bluuebunny/crossref_metadata_2025 huggingface dataset:
Deployment of aVibrio choleraeordered transposon mutant library in a quorum-competent genetic background
Authors: Grant Nkrumah A. , Donkor Gracious Yoofi , Sontz Jordan T. , Soto William , Waters Christopher M.
Published: November 2023

Vibrio cholerae, the causative agent of cholera, has sparked seven pandemics in recent centuries, with the current one being the most prolonged.V. cholerae’spathogenesis hinges on its ability to switch between low and high cell density gene regulatory states, enabling transmission between host and the environment. Previously, a transposon mutant library forV. choleraewas created to support investigations aimed toward uncovering the genetic determinants of its pathogenesis. However, subsequent sequencing uncovered a mutation in the geneluxOof the parent strain, rendering mutants unable to exhibit high cell density behaviors. In this study, we used chitin-independent natural transformation to move transposon insertions from these low cell density mutants into a wildtype genomic background. Library transfer was aided by a novel gDNA extraction we developed using thymol, which also showed high lysis-specificity forVibrio. The resulting Grant Library comprises 3,102 unique transposon mutants, covering 79.8% ofV. cholerae’sopen reading frames. Whole genome sequencing of randomly selected mutants demonstrates 100% precision in transposon transfer to cognate genomic positions of the recipient strain. Notably, in no instance did theluxOmutation transfer into the wildtype background. Our research uncovered density-dependent epistasis in growth on inosine, an immunomodulatory metabolite secreted by gut bacteria that is implicated in enhancing gut barrier functions. Additionally, Grant Library mutants retain the plasmid that enables rapid, scarless genomic editing. In summary, the Grant Library reintroduces organismal relevant genetic contexts absent in the low cell density locked library equivalent.

Significance Statement

Ordered transposon mutant libraries are essential tools for catalyzing research by providing access to null mutants of all non-essential genes. Such a library was previously generated forVibrio cholerae, but whole genome sequencing revealed that this library was made using a parent strain that is unable to exhibit cell-cell communication known as quorum sensing. Here, we utilize natural competence combined with a novel, high-throughput genomic DNA extraction method to regenerate the signaling incompetentV. choleraeordered transposon mutant library in quorum sensing competent strain. Our library provides researchers with a powerful tool to understandV. choleraebiology within a genetic context that influences how it transitions from an environmentally benign organism to a disease-causing pathogen.
The N6-methyladenosine demethylase ALKBH5 regulates the hypoxic HBV transcriptome
Authors: Tsukuda Senko , Harris James M , Magri Andrea , Balfe Peter , Wing Peter AC , Siddiqui Aleem , McKeating Jane A
Published: November 2023

Chronic hepatitis B is a global health problem and current treatments only suppress hepatitis B virus (HBV) infection, highlighting the need for new curative treatments. Oxygen levels influence HBV replication and we previously reported that hypoxia inducible factors (HIFs) activate the basal core promoter to transcribe pre-genomic RNA. Application of a probe-enriched long-read sequencing method to map the HBV transcriptome showed an increased abundance of all viral RNAs under low oxygen or hypoxic conditions. Importantly, the hypoxic-associated increase in HBV transcripts was dependent on N6-methyladenosine (m6A) modifications and an m6A DRACH motif in the 5’ stem loop of pre-genomic RNA defined transcript half-life under hypoxic conditions. Given the essential role of m6A modifications in the viral transcriptome we assessed the oxygen-dependent expression of RNA demethylases and bio-informatic analysis of published single cell RNA-seq of murine liver showed an increased expression of the RNA demethylase ALKBH5 in the peri-central low oxygen region.In vitrostudies with a human hepatocyte derived HepG2 cell line showed increased ALKBH5 gene expression under hypoxic conditions. Silencing the demethylase reduced the levels of HBV pre-genomic RNA and host gene (CA9, NDRG1, VEGFA, BNIP3, FUT11, GAP and P4HA1) transcripts and this was mediated via reduced HIFα expression. In summary, our study highlights a previously unrecognized role for ALKBH5 in orchestrating viral and cellular transcriptional responses to low oxygen.

Author Summary

Oxygen levels influence HBV replication and hypoxia inducible factors (HIFs) activate HBV transcription. Long-read sequencing and mapping the HBV transcriptome showed an increased abundance of all viral RNAs under hypoxic conditions that was dependent on N6-methyladenosine modifications. Investigating the oxygen-dependent expression of RNA demethylases identified ALKBH5 as a hypoxic activated gene and silencing its expression showed a key role in regulating HBV and host gene expression under hypoxic conditions.
Bioremediation of Atrazine and its Metabolite Using Multiple Enzymes Delivered by aBacillus thuringiensisSpore Display System
Authors: Hsu Shu-Yu , Hsieh Hsin-Yeh , Stewart George C. , Lin Chung-Ho
Published: November 2023

Atrazine (ATR), a widely used herbicide in the United States, has contaminated ground and surface water. The persistence in the environment, the carcinogenic characteristic, and the endocrine disruption activity of ATR raises public health concerns. To provide a clean source of drinking water, it is imperative to remediate ATR and its metabolites without toxic by-products. A green technology,Bacillus thuringiensisspore-based display system, has been developed to express a high density of enzymes on the spore surface. TheB. thuringiensisspore can serve as a bioparticle to deliver enzymes to different environments and enhance the stability and shelf-life of enzymes expressed on their surface. A cluster of enzymes, AtzA, AtzB, AtzC, AtzD, AtzE, and AtzF, found inPseudomonas sp.strain ADP, remediates ATR to CO2and NH3in the degradation pathway. AtzA-bearing spores were generated, and they successfully demonstrated the capability of converting ATR to its metabolite, hydroxyatrazine (HA) [Hsiehet al.2020]. In this study, AtzB, a hydroxyatrazineN-ethylaminohydrolase that hydrolyzes HA toN-isopropylammelide (NiPA), was expressed on theBacillusspores by fusingatzBto the gene encoding the attachment domain of the BclA spore surface nap layer protein. The results showed that 1 mg AtzB-bearing spores degraded 50% of HA to NiPA in water within 12 hours. The Kmand Vmaxof AtzB-bearing spores with HA as a substrate were 25.28 µM and 1.26 nmole NiPA h-1mg-1spores, respectively. The optimal ratio of 1:2 for AtzA-bearing to AtzB-bearing spores was applied and successfully converted 90% ATR to NiPA in the water after 96 hours of incubation. The surface water with the addition of 34.5 nM (7.5 µg L-1) of ATR was treated with a combination of AtzA-bearing and AtzB-bearing spores in a 96-hour time course study. Over 80% of applied ATR in surface water was degraded and ATR concentration was below the United States Environmental Protection Agency maximum contaminant level, 13.8 nM (3 µg L-1) within 24 hours. At the end of 96 hours. ATR in surface water was completely converted to NiPA. We have successfully demonstrated the application of multienzyme bioremediation of ATR using theBacillusspore-based display system in the surface water in the laboratory.
Covalent Degrader of the Oncogenic Transcription Factor β-Catenin
Authors: Gowans Flor A. , Forte Nafsika , Hatcher Justin , Huang Oscar W. , Wang Yangzhi , Poblano Belen E. Altamirano , Wertz Ingrid E. , Nomura Daniel K.
Published: November 2023

β-catenin (CTNNB1) is an oncogenic transcription factor that is important in cell-cell adhesion and transcription of cell proliferation and survival genes that drives the pathogenesis of many different types of cancers. However, direct pharmacological targeting of CTNNB1 has remained challenging deeming this transcription factor as “undruggable.” Here, we have performed a screen with a library of cysteine-reactive covalent ligands to identify a monovalent degrader EN83 that depletes CTNNB1 in a ubiquitin-proteasome-dependent manner. We show that EN83 directly and covalently targets CTNNB1 through targeting four distinct cysteines within the armadillo repeat domain—C439, C466, C520, and C619—leading to a destabilization of CTNNB1. Using covalent chemoproteomic approaches, we show that EN83 directly engages CTNNB1 in cells with a moderate degree of selectivity. We further demonstrate that direct covalent targeting of three of these four cysteines--C466, C520, and C619--in cells contributes to CTNNB1 degradation in cells. We also demonstrate that EN83 can be further optimized to yield more potent CTNNB1 binders and degraders. Our results show that chemoproteomic approaches can be used to covalently target and degrade challenging transcription factors like CTNNB1 through a destabilization-mediated degradation.
Development ofCorynebacterium glutamicumas a monoterpene production platform
Authors: Luckie Bridget A. , Kashyap Meera , Pearson Allison N. , Chen Yan , Liu Yuzhong , Valencia Luis E. , Romero Alexander Carrillo , Hudson Graham A. , Tao Xavier B. , Wu Bryan , Petzold Christopher J. , Keasling Jay D.
Published: November 2023

Monoterpenes are commonly known for their role in the flavors and fragrances industry and are also gaining attention for other uses like insect repellant and as potential renewable fuels for aviation.Corynebacterium glutamicum,a Generally Recognized as Safe microbe, has been a choice organism in industry for the annual million ton-scale bioproduction of amino acids for more than 50 years; however, efforts to produce monoterpenes inC. glutamicumhave remained relatively limited. In this study, we report a further expansion of theC. glutamicumbiosynthetic repertoire through the development and optimization of a mevalonate-based monoterpene platform. In the course of our plasmid design iterations, we increased flux through the mevalonate-based bypass pathway, measuring isoprenol production as a proxy for monoterpene precursor abundance and demonstrating the highest reported titers inC. glutamicumto date at nearly 1500 mg/L. Our designs also evaluated the effects of backbone, promoter, and GPP synthase homolog origin on monoterpene product titers. Monoterpene production was further improved by disrupting competing pathways for isoprenoid precursor supply and by implementing a biphasic production system to prevent volatilization. With this platform, we achieved 321.1 mg/L of geranoids, 723.6 mg/L of 1,8-cineole, and 227.8 mg/L of linalool. Furthermore, we determined thatC. glutamicumfirst oxidizes geraniol through an aldehyde intermediate before it is asymmetrically reduced to citronellol. Additionally, we demonstrate that the aldehyde reductase, AdhC, possesses additional substrate promiscuity for acyclic monoterpene aldehydes.

Highlights

Design of a mevalonate-based monoterpene production platform inC. glutamicum

Highest production titers of geranoids, eucalyptol, and linalool reported inC. glutamicumto date

Identification of citronellal as an intermediate in the reduction of geraniol to citronellol byC. glutamicum
Queuosine biosynthetic enzyme, QueE moonlights as a cell division regulator
Authors: Adeleye Samuel A. , Yadavalli Srujana S.
Published: November 2023

In many organisms, stress responses to adverse environments can trigger secondary functions of certain proteins by altering protein levels, localization, activity, or interaction partners.Escherichia colicells respond to the presence of specific cationic antimicrobial peptides by strongly activating the PhoQ/PhoP two-component signaling system, which regulates genes important for growth under this stress. As part of this pathway, a biosynthetic enzyme called QueE, which catalyzes a step in the formation of queuosine (Q) tRNA modification is upregulated. When cellular QueE levels are high, it co-localizes with the central cell division protein FtsZ at the septal site, blocking division and resulting in filamentous growth. Here we show that QueE affects cell size in a dose-dependent manner. Using alanine scanning mutagenesis of amino acids in the catalytic active site, we pinpoint particular residues in QueE that contribute distinctly to each of its functions – Q biosynthesis or regulation of cell division, establishing QueE as a moonlighting protein. We further show that QueE orthologs from enterobacteria likeSalmonella typhimuriumandKlebsiella pneumoniaealso cause filamentation in these organisms, but the more distant counterparts fromPseudomonas aeruginosaandBacillus subtilislack this ability. By comparative analysis ofE. coliQueE with distant orthologs, we elucidate a unique region in this protein that is responsible for QueE’s secondary function as a cell division regulator. A dual-function protein like QueE is an exception to the conventional model of “one gene, one enzyme, one function”, which has divergent roles across a range of fundamental cellular processes including RNA modification and translation to cell division and stress response.

Author Summary

In stressful environments, proteins in many organisms can take on extra roles. WhenEscherichia colibacteria are exposed to antimicrobial compounds, the cell activates the PhoQ/PhoP signaling system, increasing the production of an enzyme called QueE. QueE is usually involved in the formation of queuosine (Q) tRNA modification. When cells make abundant QueE, it interacts with a vital division protein, FtsZ, disrupting division and causing elongation − a “moonlighting” function. Detailed study of QueE reveals specific regions involved in Q biosynthesis or cell division. QueE in organisms closely related toE. colialso has dual roles, while distant relatives are unifunctional. Comparative analysis identifies a uniqueE. coliQueE region regulating cell division. This study shows QueE’s versatility in linking and impacting distinct cellular processes such as RNA metabolism, protein translation, cell division, and stress response.
NK and NKT cells in the pathogenesis of Hidradenitis suppurativa: Novel therapeutic strategy through targeting of CD2
Authors: Kashyap Mahendra P. , Mishra Bharat , Sinha Rajesh , Jin Lin , Kumar Nilesh , Goliwas Kayla F. , Deshane Jessy , Elewski Boni E. , Elmets Craig A. , Athar Mohammad , Shahid Mukhtar M. , Raman Chander
Published: November 2023

Hidradenitis suppurativa (HS) is a chronic debilitating inflammatory skin disease with poorly understood pathogenesis. Single-cell RNAseq analysis of HS lesional and healthy individual skins revealed that NKT and NK cell populations were greatly expanded in HS, and they expressed elevated CD2, an activation receptor. Immunohistochemistry analyses confirmed significantly expanded numbers of CD2+ cells distributed throughout HS lesional tissue, and many co-expressed the NK marker, CD56. While CD4+ T cells were expanded in HS, CD8 T cells were rare. CD20+ B cells in HS were localized within tertiary follicle like structures. Immunofluorescence microscopy showed that NK cells (CD2+CD56dim) expressing perforin, granzymes A and B were enriched within the hyperplastic follicular epidermis and tunnels of HS and juxtaposed with apoptotic cells. In contrast, NKT cells (CD2+CD3+CD56bright) primarily expressed granzyme A and were associated with α-SMA expressing fibroblasts within the fibrotic regions of the hypodermis. Keratinocytes and fibroblasts expressed high levels of CD58 (CD2 ligand) and they interacted with CD2 expressing NKT and NK cells. The NKT/NK maturation and activating cytokines, IL-12, IL-15 and IL-18, were significantly elevated in HS. Inhibition of cognate CD2-CD58 interaction with blocking anti-CD2 mAb in HS skin organotypic cultures resulted in a profound reduction of the inflammatory gene signature and secretion of inflammatory cytokines and chemokines in the culture supernate. In summary, we show that a cellular network of heterogenous NKT and NK cell populations drives inflammation, tunnel formation and fibrosis in the pathogenesis of HS. Furthermore, CD2 blockade is a viable immunotherapeutic approach for the management of HS.
Mass media campaigns and the ‘file drawer problem’: a Delphi study of how to avoid campaign failure
Authors: Kite James , Thomas Margaret , Bellew Bill , Bauman Adrian , Grunseit Anne
Published: November 2023

Mass media campaigns are frequently used to address public health issues. Considering the considerable cost, there has been surprisingly little analysis of why campaigns sometimes fail. This study used a modified Delphi approach to explore the mechanisms that can lead to failure and to identify what can be done to avoid or overcome common mistakes in campaign planning, implementation, and evaluation. Through interviews and a survey with 28 public health social marketing and mass media campaign experts, we identified four systemic factors that drive success: long-term strategic thinking and commitment, understanding the campaign context, doing and learning from evaluation, and fostering strong relationships. The factors did not operate in isolation, rather good (or poor) execution in one area was likely to influence performance in another. The experts also emphasised that a change of political context could drastically affect one or more of the identified factors. Our analysis showed that campaign failures are not simply individuals making mistakes. Systemic issues throughout the planning, execution, and evaluation phases need to be addressed if campaign outcomes are to improve.
Linking the genetic structure of neuroanatomical phenotypes with psychiatric disorders
Authors: Auvergne Antoine , Traut Nicolas , Henches Léo , Troubat Lucie , Frouin Arthur , Boetto Christophe , Kazem Sayeh , Julienne Hanna , Toro Roberto , Aschard Hugues
Published: November 2023

There is increasing evidence of shared genetic factors between psychiatric disorders and brain magnetic resonance imaging (MRI) phenotypes. However, deciphering the joint genetic architecture of these outcomes has proven challenging, and new approaches are needed to infer potential genetic structure underlying those phenotypes. Here, we demonstrate how multivariate analyses can help reveal links between MRI phenotypes and psychiatric disorders missed by univariate approaches. We first conducted univariate and multivariate genome-wide association studies (GWAS) for eight MRI-derived brain volume phenotypes in 20K UK Biobank participants. We performed various enrichment analyses to assess whether and how univariate and multitrait approaches can distinguish disorder-associated and non-disorder-associated variants from six psychiatric disorders: bipolarity, attention-deficit/hyperactivity disorder (ADHD), autism, schizophrenia, obsessive-compulsive disorder, and major depressive disorder. Univariate MRI GWAS displayed only negligible genetic correlation with psychiatric disorders at all the levels we investigated. Multitrait GWAS identified multiple new associations and showed significant enrichment for variants related to both ADHD and schizophrenia. We further clustered top associated variants based on their MRI multitrait association using an optimizedk-medoids approach and detected two clusters displaying not only enrichment for association with ADHD and schizophrenia, but also consistent direction of effects. Functional annotation analyses pointed to multiple potential mechanisms, suggesting in particular a role of neurotrophin pathways on both MRI and schizophrenia. Altogether our results show that multitrait association signature can be used to infer genetically-driven latent MRI variables associated with psychiatric disorders, opening paths for future biomarker development.
High-resolution comparative atomic structures of two Giardiavirus prototypes infectingG. duodenalisparasite
Authors: Wang Han , Gianluca Marucci , Munke Anna , Hassan Mohammad Maruf , Lalle Marco , Okamoto Kenta
Published: November 2023

Giardia lamblia virus(GLV) is a non-enveloped icosahedral dsRNA virus and an endosymbiont virus infecting the zoonotic protozoan parasiteGiardia duodenalis(syn.G. lamblia, G. intestinalis), a pathogen of mammals, including humans. Elucidating the transmission mechanism of GLV is crucial to an in-depth understanding of the virulence of the virus inG. duodenalis. GLV belongs to the familyTotiviridae,which infects yeast and protozoa intracellularly; however, it also transmits extracellularly, similar to phylogenetically distantly related toti-like viruses that infect multicellular hosts. The GLV capsid structure is extensively involved in the longstanding discussion concerning the acquisition of extracellular transmission inTotiviridaeand toti-like viruses. Hence, this study constructed the first high-resolution comparative atomic models of two GLV strains, namely GLV-HP and GLV-CAT, which showed different intracellular localization and virulence phenotypes, using cryo-EM single-particle analysis. The atomic models of the GLV capsids presented swapped C-terminal extensions, extra surface loops, and a lack of cap-snatching pockets, similar to those of toti-like viruses. However, their open pores and lack of the extra crown protein (CrP) resemble those of other yeast and protozoanTotiviridaeviruses, demonstrating the essential structures for acquiring extracellular cell-to-cell transmission. The intensive structural comparison between GLV-HP and GLV-CAT indicates the first evidence of critical structural motifs for the transmission and virulence of GLV inG. duodenalis.
The shared genetic architecture and evolution of human language and musical rhythm
Authors: Alagöz Gökberk , Eising Else , Mekki Yasmina , Bignardi Giacomo , Fontanillas Pierre ,   23andMe Research Team, Nivard Michel G. , Luciano Michelle , Cox Nancy J. , Fisher Simon E. , Gordon Reyna L.
Published: November 2023

Rhythm and language-related traits are phenotypically correlated, but their genetic overlap is largely unknown. Here, we leveraged two large-scale genome-wide association studies performed to shed light on the shared genetics of rhythm (N=606,825) and dyslexia (N=1,138,870). Our results reveal an intricate shared genetic and neurobiological architecture, and lay groundwork for resolving longstanding debates about the potential co-evolution of human language and musical traits.
Incorporation of 5 methylcytidine alleviates innate immune response to self-amplifying RNA vaccine
Authors: Komori Mai , Morey Amber L. , Quiñones-Molina Andrés A. , Fofana Josiane , Romero Luis , Peters Elizabeth , Matsuda Kenta , Gummuluru Suryaram , Smith Jonathan F. , Akahata Wataru , Akiyama Hisashi
Published: November 2023

In order to improve vaccine effectiveness and safety profile of existing synthetic RNA-based vaccines, we have developed a self-amplifying RNA (saRNA)-based vaccine expressing membrane-anchored receptor binding domain (RBD) of SARS-CoV-2 S protein (S-RBD) and have demonstrated that a minimal dose of this saRNA vaccine elicits robust immune responses. Results from a recent clinical trial with 5-methylcytidine (5mC) incorporating saRNA vaccine demonstrated reduced vaccine-induced adverse effects while maintaining robust humoral responses. In this study, we investigate the mechanisms accounting for induction of efficient innate and adaptive immune responses and attenuated adverse effects induced by the 5mC-incorporated saRNA. We show that the 5mC-incorporating saRNA platform leads to prolonged and robust expression of antigen, while induction of type-I interferon (IFN-I), a key driver of reactogenicity, is attenuated in peripheral blood mononuclear cells (PBMCs), but not in macrophages and dendritic cells. Interestingly, we find that the major cellular source of IFN-I production in PBMCs is plasmacytoid dendritic cells (pDCs), which is attenuated upon 5mC incorporation in saRNA. In addition, we demonstrate that monocytes also play an important role in amplifying proinflammatory responses. Furthermore, we show that the detection of saRNA is mediated by a host cytosolic RNA sensor, RIG-I. Importantly, 5mC-incorporating saRNA vaccine candidate produced robust IgG responses against S-RBD upon injection in mice, thus providing strong support for the potential clinical use of 5mC-incorporating saRNA vaccines.
Characterisation of ligand gating, ion conduction and the ion selectivity mechanism in the endo-lysosomal ion channel hTPC2
Authors: Şahin Alp Tegin , Zachariae Ulrich
Published: November 2023

Two pore channels (TPCs) are two-fold symmetric endo-lysosomal cation channels forming important drug targets especially for antiviral drugs. They are activated by calcium, ligand binding, and membrane voltage, and to date, are the only ion channels shown to alter their ion selectivity depending on the type of bound ligand. However, despite their importance in the field, ligand activation of TPCs and the molecular mechanisms underlying their ion selectivity are still poorly understood. Here, we set out to elucidate the mechanistic basis for the ion selectivity of human TPC2 (hTPC2) and the molecular mechanism of ligand-induced channel activation by the lipid PI(3,5)P2. We performed all-atom in silico electrophysiology simulations to study Na+and Ca2+permeation across hTPC2 in real-time and to investigate the conformational changes induced by the presence or absence of bound PI(3,5)P2. Our findings reveal that hTPC2 adopts distinct structures depending on the presence of PI(3,5)P2and elucidate the conformational transition pathways between these structures. Additionally, we examined the permeation mechanism, solvation states, and binding sites of ions during ion permeation through the pore. Our simulations reproduce the experimental observation that hTPC2 is more selective for Na+over Ca2+ions in the presence of PI(3,5)P2and explain the mechanism of this ion selectivity. They highlight the importance of specific ion binding sites at the luminal channel entrance, the selectivity filter, and the central channel cavity for ion conduction, enabling a distant knock-on mechanism for efficient permeation of Na+ions.
A whole-body micro-CT scan library that captures the skeletal diversity of Lake Malawi cichlid fishes
Authors: Bucklow Callum V. , Genner Martin J. , Turner George F. , Maclaine James , Benson Roger , Verd Berta
Published: November 2023

Here we describe a dataset of freely available, readily processed, whole-bodyμCT-scans of 56 species (116 specimens) of Lake Malawi cichlid fishes that captures a considerable majority of the morphological variation present in this remarkable adaptive radiation. We contextualise the scanned specimens within a discussion of their respective ecomorphological groupings and suggest possible macroevolutionary studies that could be conducted with these data. We also describe a methodology to efficientlyμCT-scan (on average) 23 specimens per hour, limiting scanning time and alleviating the financial cost whilst maintaining high resolution. We demonstrate the utility of this method by reconstructing 3D models of multiple bones from multiple specimens within the dataset. We hope this dataset will enable further morphological study of this fascinating system and permit wider-scale comparisons with other cichlid adaptive radiations.
Diversity of arbuscular mycorrhizal fungi under the rhizosphere soil of different cropping systems surrounding Hawassa town, South Ethiopia
Authors: Zeleke Girma , Dobo Beyene , Asefa Fassil
Published: November 2023

This research was conducted to study the diversity of Arbuscular Mycorrhizal Fungi (AMF) in the rhizosphere of different plants at the vicinity of Hawassa city, Southern Ethiopia. The rate of root colonisation and diversity of AMF in the rhizosphere soils of permanent crops, major annual crops, forest areas, and open grazing fields were investigated. It discovered 928 spores of 23 distinct AMF morpho-species in 12 AMF genera and 12 annual and perennial crops. The AMF genera identified were: Acaulospora, Cetraspora, Claroideoglomus, Dentiscutata, Diversispora, Funneliformis, Gigaspora, Glomus, Racocetra, Rhizophagus, Sclerocystis, and Scutellospora. In tomatoes grown inorganically, a compromised species richness may result from the extensive use of agrochemicals. Further research into the effects of agricultural inputs on the subsurface microbial population may be necessary, as this is outside the purview of this publication. When compared to all other land uses, the AMF beneath the rhizosphere soil of Eucalyptus trees has the largest biomass, with spore density of 1907.4±0.404 spores 100g-1 of dry soil. The lowest AMF biomass has been recorded in the rhizosphere soil of Mango tree, with spore density of 260.1±0.121 spores 100g-1dry soil. The results of this study show that the mycorrhizal colonisation and spore density of the plants under investigation are decreased by monocropping, intense agricultural practises, and the application of inorganic fertilisers. Thus, it is thought that conservation agriculture, together with the development of plant species consortiums in agricultural polts, will preserve the biological diversity of Arbuscular mycorrhizal fungi and the integrity of the environment.

Significance of the study to the field

- plant species diversity is dependent on arbuscular mycorrhizal fungi diversity and density

- AMF Favours environmental resilience, carbon sequestration, and improves soil structure

- Application of inorganic agricultural inputs decrease, AMF diversity

- AMF diversity is affected by land use change, environmental pollution and climate change
Fine-tuning of Fgf8 morphogen gradient by heparan sulfate proteoglycans in the extracellular matrix
Authors: Gupta Mansi , Kurth Thomas , Heinemann Fabian , Schwille Petra , Keil Sebastian , Knopf Franziska , Brand Michael
Published: November 2023

Embryonic development is orchestrated by the action of morphogens, which spread out from a local source and activate, in a field of target cells, different cellular programs based on their concentration gradient. Fibroblast growth factor 8 (Fgf8) is a morphogen with important functions in embryonic organizing centers. It forms a gradient in the extracellular space by free diffusion, interaction with the extracellular matrix (ECM) and receptor-mediated endocytosis. However, morphogen gradient regulation by ECM is still poorly understood. Here we show that specific Heparan Sulfate Proteoglycans (HSPGs) bind Fgf8 directly in the ECM of living zebrafish embryos, thus affecting its diffusion and signaling. Using single-molecule Fluorescence Correlation Spectroscopy, we quantify this bindingin vivo, and find two different modes of interaction. First, reducing or increasing the concentration of specific HSPGs in the extracellular space alters Fgf8 diffusion, and thus, its gradient shape. Second, ternary complex formation of Fgf8 ligand with Fgf-receptors and HSPGs at the cell surface requires HSPG attachment to the cell membrane. Together, our results show that graded Fgf8 morphogen distribution is achieved by constraining free Fgf8 diffusion through successive interactions with HSPGs at the cell surface and in ECM space.

Statement of significance

Fgf8 is a secreted morphogen signaling molecule that instrúcts neighboring arrays of undifferentiated cells about their position and cellular identity in tissue. Fgf8 and other morphogens are often distributed in a graded fashion, and can typically work at very low concentrations. To reproducibly generate information in developing tissue, mechanisms have evolved to carefully control distribution and concentration of Fgf8 morphogen. We show that freely diffusing Fgf8 morphogen moves through interstitial cell spaces on its way to target cells, and while doing so, interacts with ECM molecules in these spaces and at cell surfaces via low affinity, reversible binding. These interactions are important tuning mechanisms that contribute to forming the Fgf8 morphogen gradient and to cell surface receptor binding, and thus, to controlling cell type identity.

Abstract Figure

Graphical abstract

To generate a gradient, the morphogen Fgf8 shuttles between fast free diffusion through extracellular space (i), slow diffusion or immobility (ii, iii) when bound to Heparan Sulfate Proteoglycans (HSPGs), in the extracellular matrix (ECM) and at cell surface receptors (iv), as revealed by single molecule studies in living zebrafish embryos.
Managing risks in IPD-ish projects: experience from Hong Kong
Authors: Ma Qiuwen , Cheung Sai On , Li Shan
Published: November 2023

Purpose

Integrated project delivery (IPD) project that does not use multiparty agreement is identified as IPD-ish. The use of IPD-ish arrangement by incorporating integration practices in conventional contract can be viewed as the part of the adoption process of IPD. Moreover, inappropriate integration practices invite new forms of risks and the absence of multiparty agreement adds to the challenges of risk management in IPD-ish projects. This study discusses such challenges and proposes the use of joint risk management to address the potential pitfalls in IPD-ish arrangement.

Design/methodology/approach

A mixed research method was applied. First, the criticality of IPD-ish general and integration-specific risks was examined through a survey. Second, a real IPD-ish project was used to exemplify the use of joint risk management (JRM) to manage IPD-ish risks.

Findings

Two types of risks, namely integration risks (IRs) and general risks (GRs), are identified in IPD-ish projects. Two major findings for the IRs: (1) the most critical IRs are related to unbalanced incentivization and inefficient multidisciplinary teams; and (2) only team formation related pre-contract JRM strategies affect IRs. As for the GRs, the most critical ones are associated with design issues and can be effectively mitigated by post-contract JRM.

Originality/value

Using IPD-ish arrangement is an inevitable part of implementation of full IPD. This happens as many change-averse owners would like to test the integration principles using a conventional contract that they are familiar with. In fact, success in IPD-ish would pave the path for further adoption of IPD. This study offers insight into categorization of risks in IPD-ish projects. Appropriate use of post-contract and organization related pre-contract JRM would improve the chance of teasing out the values of IPD through IPD-ish arrangements. Care should be taken to introduce some contracting integration initiatives, such as risk/reward sharing incentive.
Perceptions of Airbnb’s impact beyond the tourist bubbles of Cusco, Peru: an exploration of resident irritability
Authors: Arevalo Mildred , Day Jonathon , Sotomayor Sandra , Guillen Nancy Karen
Published: November 2023

Purpose

Specifically, this study aims to examine residents’ perceptions regarding the following: the sociocultural, environmental and economic impacts generated by the presence of Airbnb and the irritability caused by the presence of Airbnb based on Doxey’s Doxey (1975) irritation index (i.e. index).

Design/methodology/approach

Twenty-one semistructured in-depth interviews were conducted between February and March 2021 with residents of three condominiums in the Huancaro residential complex. Data were analyzed using the qualitative data analysis software ATLAS.ti 8.

Findings

Results showed that participants perceived negative economic impacts regarding investments, jobs, real estate prices and overall cost of living; negative sociocultural impacts regarding criminality, social conflicts and cultural exchange; and negative environmental impacts regarding sanitation in the context of the pandemic and the state of the Airbnb apartments. Further, it was found that participants related to the following three of the four stages of irritability: euphoria, apathy and annoyance.

Research limitations/implications

It is necessary to complement the information with the perceptions of the residents about the city’s authorities and managers in the hotel business before the stage of the COVID-19 pandemic and the current stage.

Practical implications

The study identifies improve Airbnb operations like establishing health paraments and defining cohabitation rules at the condominiums.

Social implications

The residents consider that visitors’ returns produce positive and negative impacts on the quality of life being important for understanding their perceptions.

Originality/value

Short-term rental companies, such as Airbnb, generate a range of impacts on urban residents, particularly when travelers encroach on areas of the city beyond the traditional “tourist bubbles.” This study explored the perceptions of Airbnb’s impacts on activities among residents of Huancaro, a residential section of Cusco-Peru, in the context of tourism reopening after a year of an almost complete halt in tourism activities because of the COVID-19 pandemic. The study also highlighted the heterogenetic responses to Airbnb within the community.
Mataram mosques management: intention to place mosque funds in Islamic banks
Authors: Adriansyah Lalu Rizky , As-Salafiyah Aisyah
Published: November 2023

Purpose

This study aims to examine idle funds in mosques in Mataram City and analyze the intentions of the mosque chairman to place mosque funds in Sharia banks. Six variables are used to analyze the intention; attitudes, subjective norms, behavioral control, sharia financial literacy, sharia banking knowledge and the responsibility of the management for the trust of the society.

Design/methodology/approach

This research consists of two studies; descriptive research examining idle funds of mosques and correlational research analyzing the intentions of mosque directors to place mosque funds in Sharia banks. Intentions will be analyzed using the theory of planned behavior approach, developed through the PLS-SEM method, and the data obtained from questionnaires through surveys were processed using the SmartPLS 3 application.

Findings

This study found that the average surplus between income and expenditure reaches IDR2.7m monthly. Also, 75% of mosques have placed their funds in Islamic banks. This study shows a positive relationship between the level of Islamic financial literacy, knowledge of Islamic banking, responsibility for public trust, attitudes toward Islamic banking, subjective norms and behavioral control in influencing the intentions to place mosque funds in Islamic banks. However, only behavioral control is accepted as it significantly influences intentions. Behavioral control means that to maximize intentions, Islamic banks need to make it easier for mosque administrators to place funds.

Originality/value

This research signifies a pioneering effort in examining idle funds within mosques, particularly those equipped with comprehensive financial reports within Mataram City. Furthermore, it spearheads an inquiry into the intentions of mosques to channel their funds into Sharia banks, underpinned by rigorous quantitative methodologies.
A spatio-temporal framework to assess urban heat island effect on Yeni Mamak urban transformation zone (Ankara, Türkiye)
Authors: Baş Bütüner Funda , Cakmakli Aysem Berrin , Karakadilar Ahmet Can , Deniz Esra
Published: November 2023

Purpose

This article explores the impacts of the changing land-use on urban heat island (UHI) in an urban transformation zone in Ankara (Türkiye). Identifying a characteristic rural landscape until the 1950s, the study area experienced a drastic land-use change by razing the fertile landscape of the city and replacing it with a sealed surface. Development of the squatter houses after the 1960s and, subsequently, the implementation of a new housing morphology have introduced new sceneries, scales and surface conditions that make the study area a noteworthy case to analyze.

Design/methodology/approach

Regarding the drastic spatio-temporal change of the study area, this research assesses the impacts of the changing land-use on UHI based on three periods. Using 1957, 1991 and 2021 aerial imaginaries and maps, it analyzes the temperature alteration caused by the changing land-use. To do so, different surface types, green patterns and built-up areas have been modeled using Ankara climatic data and transferred to ENVI-Met to calculate the Universal Thermal Climate Index (UTCI) values.

Findings

The calculation has been developed over a transect covering an area of 40 m × 170 m, which includes diversity in terms of architecture, landscape and open space elements. To encourage future design strategies, the research findings deliberate into three extents that discuss the lacking climate knowledge in the ongoing urban transformation projects: impervious surface ratio and regional albedo variation, changing aspect ratio and temperature variation at the pedestrian level.

Originality/value

Urban transformation projects, being countrywide operations in Türkiye, need to cover climate-informed design strategies. Herein, the article underlines the critical position of design decisions in forming a climate-informed urban environment. Dwelling on a typical model of housing transformation in Türkiye, the research could trigger climate-informed urban development strategies in the country.
Related party transactions, accrual-based earnings management and real activities earnings management in emerging market
Authors: Khuong Nguyen Vinh , Liem Nguyen Thanh , Anh Le Huu Tuan , Dung Bui Thi Ngan
Published: November 2023

Purpose

The purpose of this study is to examine the association between related party transactions (RPTs) in terms of sales and purchases and earnings management (EM).

Design/methodology/approach

The authors use the estimation method of system generalized method of moments (Sys-GMM) on a sample of 413 non-financial firms in Vietnam in the period from 2015 to 2019, totaling 1,638 firm-year observations. Multiple proxies for RPTs and EM are used to provide a comprehensive assessment of the relationship between the two factors.

Findings

There is a positive association between RPTs and EM, suggesting that both types of RPTs could reduce financial reporting quality and allow firms to be more engaged in earnings manipulation.

Originality/value

There are a number of studies investigating the above link, but they tend to use aggregate values (the sum of both sales and purchases with related parties) or just either accruals-based earnings or real EM. This study is the first to extend the literature on the relationship between RPTs and EM by examining both sales-based and purchases-based RPTs on both real and accruals-based earnings manipulation. This approach helps uncover the differences in the effect of the two types of RPTs on both types of upward EM.
A systematic review of diabetic retinopathy screening intervals
Authors: Drinkwater Jocelyn J. , Kalantary Amy , Turner Angus W.
Published: November 2023

The current evidence on whether annual diabetic retinopathy (DR) screening intervals can be extended was reviewed. A systematic review protocol was followed (PROSPERO ID: CRD42022359590). Original longitudinal articles that specifically assessed DR screening intervals were in English and collected data after 2000 were included. Two reviewers independently conducted the search and reviewed the articles for quality and relevant information. The heterogeneity of the data meant that a meta‐analysis was not appropriate. Twelve publications were included. Studies were of good quality and many used data from DR screening programs. Studies fit into three categories; those that assessed specific DR screening intervals, those that determined optimal DR screening intervals and those that developed/assessed DR screening risk equations. For those with type 2 diabetes, extending screening intervals to 3‐ to 4‐yearly in those with no baseline DR appeared safe. DR risk equations considered clinical factors and allocated those at lower risk of DR progression screening intervals of up to five years. Those with baseline DR or type 1 diabetes appeared to have a higher risk of progression to STDR and needed more frequent screening. DR screening intervals can be extended to 3–5 yearly in certain circumstances. These include patients with type 2 diabetes and no current DR, and those who have optimal management of other risk factors such as glucose and blood pressure.
Treasures & Baggage: A New Way to Navigate Change
Authors: Sadhujan Sruthi
Published: November 2023

All around us, from large corporations to universities, from design consultancies to small businesses, we are all, as individuals and organizations, facing a massive cultural upheaval.

It's no surprise that we're living in the midst of incredible change. As tempting as it is to race to embrace the new, maybe a closer examination of what to keep and what to get rid of will ultimately lead to real, more productive change.
The demand for extraterritoriality: Religious minorities in nineteenth‐century Egypt
Authors: Artunç Cihan , Saleh Mohamed
Published: November 2023

The transplantation of European legal systems in the periphery often occurred via semi‐colonial institutions, where Europeans were subject to their own jurisdictions that placed them outside the reach of local courts. In nineteenth‐century Egypt, the option of extraterritoriality was extended to local non‐Muslims. Drawing on Egypt's population censuses in 1848 and 1868, we show that locals did not seek extraterritoriality to place themselves under more efficient jurisdictions. Rather, legal protection mitigated uncertainty about which law would apply to any contractual relationship in an environment where multiple legal systems co‐existed and overlapped.
Staged treatment response in status epilepticus: Lessons from the SENSE registry
Authors: Beuchat Isabelle , Novy Jan , Rosenow Felix , Kellinghaus Christoph , Rüegg Stephan , Tilz Christian , Trinka Eugen , Unterberger Iris , Uzelac Zeljko , Strzelczyk Adam , Rossetti Andrea O.
Published: November 2023

Objectives

Although in epilepsy patients the likelihood of becoming seizure‐free decreases substantially with each unsuccessful treatment, to our knowledge this has been poorly investigated in status epilepticus (SE). We aimed to evaluate the proportion of SE cessation and functional outcome after successive treatment steps.

Methods

We conducted a post hoc analysis of a prospective, observational, multicenter cohort (Sustained Effort Network for treatment of Status Epilepticus [SENSE]), in which 1049 incident adult SE episodes were prospectively recorded at nine European centers. We analyzed 996 SE episodes without coma induction before the third treatment step. Rates of SE cessation, mortality (in ongoing SE or after SE control), and favorable functional outcome (assessed with modified Rankin scale) were evaluated after each step.

Results

SE was treated successfully in 838 patients (84.1%), 147 (14.8%) had a fatal outcome (36% of them died while still in SE), and 11 patients were transferred to palliative care while still in SE. Patients were treated with a median of three treatment steps (range 1–13), with 540 (54.2%) receiving more than two steps (refractory SE [RSE]) and 95 (9.5%) more than five steps. SE was controlled after the first two steps in 45%, with an additional 21% treated after the third, and 14% after the fourth step. Likelihood of SE cessation (p < 0.001), survival (p = 0.003), and reaching good functional outcome (p < 0.001) decreased significantly between the first two treatment lines and the third, especially in patients not experiencing generalized convulsive SE, but remained relatively stable afterwards.

Significance

The significant worsening of SE prognosis after the second step clinically supports the concept of RSE. However, and differing from findings in human epilepsy, RSE remains treatable in about one third of patients, even after several failed treatment steps. Clinical judgment remains essential to determine the aggressiveness and duration of SE treatment, and to avoid premature treatment cessation in patients with SE.