bluuebunny/crossref_metadata_2025 huggingface dataset:
RND pumps across the genus Acinetobacter: AdeIJK is the universal efflux pump
Authors: Darby Elizabeth M. , Bavro Vassiliy N. , Dunn Steven , McNally Alan , Blair Jessica M. A.
Published: March 2023

Acinetobacter

are generally soil-dwelling organisms that can also cause serious human infections.

A. baumannii

is one of the most common causative agents of

Acinetobacter

infections and is often multidrug resistant. However, an additional 25 species within the genus have also been associated with infection.

A. baumannii

encodes six resistance nodulation division (RND) efflux pumps, the most clinically relevant class of efflux pumps for antibiotic export, but the distribution and types of RND efflux pumps across the genus is currently unknown. Sixty-four species making up the genus

Acinetobacter

were searched for RND systems within their genomes. We also developed a novel method using conserved RND residues to predict the total number of RND proteins including currently undescribed RND pump proteins. The total number of RND proteins differed both within a species and across the genus. Species associated with infection tended to encode more pumps. AdeIJK/AdeXYZ was found in all searched species of Acinetobacter, and through genomic, structural and phenotypic work we show that these genes are actually homologues of the same system. This interpretation is further supported by structural analysis of the potential drug-binding determinants of the associated RND-transporters, which reveal their close similarity to each other, and distinctiveness from other RND-pumps in

Acinetobacter

, such as AdeB. Therefore, we conclude that AdeIJK is the fundamental RND system for species in the genus

Acinetobacter

. AdeIJK can export a broad range of antibiotics and provides crucial functions within the cell, for example lipid modulation of the cell membrane, and therefore it is likely that all

Acinetobacter

require AdeIJK for survival and homeostasis. In contrast, additional RND systems, such as AdeABC and AdeFGH, were only found in a subset of

Acinetobacter

that are associated with infection. By understanding the roles and mechanisms of RND efflux systems in

Acinetobacter

, treatments for infections can avoid efflux-mediated resistance and improve patient outcomes.
Optical control of cardiac rhythm byin vivophotoactivation of an ERG channel peptide inhibitor
Authors: Montnach Jérôme , Millet Hugo , Persello Antoine , Meudal Hervé , Waard Stephan De , Mesrica Pietro , Ribeiro Barbara , Richard Jérémie , Hivonnait Agnès , Tessier Agnès , Lauzier Benjamin , Charpentier Flavien , Mangoni Matteo E. , Landon Céline , Jopling Chris , De Waard Michel
Published: March 2023

RATIONALE

Cardiac rhythm, conduction and synchronization of electrical activity require the coordinated action of different types of ion channels that differ according to transmural and regional specificities. Classical pharmacology affects these ion channels in a non-regionalized way which explains why treating arrhythmias, that often occur in specific foci, has often limited efficacy in addition to negative side-effects on non-targeted organs. Photopharmacology is an emergent technology that has the potential to counteract all the negative aspects of classical pharmacology by restricting drug activity in a spatio-temporal manner.

OBJECTIVE

We tested the potential of photopharmacology in specifically regulating heart activity by using a caged derivative of a natural peptide inhibitor of the ERG channel, BeKm1. The peptide was uncaged and activity monitoredin vitroon a cell line expressing the hERG channel, on human cardiomyocytes derived from iPS cells, andex vivoandin vivoon zebrafish larvae and rat hearts.

METHODS AND RESULTS

Caged BeKm-1 is inactive and fully active upon uncaging. Uncaging of the peptide on human iPS-derived cardiomyocytes enlarges the action potential duration and triggers arrhythmias. Uncaging also triggers bradycardia and disturbs cardiac conduction within the atria in perfused rat hearts upon illumination. The potency of photopharmacology for cardiac electrical modulation was further validated in zebrafish larvae where illumination of the caged compound induces bradycardia and atrio-ventricular desynchrony. Finally, in anesthetized rats, illumination of the caged peptide in the right atria, containing the sino-atrial node, leads to bradycardia without arrhythmia.

CONCLUSIONS

This report demonstrates that photopharmacology, using the caged peptide strategy, can be used for dynamically regulating cardiac electrical activityin vivoand that spatial illumination restriction can dissociate the bradycardic effect from the arrhythmic one. The technology is applicable to all kinds of cardiac ion channels and regions of interest to create arrhythmogenic models or investigate new clinical applications.
Diagnosing and remediating harmful data shifts for the responsible deployment of clinical AI models
Authors: Subasri Vallijah , Krishnan Amrit , Dhalla Azra , Pandya Deval , Malkin David , Razak Fahad , Verma Amol A. , Goldenberg Anna , Dolatabadi Elham
Published: March 2023

Harmful data shifts occur when the distribution of data used to train a clinical AI system differs significantly from the distribution of data encountered during deployment, leading to erroneous predictions and potential harm to patients. We evaluated the impact of data shifts on an early warning system for in-hospital mortality that uses electronic health record data from patients admitted to a general internal medicine service, across 7 large hospitals in Toronto, Canada. We found model performance to differ across subgroups of clinical diagnoses, sex and age. To explore the robustness of the model, we evaluated potentially harmful data shifts across demographics, hospital types, seasons, time of hospital admission, and whether the patient was admitted from an acute care institution or nursing home, without relying on model performance. Interestingly, many of these harmful data shifts were unidirectional. We found models trained on community hospitals experience harmful data shifts when evaluated on academic hospitals, whereas models trained on academic hospitals transfer well to the community hospitals. To improve model performance across hospital sites we employed transfer learning, a strategy that stores knowledge gained from learning one domain and applies it to a different but related domain. We found hospital type-specific models that leverage transfer learning, perform better than models that use all available hospitals. Furthermore, we monitored data shifts over time and identified model deterioration during the COVID-19 pandemic. Typically, machine learning models remain locked after deployment, however, this can lead to model deterioration due to harmful data shifts that occur over time. We used continual learning, the process of learning from a continual stream of data in a sequential manner, to mitigate data shifts over time and improve model performance. Overall, our study is a crucial step towards the deployment of clinical AI models, by providing strategies and workflows to ensure the safety and efficacy of these models in real-world settings.
The association of genetically proxied sildenafil with fertility, sexual activity, and wellbeing: a Mendelian randomisation study
Authors: Woolf Benjamin , Rajasundaram Skanda , Cronjé Héléne T. , Yarmolinsky James , Burgess Stephen , Gill Dipender
Published: March 2023

Objective

To investigate the association of genetically proxied Phosphodiesterase 5 (PDE5) inhibition with fertility, sexual activity, and subjective wellbeing in men.

Design

Two-samplecis-Mendelian randomisation.

Setting

Genetic association data obtained from the International Consortium for Blood Pressure (ICBP) and UK Biobank (UKB).

Participants

European ancestry individuals from the ICBP (N= 757,601) and the UKB (N≈ 450,000). Genetic association data were leveraged from the ICBP for the exposure and from the UKB for the outcomes.

Intervention

Genetically proxied PDE5 inhibition, scaled to the effect of 100mg daily sildenafil on diastolic blood pressure.

Main outcome measures

Number of children, age of first having sex, number of sexual partners, odds of being a virgin and self-reported wellbeing, all measured in the male sub-sample of the UKB.

Secondary outcomes

To explore the specificity of our results, we replicate our analysis in the female sub-sample of the UKB. We additionally explored possible confounders/mediators of our instruments using PhenoScanner, and adjust for them using Two-stepcis-MR.

Results

Genetically proxied sildenafil was associated with fathering 0.21 (95% CI: 0.08– 0.35) more children (FDR corrected p = 0.01). This association was neither attenuated when adjusting for traits associated with our instruments nor was it replicated in women. We did not find robust evidence for an effect of sildenafil on the age of first having sex, number of sexual partners, odds of being a virgin, or self-reported wellbeing.

Conclusions

This study provides genetic support for PDE5 inhibitors increasing the number of children that men have.

Key Messages

-

Sildenafil is a PDE5 inhibitor that is commonly used in the treatment of erectile dysfunction and pulmonary hypertension.

-

Drug-target Mendelian randomisation is a quasi-experimental method that uses genetic variants to proxy drug-target perturbation. Here, we leverage this approach to investigate long-term therapeutic and adverse effects of sildenafil use, many of which cannot be easily evaluated in a randomised controlled trial.

-

We find evidence for a casual association between genetically proxied sildenafil use and number of children fathered. Genetically proxied sildenafil use was not associated with age at first having sex, number of sexual partners, odds of being a virgin, or subjective wellbeing.
EVALUATION OF A METAGENOMIC NEXT-GENERATION SEQUENCING ASSAY WITH A NOVEL HOST DEPLETION METHOD FOR PATHOGEN IDENTIFICATION IN SEPTIC PATIENTS
Authors: Chen Yen-Chia , Liao Po-Hsiang , Chen Yen-Wen , Chang Chia-Ming , Chan Maurice , Chao Deng Fong , Lin Yizhen , Chang Jiahao , Hung Hau , Wu Mengchu , Yen David Hung-Tsang
Published: March 2023

Background

The traditional diagnosis of sepsis has always been based on microbial blood culture (BC). However, BC suffers from (1) long culture cycle, leading to delay in results, and (2) low diagnostic yields. Metagenomic next-generation sequencing (mNGS) has been proposed as an efficient and agnostic option that potentially overcomes these issues. In this study, a mNGS workflow utilizing a novel filter to specifically capture white blood cells and deplete host DNA background, was evaluated against BC results, as well as mNGS without host depletion, for pathogen identification.

Materials and Methods

Patients admitted to Taipei Veterans General Hospital (TVGH) with suspected sepsis were recruited to the study approved by the IRB. Blood sample was taken for BC (designated as BC1) before any antibiotic exposure. Upon patient enrolment, blood was taken again and divided in 3 portions with one used for the 2ndBC (BC2). The other two were used for mNGS with one processed with the filter and the other without filtering, to assess the effectiveness of host-depletion by the filter.

Results

A total of 50 patients were recruited among which 45 had results for all 4 tests. mNGS with filter had the highest positive rate of 74.4%, followed by mNGS without filter and BC1 (51.1% and 50.0% respectively), while the 2ndBC had the lowest positive rate of 22.0%. Further, mNGS was less sensitive to antibiotics exposure as compared to BC. The overall correlation between samples with vs without filtration (R2=0.96) confirmed that filtration does not affect microbial composition in a sample. For the BC positive samples, the effect of host depletion by filtration increased microbial target reads/million QC reads from 46 reads to 243 reads on average. Microbial reads enrichment by the filter appeared to be more effective for the samples with lower microbial concentration, thus increasing the test sensitivity over mNGS without filter. Using the 2ndBC results as reference, mNGS with filter and mNGS without filter exhibited sensitivities of 81.8% and 63.6%.

Conclusion

The mNGS with filter was able to recover most of the pathogens identified by clinical BC and achieved the highest diagnostic yield. With the clinical implementation to complete the workflow within 24 hours, it has the potential to overcome slow turnaround and low diagnostic yield issues of traditional BC.
Consumer-grade wearables and machine learning sensitively capture disease progression in amyotrophic lateral sclerosis
Authors: Gupta Anoopum S. , Patel Siddharth , Premasiri Alan , Vieira Fernando
Published: March 2023

ALS causes degeneration of motor neurons, resulting in progressive muscle weakness and impairment in fine motor, gross motor, bulbar, and respiratory function. Promising drug development efforts have accelerated in ALS, but are constrained by a lack of objective, sensitive, and accessible outcome measures. Here we investigate the use of consumer-grade wearable sensors, worn on four limbs at home during natural behavior, to quantify motor function and disease progression in 376 individuals with ALS over a several year period. We utilized an analysis approach that automatically detects and characterizes submovements from passively collected accelerometer data and produces a machine-learned severity score for each limb that is independent of clinical ratings. The approach produced interpretable and highly reliable scores that progressed faster than the gold standard ALS Functional Rating Scale-Revised (−0.70 SD/year versus -0.48 SD/year), supporting its use as a sensitive, ecologically valid, and scalable measure for ALS trials and clinical care.
Metabolic network construction reveals probiotic-specific alterations in the metabolic activity of a synthetic small intestinal community
Authors: Jansma Jack , Chatziioannou Anastasia Chrysovalantou , Castricum Kitty , Hemert Saskia van , Aidy Sahar El
Published: March 2023

The gut microbiota plays a crucial role in maintaining overall health and probiotics have emerged as a promising microbiota-targeted therapy for improving human health. However, the molecular mechanisms of probiotics action in general and the targeting of small intestinal microbiota by probiotics are not well understood. To address this, we constructed a synthetic community of three species, which resembles the upper small intestinal microbiota. Our results indicate that probiotic supplementation can directly affect the metabolism of the community, resulting in colonization resistance in a probiotic specific manner. Supplementation withStreptococcus thermophilusled to increased lactate production and a decrease in pH, whileLactobacillus caseisupplementation increased the resistance to perturbations and nutrient utilization without affecting lactate production or pH. Additionally, when combined with kynurenine,Lactobacillus caseienhanced the kynurenine pathway metabolism resulting in elevated kynurenic acid levels and possibly indirect colonization resistance. Overall, our study reveals how selecting probiotics with distinct functional capacities can unlock the full potential of microbiota-targeted therapies.

Importance

The development of probiotic therapies targeted at the small intestinal microbiota represents a significant advancement in the field of probiotic interventions. This region poses unique opportunities due to its low number of gut microbiota, along with the presence of heightened immune and metabolic host responses. However, progress in this area has been hindered by a lack of detailed understanding regarding the molecular mechanisms through which probiotics exert their effects in the small intestine. Our study, utilizing a synthetic community of three small intestinal bacterial strains and the addition of two different probiotic species, and kynurenine as a representative dietary or endogenously produced compound, highlights the importance of selecting probiotic species with diverse genetic capabilities that complement the functional capacity of the resident microbiota, or alternatively, constructing a multispecies formula. This approach holds great promise for the development of effective probiotic therapies and underscores the need to consider the functional capacity of probiotic species when designing interventions.
Optimised protocol for production and analysis of recombinant protein-filled vesicles fromE. coli.
Authors: Streather Bree R. , Baker Karen , Eastwood Tara A. , Mulvihill Daniel P.
Published: March 2023

We have developed an innovative system that exports diverse recombinant proteins in membrane bound vesicles fromE. coli1. These recombinant vesicles compartmentalise proteins within a micro-environment that enables production of otherwise challenging insoluble, toxic, or disulphide-bond containing proteins from bacteria. The release of vesicle-packaged proteins supports isolation from the culture and allows long-term storage of active protein. This technology results in high yields of vesicle-packaged, functional proteins for efficient downstream processing for a wide range of applications from discovery science to applied biotechnology and medicine. In this article, and associated video, we provide a detailed protocol of the method, and highlight key steps in the methodology to maximise recombinant protein filled vesicle production.

This protocol describes a detailed method for the bacterial production of recombinant proteins, including typically insoluble or disulphide-bond containing proteins, packaged inside extracellular membrane-bound vesicles. This has the potential to applied to many areas of scientific research including applied biotechnology and medicine.
Mitochondrial H2O2release does not directly cause genomic DNA damage
Authors: van Soest Daan M.K. , Polderman Paulien E. , den Toom Wytze T. F. , Zwakenberg Susan , de Henau Sasha , Burgering Boudewijn M. T. , Dansen Tobias B.
Published: March 2023

Reactive Oxygen Species (ROS) derived from mitochondrial respiration are frequently cited as a major source of genomic DNA damage and subsequent mutations that contribute to cancer development and aging. However, experimental evidence showing that ROS released by mitochondrial can directly damage nuclear DNA under (patho)physiological conditions has been largely lacking. In this study we modeled the effects of mitochondrial H2O2release and compared this to H2O2production at the nucleosomes in an untransformed human cell line. We used a chemogenetic approach to produce localized H2O2and combined it with a new method we developed to directly quantify the amount of H2O2produced. This enabled us to precisely investigate to what extent DNA damage occurs downstream of near- and supraphysiological amounts of localized H2O2generation. Nuclear H2O2production gives rise to DNA strand breaks, subsequent activation of the DNA damage response, cell cycle arrest and eventually senescence. Release of H2O2from mitochondria on the other hand shows none of these effects, even at levels that are orders of magnitude higher than what mitochondria normally produce. Artificially high levels of mitochondrial H2O2release do result in DNA strand breaks, but in parallel invariably cause ferroptosis-mediated cell death, preventing propagation of DNA damage-induced mutations. This study shows that H2O2released from mitochondria is unlikely to directly damage genomic DNA, limiting its contribution to oncogenic transformation and aging.
Population-level transposable element expression dynamics influence trait evolution in a fungal crop pathogen
Authors: Abraham Leen Nanchira , Oggenfuss Ursula , Croll Daniel
Published: March 2023

Rapid adaptive evolution is driven by strong selection pressure acting on standing genetic variation within populations. How adaptive genetic variation is generated within species and how such variation influences phenotypic trait expression is often not well understood though. Here, we focused on recent activity of transposable elements (TEs) using deep population genomics and transcriptomics analyses of a fungal plant pathogen with a highly active content of TEs in the genome.Zymoseptoria triticicauses one of the most damaging diseases on wheat, with recent adaptation to the host and environment being facilitated by TE-associated mutations. We obtained genomic and RNA-sequencing data from 146 isolates collected from a single wheat field. We established a genome-wide map of TE insertion polymorphisms in the population by analyzing recent TE insertions among individuals. We quantified the locus-specific transcription of individual TEs within the population and revealed considerable variation in transcription across individual TE loci. About 20% of all TE copies show activity in the genome implying that genomic defenses such as repressive epigenetic marks and repeat-induced polymorphisms are ineffective at preventing the proliferation of TEs in the genome. A quarter of recent TE insertions are associated with expression variation of neighboring genes providing broad potential to influence trait expression. We indeed found that TE insertions are likely responsible for variation in virulence on the host and secondary metabolite production. Our study emphasizes how TE-derived polymorphisms segregate even in individual populations and broadly underpin transcription and adaptive trait variation in a species.
Turing pattern prediction in three-dimensional domains: the role of initial conditions and growth
Authors: Ben Tahar Soha , Muñoz Jose J , Shefelbine Sandra J , Comellas Ester
Published: March 2023

Reaction-diffusion systems have been widely used to model pattern formation in biological systems. However, the emergence of Turing patterns in three-dimensional (3D) domains remains relatively unexplored. A few studies on this topic have shown that extending pattern formation from 2D to 3D is not straightforward. Linear stability analysis, which is commonly used to associate admissible wave modes with predicted patterns in 1D and 2D, has yet to be applied in 3D. We have used this approach, together with finite element modelling of a Turing system with Schnakenberg kinetics, to investigate the effects of initial conditions and growing domains on the competition between admissible modes in 3D Turing pattern emergence. Our results reveal that non-random initial conditions on the activator play a stronger role than those of the inhibitor. We also observe a path dependency of the evolving pattern within a growing domain. Our findings shed new light on the mechanisms ensuring reliable pattern formation in 3D domains and have important implications for the development of more robust models of morphogen patterning in developmental processes.
Transposon-sequencing across multiple Mycobacterium abscessus isolates reveals significant functional genomic diversity among strains
Authors: Akusobi Chidiebere , Choudhery Sanjeevani , Benghomari Bouchra S. , Wolf Ian D. , Singhvi Shreya , Ioerger Thomas R. , Rubin Eric J.
Published: March 2023

Mycobacterium abscessus (Mab) is a clinically significant pathogen and a highly genetically diverse species due to its large accessory genome. The functional consequence of this diversity remains unknown mainly because, to date, functional genomic studies in Mab have been primarily performed on reference strains. Given the growing public health threat of Mab infections, understanding the functional genomic differences among Mab clinical isolates can provide more insight into how its genetic diversity influences gene essentiality, clinically relevant phenotypes, and importantly, potential drug targets. To determine the functional genomic diversity among Mab strains, we conducted transposon-sequencing (TnSeq) on 21 genetically diverse clinical isolates, including 15 M. abscessus subsp. abscessus isolates and 6 M. abscessus subsp. massiliense isolates, cataloging all the essential and non-essential genes in each strain. Pan-genome analysis revealed a core set of 3845 genes and a large accessory genome of 11,507. We identified 259 core essential genes across the 21 clinical isolates and 425 differentially required genes, representing ~10% of the Mab core genome. We also identified genes whose requirements were sub-species, lineage, and isolate-specific. Finally, by correlating TnSeq profiles, we identified 19 previously uncharacterized genetic networks in Mab. Altogether, we find that Mab clinical isolates are not only genetically diverse but functionally diverse as well.
The Kinetochore Protein KNL-1 Regulates the Actin Cytoskeleton to Control Dendrite Branching
Authors: Domingos Henrique Alves , Green Mattie , Ouzounidis Vasileios R. , Finlayson Cameron , Prevo Bram , Cheerambathur Dhanya K.
Published: March 2023

The function of the nervous system is intimately tied to its complex and highly inter-connected architecture. Precise control of dendritic branching in individual neurons is central to building the complex structure of the nervous system. Here we show that the kinetochore protein KNL-1 and its associated KMN (Knl1/Mis12/Ndc80 complex) network partners, typically known for their role in chromosome-microtubule coupling during mitosis, control dendrite branching in theC. elegansmechanosensory PVD neuron. KNL-1 restrains excess dendritic branching and promotes contact-dependent repulsion events, ensuring robust sensory behavior and preventing premature neurodegeneration. Unexpectedly, KNL-1 loss resulted in significant alterations of the actin cytoskeleton alongside changes in microtubule dynamics within dendrites. We show that KNL-1 modulates F-actin dynamics to generate proper dendrite architecture, and that its N-terminus can initiate F-actin assembly. These findings reveal that the post-mitotic neuronal KMN network acts to shape the developing nervous system by regulating the actin cytoskeleton and provide new insight into the mechanisms controlling dendrite architecture.
Baicalin Ameliorates Defective Decidualization in URSA by Regulating Mitochondrial Fission Induced Necroptosis
Authors: Zhao Xiaoxuan , Zhao Ying , Yang Qujia , Ma Jing , Zhao Yang , Wang Suxia , Jiang Yuepeng , Zhang Qin
Published: March 2023

Defective decidualization is a significant pathological feature of URSA. And the potential relationship between mitochondrial fission, necroptosis and defective decidualization remains unknown. Baicalin plays an important role in regulating mitochondrial fission and programmed cell death. However, whether baicalin has a protective effect on defective decidualization in URSA has not been reported thus far. This study aims to explore the mechanisms of mitochondrial fission induced necroptosis in defective decidualization in URSA and the regulation of baicalin. First, decidual tissues were collected from URSA and health controls. And then, T-hESC was treated with lipopolysaccharide (LPS), Tyrphostin A9 (TA9), TA9+necrostatin-1(Nec-1) and TA9+baicalin during in vitro decidualization. Besides, URSA mice were established and randomly administrated with low, medium, and high doses of baicalin as well as saline. Results showed that decidualization markers prolactin (PRL) and insulin-like growth factor-binding protein-1 (IGFBP1) in patients with URSA were significantly decreased (P<0.05). The incidence of cell necroptosis was increased, manifested with increased Annexin V and PI positive cells, high level of pRIP3 T231(P<0.01) and pMLKL S358 (P<0.05). Moreover, mitochondrial fission was also hyperactive, featured by elevated level of Fis1 (P<0.01) and Drp1 (P<0.05). In vitro experiments, LPS was induced to trigger necroptosis of T-hESC during induced decidualization, and IGFBP1 and PRL were subsequently decreased (P<0.05). Besides, mitochondrial fission inducer TA9 promoted the level of necroptosis (P<0.05) and induced defective decidualization, which could be rescued by necroptosis inhibitor Nec-1 (P<0.05). In addition, baicalin could reduce mitochondrial fission (P<0.05), necroptosis (P<0.05) and ameliorate defective decidualization in vivo and in vitro (P<0.05). In conclusion, hyperactive mitochondrial fission could promote necroptosis, thus inducing defective decidualization. And baicalin could ameliorates defective decidualization in URSA by regulating mitochondrial fission induced necroptosis.
Statistical examination of shared loci in neuropsychiatric diseases using genome-wide association study summary statistics
Authors: Spargo Thomas P , Gilchrist Lachlan , Hunt Guy P , Dobson Richard JB , Proitsi Petroula , Al-Chalabi Ammar , Pain Oliver , Iacoangeli Alfredo
Published: March 2023

Continued methodological advances have enabled numerous statistical approaches for the analysis of summary statistics from genome-wide association studies. Genetic correlation analysis within specific regions enables a new strategy for identifying pleiotropy. Genomic regions with significant ‘local’ genetic correlations can be investigated further using state-of-the-art methodologies for statistical fine-mapping and variant colocalisation. We explored the utility of a genome-wide local genetic correlation analysis approach for identifying genetic overlaps between the candidate neuropsychiatric disorders, Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and schizophrenia. The correlation analysis identified several associations between traits, the majority of which were loci in the human leukocyte antigen (HLA) region. Colocalisation analysis suggested that disease-implicated variants in these loci often differ between traits and, in one locus, indicated a shared causal variant between amyotrophic lateral sclerosis and Alzheimer’s disease. Our study identified candidate loci that might play a role in multiple neuropsychiatric diseases and suggested the role of distinct mechanisms across diseases despite shared loci. The fine-mapping and colocalisation analysis protocol designed for this study has been implemented in a flexible analysis pipeline that produces HTML reports and is available at:https://github.com/ThomasPSpargo/COLOC-reporter.
Characterisation of the SUF FeS cluster machinery in the amitochondriate eukaryoteMonocercomonoides exilis
Authors: Peña-Diaz Priscila , Braymer Joseph J. , Vacek Vojtěch , Zelená Marie , Lometto Stefano , Hrdý Ivan , Treitli Sebastian C. , Hochberg Georg , Py Béatrice , Lill Roland , Hampl Vladimír
Published: March 2023

Monocercomonoides exilisis the first eukaryotic organism described as a complete amitochondriate, yet it shares common features with heterotrophic anaerobic/microaerophilic protists, some of which bear divergent mitochondrion-related organelles or MROs. It has been postulated that the retention of these organelles stems from their involvement in the assembly of essential cytosolic and nuclear FeS proteins, whose maturation requires the evolutionarily conserved mitochondrial ISC and cytosolic CIA machineries. The amitochondriateM. exilislacks genes encoding the ISC machinery yet contains a bacteria-derived SUF system (MeSuf), composed of the cysteine desulphurase SufS fused to SufD and SufU, as well as the FeS scaffolding components MeSufB and MeSufC. Here, we show that expression of the M. exilis SUFgenes, either individually or in tandem, can restore the maturation of the FeS protein IscR in theEscherichia colidouble mutants of ΔsufSΔiscSand ΔsufBΔiscUA. In vivoandin vitrostudies indicate that purified MeSufB, MeSufC and MeSufDSU proteins interact suggesting that they act as a complex in the protist. MeSufBC can undergo conformational changes in the presence of ATP and assemble FeS clusters under anaerobic conditions in presence and absence of ATPin vitro. Altogether, these results indicate that the dynamically interacting MeSufDSUBC proteins may function as an FeS cluster assembly complex inM. exilisthereby being capable of replacing the organelle-enclosed ISC system of canonical eukaryotes.
The X-ray crystallography phase problem solved thanks to AlphaFold and RoseTTAFold models: a case-study report. Corrigendum
Authors: Barbarin-Bocahu Irène , Graille Marc
Published: March 2023

A figure in the article by Barbarin-Bocahu & Graille [(2022), Acta Cryst. D78, 517–531] is corrected.
Green innovation and the cost of equity: evidence from China
Authors: Alkebsee Radwan , Habib Ahsan , Li Junyan
Published: March 2023

Purpose

This paper aims to examine the association between green innovation and the cost of equity in China. This study relies on the investors’ base perspective and shareholders’ perceived risk perspective to investigate the relation between green innovation and the cost of equity in China.

Design/methodology/approach

The paper uses firm-fixed effect regression for a sample of Chinese public companies for the period 2008–2018.

Findings

The authors find a negative relationship between green innovation and the cost of equity capital. This negative association is found to be more pronounced for less financially constrained firms, during periods of high economic policy uncertainty, and for firms with a strong internal control environment. Finally, the paper shows that the negative association became more pronounced after the passage of the Environmental Protection Law of China in 2012. The results remain robust to possible endogeneity concerns.

Originality/value

This study contributes to the green innovation literature by documenting that shareholders favorably view firms implementing green innovation policies. The study also has policy implications for Chinese regulators in improving the green credit policy.
Does personal data protection matter for ISO 9001 certification and firm performance?
Authors: Siougle Efrosini , Dimelis Sophia , Malevris Nikolaos
Published: March 2023

Purpose

This study explores the link between ISO 9001 certification, personal data protection and firm performance using financial balance sheet and survey data. The security aspect of data protection is analyzed based on the major requirements of the General Data Protection Regulation and mapped to the relevant controls of the ISO/IEC 27001/27002 standards.

Design/methodology/approach

The research analysis is based on 96 ISO 9001–certified and non-certified publicly traded manufacturing and service firms that responded to a structured questionnaire. The authors develop and empirically test their theoretical model using the structural equation modeling technique and follow a difference-in-differences econometric modeling approach to estimate financial performance differences between certified and non-certified firms accounting for the level of data protection.

Findings

The estimates indicate three core dimensions in the areas of “policies, procedures and responsibilities,” “access control management” and “risk-reduction techniques” as desirable components in establishing the concept of data security. The estimates also suggest that the data protection level has significantly impacted the performance of certified firms relative to the non-certified. Controlling for the effect of industry-level factors reveals a positive relationship between data security and high-technological intensity.

Practical implications

The results imply that improving the level of compliance to data protection enhances the link between certification and firm performance.

Originality/value

This study fills a gap in the literature by empirically testing the influence of data protection on the relationship between quality certification and firm performance.
Collation of best practices for preparedness: lessons from disasters in Pakistan and Japan
Authors: Schwarz Jonas , Kascel Valentina , Azmat Muhammad , Kummer Sebastian
Published: March 2023

Purpose

This study aims to compare the humanitarian supply chains and logistics of two countries in earthquake preparedness by modifying and using a previously established preparedness evaluation framework.

Design/methodology/approach

A European flood emergency management system (FEMS) is a seven-dimensional framework to assess a country’s preparedness for flood emergencies. The FEMS framework was modified to apply to earthquakes. Leveraging a multiple explanatory case study approach with data analysis, the authors reconstructed the events of the earthquakes in Pakistan (2005) and Japan (2011) with an applied grading (1–5). Findings were evaluated within the adopted FEMS framework. From a practitioner’s perspective, the framework is applicable and can accelerate support in the field.

Findings

Pakistan lacked emergency plans before the 2005 earthquake. In contrast, Japan possessed emergency plans before the disaster, helping minimise casualties. Overall, Japan demonstrated considerably better emergency management effectiveness. However, both countries significantly lacked the distribution of responsibilities among actors.

Originality/value

Practical factors in the humanitarian supply chain are well understood. However, synthesising individual factors into a comprehensive framework is difficult, which the study solves by applying and adopting the FEMS framework to earthquakes. The developed framework allows practitioners a structured baseline for prioritising measures in the field. Furthermore, this study exemplifies the usefulness of cross-hazard research within emergency management and preparedness in a real-world scenario.
How store attribute affects customer experience, brand love and brand loyalty
Authors: Anggara Ahmad Khabib Dwi , Ratnasari Ririn Tri , Osman Ismah
Published: March 2023

Purpose

This study aims to determine the influence of store attributes on customer experience, brand love and brand loyalty at Hijup stores.

Design/methodology/approach

This research uses quantitative methods. The technique of determining the sample used is purposive sampling. The sample criteria in this study were consumers who had visited and bought products directly at the Hijup store with a minimum age of 17 years. The amount of data collected is 224 samples. Data was collected by distributing online questionnaires. The data analysis technique used the structural equation modeling operated through the IBM AMOS 26.0 program.

Findings

The results of the study reveal that customer experience is influenced by all dimensions of the store attribute variable including merchandise, communication with staff, store atmosphere and transaction convenience. In addition, this study shows that customer experience also positively affects brand love and brand loyalty. Finally, the analysis shows that brand love positively affects brand loyalty.

Research limitations/implications

The theoretical contribution of this research is the testing of four variables (store attribute, customer experience, brand love and brand loyalty) in the same model in the context of halal fashion, thus helping to broaden insight and understanding of the influence of store attributes on customer experience, brand love and brand loyalty in halal fashion. This research can be a reference for academics to develop further research following this research topic.

Practical implications

This study provides practical implications for managers to increase their efforts in creating good store attributes, to create a positive customer experience that can build customer brand love and brand loyalty.

Social implications

The long-term effect of the company’s success in developing brand love and brand loyalty is that it makes it easier for customers to trust, be satisfied and recommend the brand to others.

Originality/value

In the context of the halal concept, several studies among Muslims in Asia and western countries have yielded important information about consumer behavior toward halal products such as food and tourism. Departing from previous research, this research is to fill the gaps of previous research and get better insights into the customer experience visiting halal fashion stores. Therefore, this study tries to define and validate consumer profiles about halal fashion and identify customer experience, brand loyalty and brand love in the context of halal fashion.
Unleashing open innovation in the public sector: a bibliometric and interpretive literature review
Authors: Palumbo Rocco , Casprini Elena , Fakhar Manesh Mohammad
Published: March 2023

Purpose

Institutional, economic, social and technological advancements enable openness to cope with wicked public management issues. Although open innovation (OI) is becoming a new normality for public sector entities, scholarly knowledge on this topic is not fully systematized. The article fills this gap, providing a thick and integrative account of OI to inspire public management decisions.

Design/methodology/approach

Following the SPAR-4-SLR protocol, a domain-based literature review has been accomplished. Consistently with the study purpose, a hybrid methodology has been designed. Bibliographic coupling permitted us to discover the research streams populating the scientific debate. The core arguments addressed within and across the streams were reported through an interpretive approach.

Findings

Starting from an intellectual core of 94 contributions, 5 research streams were spotted. OI in the public sector unfolds through an evolutionary path. Public sector entities conventionally acted as “senior partners” of privately-owned companies, providing funding (yellow cluster) and data (purple cluster) to nurture OI. An advanced perspective envisages OI as a public management model purposefully enacted by public sector entities to co-create value with relevant stakeholders (red cluster). Fitting architectures (green cluster) and mechanisms (blue cluster) should be arranged to release the potential of OI in the public sector.

Research limitations/implications

The role of public sector entities in enacting OI should be revised embracing a value co-creation perspective. Tailored organizational interventions and management decisions are required to make OI a reliable and dependable public value generation model.

Originality/value

The article originally systematizes the scholarly knowledge about OI, presenting it as a new normality for public value generation.
Continuous cultivation of the lithoautotrophic nitrate‐reducing Fe(II)‐oxidizing culture KS in a chemostat bioreactor
Authors: Bayer Timm , Tomaszewski Elizabeth J. , Bryce Casey , Kappler Andreas , Byrne James M.
Published: March 2023

Laboratory‐based studies on microbial Fe(II) oxidation are commonly performed for 5–10 days in small volumes with high substrate concentrations, resulting in geochemical gradients and volumetric effects caused by sampling. We used a chemostat to enable uninterrupted supply of medium and investigated autotrophic nitrate‐reducing Fe(II)‐oxidizing culture KS for 24 days. We analysed Fe‐ and N‐speciation, cell‐mineral associations, and the identity of minerals. Results were compared to batch systems (50 and 700 mL—static/shaken). The Fe(II) oxidation rate was highest in the chemostat with 7.57 mM Fe(II) d−1, while the extent of oxidation was similar to the other experimental setups (average oxidation of 92% of all Fe(II)). Short‐range ordered Fe(III) phases, presumably ferrihydrite, precipitated and later goethite was detected in the chemostat. The 1 mM solid phase Fe(II) remained in the chemostat, up to 15 μM of reactive nitrite was measured, and 42% of visualized cells were partially or completely mineral‐encrusted, likely caused by abiotic oxidation of Fe(II) by nitrite. Despite (partial) encrustation, cells were still viable. Our results show that even with similar oxidation rates as in batch cultures, cultivating Fe(II)‐oxidizing microorganisms under continuous conditions reveals the importance of reactive nitrogen intermediates on Fe(II) oxidation, mineral formation and cell–mineral interactions.
The impact of treatment resistance on outcome and course of electroconvulsive therapy in major depressive disorder
Authors: Rovers J. J. E. , Vissers P. , Loef D. , van Waarde J. A. , Verdijk J. P. A. J. , Broekman B. F. P. , Vergouwen A. C. M. , Oudega M. L. , van Exel E. , Coenen R. , Everaerd D. S. , Tendolkar I. , Dols A. , van Eijndhoven P. F. P.
Published: March 2023

Introduction

Major depressive disorder (MDD) is a common psychiatric disorder. Despite several treatment options, a subgroup of patients will not respond to the commonly used antidepressant treatments and thus express treatment resistance (TRD). TRD can be quantified with the Dutch Measure for Treatment Resistance in Depression (DM‐TRD). Electroconvulsive therapy (ECT) is an effective treatment for MDD, also in TRD. Yet, the position of ECT as “treatment‐of‐last‐resort” may decrease the likelihood of beneficial outcome. Our aim was to investigate the association between treatment resistance and outcome and course of ECT.

Methods

We performed a retrospective, multicenter cohort study with 440 patients of which data was retrieved from patient records as collected in the Dutch ECT Cohort database. Linear and logistic regression models were used to explore the association between level of treatment resistance and outcome of ECT. Median split was used to explore the differences between high and low level of TRD and course of treatment.

Results

A higher DM‐TRD score was associated with significantly smaller reduction of depression symptoms (R2 = 0.160; β = −2.968; p < 0.001) and lower chance of response (OR = 0.821 [95 CI: 0.760–0.888]; β = −0.197; p < 0.001). Low level TRD patients underwent fewer ECT sessions (mean 13 ± 6 SD vs. 16 ± 7 SD; p < 0.001) and fewer switches from right unilateral tot bifrontotemporal electrode placement (29% vs. 40%; p = 0.032).

Conclusion

Reserving ECT as “treatment‐of‐last‐resort” in the treatment algorithm for MDD seems questionable, because in our study lower level of treatment resistance predicted more beneficial ECT‐outcome. Moreover, providing ECT in less treatment resistant patients showed fewer needed ECT‐sessions and less switches to BL electrode placement, which may decrease the risk for cognitive side‐effects.
Splanchnic vein thrombosis in acute pancreatitis: a review of treatment indications, methods, and outcomes in a single institution
Authors: Wilson Tamalee M. , Daneshmand Ali , Parys Simon , Watanabe Yuki
Published: March 2023

Background

Splanchnic vein thrombosis (SVT) is a well‐recognized complication of acute pancreatitis. The question of whether or not to treat SVT with systemic therapeutic anticoagulation (STA) remains to be seen. The universal use of anticoagulation may lead to an increased risk of bleeding complications associated with acute pancreatitis. Literature on this subject is sparse and there is no clear guideline on how to treat SVT. Our research demonstrates local practice where therapeutic anticoagulation in SVT varies.

Methods

A retrospective review of patients presenting with acute pancreatitis admitted over a five‐year period to a single tertiary hospital with splanchnic vein thrombosis was performed.

Results

Of the 1408 patients admitted with acute pancreatitis, 42 were diagnosed with splanchnic vein thrombosis, with a male dominance of 34 (81%). A total of 25 patients received anticoagulation. The use of anticoagulation was dependent on the location of the thrombus, P < 0.01. Anticoagulation use was most common in cases of combination mesenteric, splenic, and portal vein thrombus (100%), isolated mesenteric vein (100%), isolated portal vein (89%), combination portal and splenic vein (87%), and combination mesenteric and splenic vein (75%). The rate of anticoagulation use was lowest in isolated splenic vein thrombus (23%).

Conclusion

The early commencement of STA in patients with acute pancreatitis and triple‐vessel SVT or with portal vein involvement is supported by our data. Isolated splenic vein thrombus does not require systemic therapy. Further research is needed to establish a clear clinical guideline.