing dual-site electrophysiology recording in freely behaving mice, we discovered that hippocampal dorsal CA1 (dCA1) and basolateral amygdala (BLA) utilize distinct coding strategies to represent novel experiences. A small assembly of BLA neurons rapidly emerged during memory acquisition and remained active during subsequent consolidation, whereas the majority of dCA1 neurons engaged in the same processes. Machine learning decoding revealed that dCA1 population spikes predicted the BLA assembly firing rate. This suggests that most dCA1 neurons concurrently index an episodic event by rapidly establishing weighted communications with a specific BLA assembly, a process we call “many-to-one weighted mapping.” Furthermore, we demonstrated that closed-loop optoinhibition of BLA activity triggered by dCA1 ripples after new learning resulted in impaired memory. These findings highlight a new principle of hippocampus-amygdala communication underlying memory formation and provide new insights into how the brain creates and stores memories.
Immunogenicity and tolerability of a SARS-CoV-2 TNX-1800, a live recombinant poxvirus vaccine candidate, in Syrian Hamsters and New Zealand White Rabbits
Authors: Awasthi Mayanka , Macaluso Anthony , Goebel Scott J , Luea Erin , Noyce Ryan S , Nasar Farooq , Daugherty Bruce , Bavari Sina , Lederman Seth
Published: September 2023

TNX-1800 is a preclinical stage synthetic derived live chimeric horsepox virus vaccine that comprises an engineered SARS-CoV-2 spike (S) gene expression cassette. The objectives of this study were to assess the immunogenicity and tolerability of TNX-1800 administration in Syrian golden hamsters and New Zealand white rabbits. Animals were vaccinated via percutaneous inoculation and evaluated for dose tolerance and immunogenicity at three different dose levels. The 28-day study data showed that the single percutaneous administration of three TNX-1800 vaccine dose levels was well tolerated in both hamsters and rabbits. For all dose levels, rabbits had more dermal observations than hamsters at the same dose levels. Vaccine-induced viral load four weeks post-dosing was below the detection level for both species.
Mycobacterium tuberculosisrequires conditionally essential metabolic pathways for infection
Authors: Block Alisha M. , Wiegert Parker C. , Namugenyi Sarah B. , Tischler Anna D.
Published: September 2023

New drugs are needed to shorten and simplify treatment of tuberculosis caused byMycobacterium tuberculosis. Metabolic pathways thatM. tuberculosisrequires for growth or survival during infection represent potential targets for anti-tubercular drug development. Genes and metabolic pathways essential forM. tuberculosisgrowth in standard laboratory culture conditions have been defined by genome-wide genetic screens. However, whetherM. tuberculosisrequires these essential genes during infection has not been comprehensively explored because mutant strains cannot be generated using standard methods. Here we show thatM. tuberculosisrequires functional phenylalanine (Phe) andde novopurine and thiamine biosynthetic pathways for mammalian infection. We used a defined collection ofM. tuberculosistransposon (Tn) mutants in essential genes, which we generated using a custom nutrient-rich medium, and transposon sequencing (Tn-seq) to identify multiple central metabolic pathways required for fitness in a mouse infection model. We confirmed by individual retesting and complementation that mutations inpheA(Phe biosynthesis) orpurF(purine and thiamine biosynthesis) cause death ofM. tuberculosisin the absence of nutrient supplementationin vitroand strong attenuation in infected mice. Our findings show that Tn-seq with defined Tn mutant pools can be used to identifyM. tuberculosisgenes required during mouse lung infection. Our results also demonstrate thatM. tuberculosisrequires Phe and purine/thiamine biosynthesis for survival in the host, implicating these metabolic pathways as prime targets for the development of new antibiotics to combat tuberculosis.

AUTHOR SUMMARY

Mycobacterium tuberculosiscauses more than 10 million new cases of active tuberculosis (TB) disease and 1.6 million deaths worldwide each year. Individuals with active TB must take a combination of four antibiotics for a minimum of 6-9 months to cure the infection. New anti-tubercular drugs are needed to simplify TB treatment and combat drug resistance. Here, we describe a novel collection ofM. tuberculosismutants lacking metabolic pathways essential for growth in standard laboratory conditions. Using these mutants, a mouse infection model, and deep sequencing we identified those metabolic pathways thatM. tuberculosisalso requires during infection. We find thatM. tuberculosismutants that cannot synthesize purine nucleotides, riboflavin, or certain amino acids are unable to grow in mice. We also find that mutant strains which cannot synthesize purine nucleotides or the amino acid phenylalanine die rapidly in laboratory cultures without nutrient supplementation, suggesting that new drugs targeting these pathways would killM. tuberculosis. Overall, our work reveals multiple metabolic pathways thatM. tuberculosisrequires during infection, which could be pursued as new targets for development of anti-tubercular drugs.
Interim influenza vaccine effectiveness estimates during the 2023 Southern Hemisphere season
Authors: Acevedo-Rodriguez J Gonzalo , Zamudio Carlos , Kojima Noah , Krapp Fiorella , Tsukayama Pablo , Neciosup-Vera C Stefany , Gotuzzo Eduardo
Published: September 2023

Our findings suggest that a substantial number of people sought care for CLI during an early Southern Hemisphere season during which A/H1N1pdm09 clade 6B.1A.5a.2a viruses predominated. The minority vaccinated benefitted from the A/Victoria/2570/2019 (H1N1)pdm09-like antigen which afforded good protection against illness.
Beneficial changes in the gut microbiome of patients with multiple sclerosis after consumption of Neu-REFIX B-glucan in a clinical trial
Authors: Dedeepiya Vidyasagar Devaprasad , Vetrievel Chockanathan , Ikewaki Nobunao , Yamamoto Naoki , Kawashima Hiroto , Ichiyama Koji , Senthilkumar Rajappa , Preethy Senthilkumar , Abraham Samuel JK
Published: September 2023

Background

Multiple sclerosis (MS) is a debilitating demyelinating disease and recent evidences are giving cues towards correlation of disease severity to gut microbiome dysbiosis. However, there haven’t been any reported interventions that beneficially modifies the gut microbiome to yield a clinically discernible improvement. Having earlier reported the clinical effects of a biological response modifier beta-glucan (BRMG) produced by the N-163 strain ofAureobasidum pullulans, commercially available as Neu-REFIX, which decreased the biomarkers of inflammation and produced beneficial immune-modulation in twelve MS patients in 60 days, we evaluated their gut microbiome in the present study.

Methods

Twelve patients diagnosed with MS participated in the study. Each consumed 16 g gel of the NEU-REFIX beta-Glucan for 60 days. Whole genome metagenomic sequencing was performed on the fecal samples before and after Neu-REFIX intervention.

Results

Post-intervention analysis showed thatActinobacteriafollowed byBacteroideswas the major family. Abundance of beneficial genera such asBifidobacterium, Collinsela, Prevotella, Lactobacillusand species such asPrevotella copri (p-value=0.4), Bifidobacterium longum (p-value=0.2), Faecalibacterium prausnitzii (p-value=0.06), Siphoviridae (p-value=0.06)increased while inflammation associated genera such asBlautia (p-value=0.06),Ruminococcus (p-value=0.007)andDorea (p-value = 0.03)decreased in abundance.

Conclusion

Restoration of gut eubiosis in terms of both increase in abundance of the good microbiome and suppression of the harmful ones which also correlate with earlier reported clinical improvement in MS patients makes this Neu-REFIX beta-glucan, a potential disease modifying therapy (DMT) requiring larger studies for validation in MS and other auto-immune-inflammatory conditions where a safe intervention for immune modulation is vital.
Convergent alterations in the tumor microenvironment of MYC-driven human and murine prostate cancer
Authors: Graham Mindy K , Wang Rulin , Chikarmane Roshan , Wodu Bulouere , Vaghasia Ajay , Gupta Anuj , Zheng Qizhi , Hicks Jessica , Sysa-Shah Polina , Pan Xin , Castagna Nicole , Liu Jianyong , Meyers Jennifer , Skaist Alyza , Zhang Yan , Schuebel Kornel , Simons Brian W , Bieberich Charles J. , Nelson William G , Lupold Shawn E. , DeWeese Theodore L , De Marzo Angelo M , Yegnasubramanian Srinivasan
Published: September 2023

The tissue microenvironment in prostate cancer is profoundly altered. While such alterations have been implicated in driving prostate cancer initiation and progression to aggressive disease, how prostate cancer cells and their precursors mediate those changes is unclear, in part due to the inability to longitudinally study the disease evolution in human tissues. To overcome this limitation, we performed extensive single-cell RNA-sequencing (scRNA-seq) and rigorous molecular pathology of the comparative biology between human prostate cancer and key time points in the disease evolution of a genetically engineered mouse model (GEMM) of prostate cancer. Our studies of human tissues, with validation in a large external data set, revealed that cancer cell-intrinsic activation of MYC signaling was the top up-regulated pathway in human cancers, representing a common denominator across the well-known molecular and pathological heterogeneity of human prostate cancer. Likewise, numerous non-malignant cell states in the tumor microenvironment (TME), including non-cancerous epithelial, immune, and fibroblast cell compartments, were conserved across individuals, raising the possibility that these cell types may be a sequelae of the convergent MYC activation in the cancer cells. To test this hypothesis, we employed a GEMM of prostate epithelial cell-specific MYC activation in two mouse strains. Cell communication network and pathway analyses suggested that MYC oncogene-expressing neoplastic cells, directly and indirectly, reprogrammed the TME during carcinogenesis, leading to the emergence of cascading cell state alterations in neighboring epithelial, immune, and fibroblast cell types that paralleled key findings in human prostate cancer. Importantly, among these changes, the progression from a precursor-enriched to invasive-cancer-enriched state was accompanied by a cell-intrinsic switch from pro-immunogenic to immunosuppressive transcriptional programs with coinciding enrichment of immunosuppressive myeloid and Treg cells in the immune microenvironment. These findings implicate activation of MYC signaling in reshaping convergent aspects of the TME of prostate cancer as a common denominator across the otherwise well-documented molecular heterogeneity of human prostate cancer.
Speciation in kleptoparasites of oak gall wasps often correlates with a shift into a new tree habitat, tree organ, or gall morphospace
Authors: Ward Anna K.G. , Zhang Y. Miles , Brown Guerin E. , Hippee Alaine C. , Prior Kirsten M. , Rollins Shannon , Sierra Nicolas , Sheikh Sofia I. , Tribull Carly M. , Forbes Andrew A.
Published: September 2023

Host shifts to new plants can drive speciation for plant-feeding insects, but how commonly do host shifts also drive diversification for the parasites of those same insects? Oak gall wasps induce galls on oak trees and shifts to novel tree hosts and new tree organs have been implicated as drivers of oak gall wasp speciation. Gall wasps are themselves attacked by many insect parasites, which must find their hosts on the correct tree species and organ, but which also must navigate the morphologically variable galls with which they interact. Thus, we ask whether host shifts to new trees, organs, or gall morphologies correlate with gall parasite diversification. We delimit species and infer phylogenies for two genera of gall kleptoparasites,SynergusandCeroptres, reared from a variety of North American oak galls. We find that most species were reared from galls induced by just one gall wasp species, and no parasite species was reared from galls of more than four species. Most kleptoparasite divergence events correlate with shifts to non-ancestral galls. These shifts often involved changes in tree habitat, gall location, and gall morphology. Host shifts are thus implicated in driving diversification for both oak gall wasps and their kleptoparasitic associates.
Unveiling the Intercompartmental Signaling Axis: Mitochondrial to ER Stress Response (MERSR) and its Impact on Proteostasis
Authors: Li Jeson J , Xin Nan , Yang Chunxia , Tavizon Larissa A , Hong Ruth , Park Jina , Moore Travis I , Tharyan Rebecca George , Antebi Adam , Kim Hyun-Eui
Published: September 2023

Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPRERis inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2α signaling pathway, increasing phosphorylation of eIF2α and improving the ER’s ability to handle proteostasis. MERSR activation in both polyglutamine and amyloid-beta peptide-expressingC. elegansdisease models also led to improvement in both aggregate burden and overall disease outcome. These findings shed light on the coordination between the mitochondria and the ER in maintaining cellular proteostasis and provide further evidence for the importance of intercompartmental signaling.
Organ-specific prioritization and annotation of non-coding regulatory variants in the human genome
Authors: Zhao Nanxiang , Dong Shengcheng , Boyle Alan P
Published: September 2023

Identifying non-coding regulatory variants in the human genome remains a challenging task in genomics. Recently we advanced our leading regulatory variant database, RegulomeDB, to its second version. Building upon this comprehensive database, we developed a novel machine-learning architecture with stacked generalization, TLand, which utilizes RegulomeDB-derived features to predict regulatory variants at cell or organ-specific levels. In our holdout benchmarking, TLand consistently outperformed state-of-the-art models, demonstrating its ability to generalize to new cell lines or organs. We trained three types of organ-specific TLand models to overcome the common model bias toward high data availability cell lines or organs. These models accurately prioritize relevant organs for 2 million GWAS SNPs associated with GWAS traits. Moreover, our analysis of top-scoring variants in specific organ models showed a high enrichment of relevant GWAS traits. We expect that TLand and RegulomeDB will further advance our ability to understand human regulatory variants genome-wide.
Disease prevalence, health-related and socio-demographic factors in the GCAT cohort. A comparison with the general population of Catalonia
Authors: Blay Natalia , Carrasco-Ribelles Lucía A , Farré Xavier , Iraola-Guzmán Susana , Danés-Castells Marc , Violán Concepción , de Cid Rafael
Published: September 2023

Background

Population-based cohorts play a key role in epidemiological studies. However, it is known that volunteer cohorts include a healthy volunteer bias. Assessment and characterization of this bias is needed to extrapolate results to the general population. Here, we assess the bias of the population-based cohort GCAT, encompassing 20 000 adult participants from Catalonia with electronic health record data. The aim of this study is to compare the GCAT cohort with its age-matching Catalan population, to assess their representativeness, as well as determining the weights to make results generalisable.

Methods

Statistical comparisons until 2019 in multiple variables across sociodemographic, lifestyle, diseases and medication domains were performed by stratified analysis with Fisher’s exact test and t-test. Electronic health records of Catalonia (SIDIAP), and registers from the statistics institute of Catalonia (IDESCAT) and Spain (INE) were used to make the comparisons. We generated weights accounting for sociodemographic, lifestyle and multimorbidity factors.

Results

GCAT cohort is enriched in women and younger individuals, with higher socioeconomic status, more health conscious and healthier in terms of mortality and chronic disease prevalence. We have shown that this bias can be corrected with weighting techniques, providing a more representative sample of the general population.

Conclusions

The application of multidomain weights, encompassing not only sociodemographic aspects, but also lifestyle and health-related variables, has effectively diminished the observed bias in disease prevalence estimates within the GCAT cohort. This correction has led to an enhancement of the cohort’s representativeness, rendering it more akin to the general population of Catalonia.
Chronic deregulation of the spindle assembly checkpoint triggers myelosuppression and gastrointestinal atrophy
Authors: Karbon Gerlinde , Schuler Fabian , Haschka Manuel , Drach Mathias , Sotillo Rocio , Geley Stephan , Spierings Diana C.M. , Tijhuis Andrea E. , Foijer Floris , Villunger Andreas
Published: September 2023

Interference with microtubule dynamics in mitosis activates the spindle assembly checkpoint (SAC) to prevent chromosome segregation errors. The SAC induces mitotic arrest by inhibiting the anaphase-promoting complex (APC) via the mitotic checkpoint complex (MCC). The MCC component MAD2 neutralises the critical APC cofactor, CDC20, preventing mitotic exit. In cancer cell lines, this can provoke apoptosis involving pro-apoptotic BCL2 family members BIM and NOXA while BCL2 overexpression blocks mitotic cell death, facilitating SAC adaptation. However, the consequences of apoptosis after SAC perturbation in vivo are unclear. By conditional MAD2 overexpression across tissues in mice, we observed that chronic SAC activation triggers bone marrow aplasia and intestinal atrophy. While myelosuppression was tolerated, gastrointestinal atrophy was detrimental. Remarkably, co-deletion of Bim/Bcl2l11, but not Bid, Puma/Bbc3 or Noxa/Pmaip, prevented developing gastrointestinal syndrome caused by chronic SAC activity, identifying BIM as rate-limiting for mitotic cell death in the gastrointestinal epithelium. In contrast, only BCL2 overexpression but none of the BH3-only protein deficiencies tested could mitigate myelosuppression, highlighting tissue and cell type-specific survival dependencies in response to SAC perturbation in vivo.
Information on the processing of organic food: consumers' perception
Authors: Sinesio Fiorella , Saba Anna , Moneta Elisabetta , Peparaio Marina , Saggia Civitelli Eleonora , Paoletti Flavio
Published: September 2023

Purpose

The study aimed to investigate consumers’ views on criteria to be claimed for organic processed foods and information to be communicated.

Design/methodology/approach

An online survey was carried out among 439 adults living in Italy, users of processed organic food, to gather opinions on criteria that processing of organic food should meet and on the terms that best define “careful” processing. Next, a conjoint design was applied to examine the effects of five independent factors on consumers' ideal concept of “organic”; these were potential information on packaging, processing, additives and product quality, and the type of food product. Three products with different processing level were selected: an ultra-processed and multi-ingredient product (vegetable burger), a processed product preserved by canning (peas in glass jar) and a minimally processed product (bagged salad).

Findings

The findings highlight that consumers attach more importance to the organic food carrier than the informational messages. Information on the processing and packaging follows, with messages on quality and on additives seemingly of minor importance. Three clusters of respondents were identified: those driven primarily by the type of organic food (24.6%), those placing more emphasis on product processing (21.3%), and a third larger cluster (54.1%) who expressed almost equal importance to all the factors considered. As for the processing of organic products, “eco-friendly” was the best message.

Originality/value

This paper offers insights into what best outlines the ideal concept of “processed organic food” as seen by organic food consumers, to be communicated to better guide their purchasing decisions.
Multidimensional knowledge discovery of cultural relics resources in the Tang tomb mural category
Authors: Gao Ying , Zhang Qiang , Wang Xiaoran , Huang Yanmei , Meng Fanshuang , Tao Wan
Published: September 2023

Purpose

Currently, the Tang tomb mural cultural relic resources are presented in a multi-source and heterogeneous manner, with a lack of effective organization and sharing between resources. Therefore, this study aims to propose a multidimensional knowledge discovery solution for Tang tomb mural cultural relic resources.

Design/methodology/approach

Taking the Tang tomb murals collected by the Shaanxi History Museum as an example, based on clarifying the relevant concepts of Tang tomb mural resources and considering both dynamic and static dimensions, a top-down approach was adopted to first construct an ontology model of Tang tomb mural type cultural relics resources. Then, the actual case data was imported into the Neo4J graph database according to the defined pattern hierarchy to complete the static organization of knowledge, and presented in a multimodal form in knowledge reasoning and retrieval. In addition, geographic information system (GIS) technology is used to dynamically display the spatiotemporal distribution of Tang tomb mural resources, and the distribution trend is analysed from a digital humanistic perspective.

Findings

The multi-dimensional knowledge discovery of Tang tomb mural cultural relics resources can help establish the correlation and spatiotemporal relationship between resources, providing support for semantic retrieval and navigation, knowledge discovery and visualization and so on.

Originality/value

This study takes the murals in the collection of the Shaanxi History Museum as an example, revealing potential knowledge associations in a static and intelligent way, achieving knowledge discovery and management of Tang tomb murals, and dynamically presents the spatial distribution of Tang tomb murals through GIS technology, meeting the knowledge presentation needs of different users and opening up new ideas for the study of Tang tomb murals.
Money laundering: effectiveness of the corporate social responsibility (CSR) law in the UAE
Authors: Al-Tawil Tareq Na′el
Published: September 2023

Purpose

The purpose of this paper is to examine the extent to which the corporate social responsibility (CSR) law will help combat money laundering in the United Arab Emirates (UAE).

Design/methodology/approach

The paper will first focus on examining whether money laundering and CSR are compatible. Such an analysis will then inform decisions on whether to include anti-money laundering in CSR disclosure requirements.

Findings

Key findings from the analysis have shown that the UAE CSR law does not explicitly mention money laundering as part of CSR disclosure requirements. Anti-money laundering (AML) and CSR are compatible and convergence, but money laundering is not yet an integral element of CSR disclosure requirements.

Originality/value

There are no clear mechanisms or provisions under the UAE CSR law on how money laundering can be included in CSR disclosure requirements, whether voluntary or mandatory. A pressing challenge now is whether the UAE should regulate AML/combatting the financing of terrorism disclosures under the CSR law. The main concern is that such a move could make mandatory disclosure another technical and regulatory requirement that UAE business must comply, which will be inimical to fostering a strong CSR culture.
Expanding financial inclusion in Indonesia through Takaful: opportunities, challenges and sustainability
Authors: Alhammadi Salah
Published: September 2023

Purpose

This study aims to investigate the relationship between financial inclusion and sustainable economic development in Indonesia by exploring the potential impact of Takaful. Specifically, the study seeks to examine the feasibility of leveraging Takaful as a means to foster financial inclusion and drive economic growth in Indonesia.

Design/methodology/approach

This study uses a qualitative analysis methodology, specifically using content analysis techniques, to investigate the relationship between financial inclusion and sustainable economic growth in Indonesia, focussing on the role of Takaful. The content analysis enables a systematic study of the data to identify trends and topics pertinent to Takaful and its potential to advance financial inclusion.

Findings

The study’s results reveal a direct causal link between economic growth and achieving financial inclusion through the use of Takaful. The findings also indicate a positive correlation between the increased presence of Takaful markets and accelerated economic growth.

Research limitations/implications

The study examines only the use of Takaful in achieving financial inclusion and sustainable economic growth in Indonesia. Nonetheless, the practical implications of this research are substantial, as they highlight the potential of Takaful to foster financial inclusion and stimulate economic growth in Indonesia.

Practical implications

This study contributes to the limited body of research on the relationship between financial inclusion and economic growth in Indonesia, specifically in the context of Takaful.

Originality/value

This study’s value lies in its exploration of an under-researched area, providing crucial insights into the potential of Takaful to promote financial inclusion and drive economic growth in Indonesia. The social implications of this study are also noteworthy, as increased financial inclusion and economic growth can positively affect poverty reduction, job creation and overall societal well-being in Indonesia.
Trends of research on women's entrepreneurship on the management of happiness and well-being in organisations
Authors: de las Heras-Pedrosa Carlos , Jambrino-Maldonado Carmen , Rando-Cueto Dolores , Iglesias-Sánchez Patricia P.
Published: September 2023

Purpose

The management of employee happiness and well-being has been gaining interest in academic research in recent years; however, few studies have focussed on the entrepreneur's perspective. The aim of this paper is to analyse the state of research on women-led businesses, well-being and happiness management.

Design/methodology/approach

A bibliometric study has been carried out since 1996, the first year in which publications in this field were detected. In total, 128 papers are identified in the most reliable database, Web of Science Core Collection. A network mapping of authorship, citation and co-occurrence of keywords in scientific publications is shown.

Findings

The results of this study confirm that societal changes resulting from crises increase research interest in improving organisational environments and happiness. After the economic crises of 2013, there was a boost, and after the pandemic, there is again a boost in research. More than half of the publications and citations on female entrepreneurship and happiness management are post-pandemic. The study offers some research directions and emphasises the role of gender.

Originality/value

This article brings a new approach to the study of well-being in organisations, highlighting the relevance of the role female leadership plays in promoting happiness at work.
Rethinking sustainability in cocoa supply chain in light of SDG disclosure
Authors: Martins Flávio P. , Batalhão André C.S. , Ahokas Minna , Liboni Amui Lara Bartocci , Cezarino Luciana O.
Published: September 2023

Purpose

This paper aims to assess how cocoa supply chain companies disclose sustainable development goals (SDGs) information in their sustainability reports. This assessment highlights strategic aspects of sustainable supply chain management and reveals leveraging sustainability points in the cocoa industry.

Design/methodology/approach

The two-step qualitative approach relies on text-mining company reports and subsequent content analysis that identifies the topics disclosed and relates them to SDG targets.

Findings

This study distinguishes 18 SDG targets connected to cocoa traders and 30 SDG targets to chocolate manufacturers. The following topics represent the main nexuses of connections: decent labour promotion and gender equity (social), empowering local communities and supply chain monitoring (economic) and agroforestry and climate action (environmental).

Practical implications

By highlighting the interconnections between the SDGs targeted by companies in the cocoa supply chain, this paper sheds light on the strategic SDGs for this industry and their relationships, which can help to improve sustainability disclosure and transparency. One interesting input for companies is the improvement of climate crisis prevention, focusing on non-renewable sources minimisation, carbon footprint and clear indicators of ecologic materiality.

Social implications

This study contributes to policymakers to enhance governance and accountability of global supply chains that are submitted to different regulation regimes.

Originality/value

To the best of the authors’ knowledge, no previous study has framed the cocoa industry from a broader SDG perspective. The interconnections identified reveal the key goals of the cocoa supply chain and point to strategic sustainability choices for companies in an important global industry.
Predicting cause-related marketing patronage intentions, corporate social responsibility motives and moderating role of spirituality
Authors: Suryavanshi A.K.S. , Bhatt Viral , Thomas Sujo , Patel Ritesh , Jariwala Harsha
Published: September 2023

Purpose

Recent studies have observed rise in consumer’s ethical concerns about the online retailers while making a purchase decision. The impetus for businesses to use corporate social responsibility (CSR) is evident, but the effects of CSR motives on corresponding processes underlying cause-related marketing (CRM) patronage intention have not been thoroughly examined. This study, anchored on attribution theory, established a research model that better explains the influence of CSR motives on patronage intentions toward CRM-oriented online retailers. Additionally, this study aims to examine the moderating role of spirituality (SPT) on CSR motives and CRM patronage intention (CPI).

Design/methodology/approach

Primary data has been collected from 722 respondents and analyzed by using deep neural-network architecture by using the innovative PLS-SEM-ANN method to predict/rank the factors impacting CPI.

Findings

The results revealed the normalized importance of the predictors of CPI and found that value-driven motive was the strongest predictor, followed by strategic motive, SPT, age and stakeholder-driven motive. In contrast, egoistic motive, education and income were found insignificant.

Originality/value

The pandemic has transformed the way consumers shop and fortified the online economy, thereby resulting in a paradigm shift toward usage of e-commerce platforms. The results offer valuable insights to online retailers and practitioners for predicting patronage intentions by CSR motives and, thus, effectively engage CRM consumers by designing promotions in a way that would deeply resonate with them. This study assessed and predicted the factors influencing the CPI s, thereby guiding the online retailers to design CSR strategies and manage crucial CRM decisions.
Drosophila X virus‐like particles as delivery carriers for improved oral insecticidal efficacy of scorpion Androctonus australis peptide against the invasive fruit fly, Drosophila suzukii
Authors: Xue Qi , Swevers Luc , Taning Clauvis Nji Tizi
Published: September 2023

Insect‐specific neurotoxic peptides derived from the venoms of scorpions and spiders can cause acute paralysis and death when injected into insects, offering a promising insecticidal component for insect pest control. However, effective delivery systems are required to help neurotoxic peptides pass through the gut barrier into the hemolymph, where they can act. Here, we investigated the potential of a novel nanocarrier, Drosophila X virus‐like particle (DXV‐VLP), for delivering a neurotoxin from the scorpion Androctonus australis Hector (AaIT) against the invasive pest fruit fly, Drosophila suzukii. Our results show that the fusion proteins of DXV polyproteins with AaIT peptide at their C‐termini could be sufficiently produced in Lepidoptera Hi5 cells in a soluble form using the recombinant baculovirus expression system, and could self‐assemble into VLPs with similar particle morphology and size to authentic DXV virions. In addition, the AaIT peptides displayed on DXV‐VLPs retained their toxicity, as demonstrated in injection bioassays that resulted in severe mortality (72%) in adults after 72 h. When fed to adults, mild mortality was observed in the group treated with DXV‐AaIT (38%), while no mortality occurred in the group treated with AaIT peptide, thus indicating the significant role of DXV‐VLPs in delivering AaIT peptides. Overall, this proof‐of‐concept study demonstrates for the first time that VLPs can be exploited to enhance oral delivery of insect‐specific neurotoxic peptides in the context of pest control. Moreover, it provides insights for further improvements and potentially the development of neurotoxin‐based bioinsecticides and/or transgenic crops for insect pest control.
Formulation of pasta enriched with protein‐rich lupine (Lupinus mutabilis Sweet) and wheat bran using mixture design approach
Authors: Karoui Iness Jabri , Terras Dorra Sfayhi , Yeddes Walid , Hammami Majdi , Abderrabba Manef
Published: September 2023

In recent years, as awareness of healthy diets has increased, consumers are becoming more aware of their food and are paying more attention to their diet. Nutritionists have recommended an increased consumption of dietary fiber in the daily diet to improve health. Within this context, this work aims to formulate “spaghetti” pasta enriched with lupin flour and wheat bran. For the formulation of the mixture of those flours, we used the NemrodW software to predict the optimal pasta formula. A physicochemical characterization, as well as the culinary quality of the pasta resulting from the different mixtures, was carried out to model each significant criterion and choose the optimal mixture that will be used in the pasta recipe. The evaluation of the physicochemical characteristics of the pasta showed that the addition of lupin flour and bran resulted in an improvement in the nutritional value of the enriched spaghetti. Following the results obtained, the software proposed an optimal mix and will be used for further study. This formula comprises 19.60% bran, 27.83% lupin flour, and 52.75% durum wheat semolina. The caloric value of the dough from the optimal mix was determined and compared to that of the standard dough. The results of our study indicated a significant improvement in the nutritional value of the enriched pasta compared to the standard pasta. The enriched pasta contained higher levels of protein, ash, lipids, polyphenols, and pigments and lower levels of sugars, which make it a more nutritious option for certain individuals, such as athletes or those following a protein or low‐sugar diet.

Practical Application

The proposed method of substituting wheat semolina with lupine flour and wheat bran in spaghetti formulation has demonstrated a potential for producing protein‐rich and nutritionally enriched pasta. This approach can be useful for developing similar functional food products that cater to the dietary requirements of athletes or individuals following a protein or low‐sugar diet.