bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioorthogonal labeling enables in situ fluorescence imaging of expressed gas vesicle nanostructures
Authors: Schrunk Erik , Dutka Przemysław , Hurt Robert C. , Wu Di , Shapiro Mikhail G.
Published: December 2023

Gas vesicles (GVs) are proteinaceous nanostructures that, along with virus-like particles, encapsulins, nano-cages, and other macromolecular assemblies are being developed for potential biomedical applications. To facilitate such development, it would be valuable to characterize these nanostructures’ sub-cellular assembly and localization. However, traditional fluorescent protein fusions are not tolerated by GVs’ primary constituent protein, making optical microscopy a challenge. Here, we introduce a method for fluorescently visualizing intracellular GVs using the bioorthogonal label FlAsH, which becomes fluorescent upon binding the six-amino acid tetracysteine (TC) tag. We engineered the GV subunit protein, GvpA, to display the TC tag, and showed that GVs bearing TC-tagged GvpA can be successfully assembled and fluorescently visualized in HEK 293T cells. We used fluorescence images of the tagged GVs to study GV size and distance distributions within these cells. This bioorthogonal labeling approach will enable research to provide a greater understanding of GVs and could be adapted to similar proteinaceous nanostructures.
Evidence of survival bias in the association betweenAPOE-Є4and age of ischemic stroke onset
Authors: von Berg Joanna , McArdle Patrick F. , Häppölä Paavo , Haessler Jeffrey , Kooperberg Charles , Lemmens Robin , Pezzini Alessandro , Thijs Vincent , Pulit Sara L. , Kittner Steven J. , Mitchell Braxton D. , de Ridder Jeroen , van der Laan Sander W.
Published: December 2023

Large genome-wide association studies (GWAS) employing case-control study designs have now identified tens of loci associated with ischemic stroke (IS). As a complement to these studies, we performed GWAS in a case-only design to identify loci influencing age at onset (AAO) of ischemic stroke. Analyses were conducted in a Discovery cohort of 10,857 ischemic stroke cases using a linear regression framework. We meta-analyzed all SNPs with p-value < 1×10−5in a sex-combined or sex-stratified analysis using summary data from two additional replication cohorts. In the women-only meta-analysis, we detected significant evidence for association of AAO with rs429358, an exonic variant inAPOEthat encodes for the APOE-є4 allele. Each copy of the rs429358:T>C allele was associated with a 1.29 years earlier stroke AOO (meta p-value = 2.48×10−11).

ThisAPOEvariant has previously been associated with increased mortality and ischemic stroke AAO. We hypothesized that the association with AAO may reflect a survival bias attributable to an age-related decline in mortality among APOE-є4 carriers and have no association to stroke AAO per se. Using a simulation study, we found that a variant associated with overall mortality might indeed be detected with an AAO analysis. A variant with a two-fold increase on mortality risk would lead to an observed effect of AAO that is comparable to what we found. In conclusion, we detected a robust association of theAPOElocus with stroke AAO and provided simulations to suggest that this association may be unrelated to ischemic stroke per se but related to a general survival bias.
Long-read RNA-seq atlas of novel microglia isoforms elucidates disease-associated genetic regulation of splicing
Authors: Humphrey Jack , Brophy Erica , Kosoy Roman , Zeng Biao , Coccia Elena , Mattei Daniele , Ravi Ashvin , Efthymiou Anastasia G. , Navarro Elisa , Muller Benjamin Z. , Snijders Gijsje JLJ , Allan Amanda , Münch Alexandra , Kitata Reta Birhanu , Kleopoulos Steven P , Argyriou Stathis , Shao Zhiping , Francoeur Nancy , Tsai Chia-Feng , Gritsenko Marina A , Monroe Matthew E , Paurus Vanessa L , Weitz Karl K , Shi Tujin , Sebra Robert , Liu Tao , de Witte Lot D. , Goate Alison M. , Bennett David A. , Haroutunian Vahram , Hoffman Gabriel E. , Fullard John F. , Roussos Panos , Raj Towfique
Published: December 2023

Microglia, the innate immune cells of the central nervous system, have been genetically implicated in multiple neurodegenerative diseases. We previously mapped the genetic regulation of gene expression and mRNA splicing in human microglia, identifying several loci where common genetic variants in microglia-specific regulatory elements explain disease risk loci identified by GWAS. However, identifying genetic effects on splicing has been challenging due to the use of short sequencing reads to identify causal isoforms. Here we present the isoform-centric microglia genomic atlas (isoMiGA) which leverages the power of long-read RNA-seq to identify 35,879 novel microglia isoforms. We show that the novel microglia isoforms are involved in stimulation response and brain region specificity. We then quantified the expression of both known and novel isoforms in a multi-ethnic meta-analysis of 555 human microglia short-read RNA-seq samples from 391 donors, the largest to date, and found associations with genetic risk loci in Alzheimer’s disease and Parkinson’s disease. We nominate several loci that may act through complex changes in isoform and splice site usage.
Comparative studies of genetic and phenotypic associations for 2,168 plasma proteins measured by two affinity-based platforms in 4,000 Chinese adults
Authors: Wang Baihan , Pozarickij Alfred , Mazidi Mohsen , Wright Neil , Yao Pang , Said Saredo , Iona Andri , Kartsonaki Christiana , Fry Hannah , Lin Kuang , Chen Yiping , Du Huaidong , Avery Daniel , Schmidt Dan Valle , Yu Canqing , Sun Dianjianyi , Lv Jun , Hill Michael , Li Liming , Bennett Derrick A , Collins Rory , Walters Robin G , Clarke Robert , Millwood Iona Y , Chen Zhengming
Published: December 2023

Proteomics offers unique insights into human biology and drug development, but few studies have directly compared the utility of different proteomics platforms. We measured 2,168 plasma proteins in 3,976 Chinese adults using both OLINK and SomaScan platforms and compared their genetic determinants and associations with traits and disease risk. For 1,694 proteins with one-to-one matched reagents, there was a modest between platform correlation (median rho=0.20). OLINK-proteins had fewertrans-pQTLs (766 vs 812 proteins) but morecis-pQTLs (725 vs 565) than SomaScan-proteins, including 342 with colocalisingcis-pQTLs. Moreover, 1,095 OLINK- and 963 SomaScan-proteins showed significant associations with BMI, while 279 and 165 proteins were significantly associated with IHD, respectively. Addition of these IHD-associated proteins to conventional risk factors yielded NRIs for IHD of 15.3% and 17.1% for OLINK and SomaScan respectively. The results demonstrate the complementarity of different proteomic platforms and should inform assay selection in future population and clinical studies.
The virtual multiple sclerosis patient: on the clinical-radiological paradox
Authors: Sorrentino P , Pathak A , Ziaeemehr A , Troisi Lopez E , Cipriano L , Romano A , Sparaco M , Quarantelli M , Banerjee A , Sorrentino G , Hashemi M , Jirsa V
Published: December 2023

Multiple sclerosis (MS) is typically diagnosed based on the clinical presentation, the presence of structural MRI lesions, and a “no better explanation” criterion. The structural lesions, disseminated in time and space, are a consequence of autoimmune processes leading to the damage of the myelin sheath in the central nervous system. As such, one would expect that more lesions would relate to higher clinical disability. However, a conflicting scenario is often present, with a high lesion load related to mild clinical impairment, and vice versa, a phenomenon referred to as the “clinico-radiological paradox”. The myelin damage in MS is widespread, which is likely mirrored in a widespread slowing of conduction velocities. However, conduction velocities are typically measured on selected white-matter tracts (e.g., visual evoked potentials), which do not directly relate to clinical impairment. In this paper, we hypothesize that the overall slowing of conduction velocities (i.e., across all brain tracts) is a better predictor of clinical disability. However, estimating the whole-brain average velocities is challenging. To overcome this obstacle, we estimated patient-specific conduction velocities in MS patients by merging multimodal data (i.e., DTI and source-reconstructed magnetoencephalography) to inform large-scale brain models, fitted on each individual patient. We started from the known reduction of the power of the alpha frequency band, as well as the shift in its peak, observed in MS patients. We then reproduced these individual spectral features in silico using large-scale models based on the individual connectomes. We then used state-of-the-art deep neural networks for Bayesian model inversion to estimate the most likely average conduction velocity in each patient, given the observed spectral features (and the connectomes). Finally, we used the inferred conduction velocities to predict the individual clinical disability. We find that the conduction velocities inferred for patients are significantly lower than those inferred for controls and that they are predictive of individual clinical disability, well above the predictive power of demographic and clinical variables and lesion load. Our results suggest a biologically and physically plausible solution to the “clinico-radiological” paradox, where the inferred, individual changes in conduction velocities across the whole networks are proposed as causative to the clinical disability.
Three-dimensional Isotropic Imaging of Live Suspension Cells Enabled by Droplet Microvortices
Authors: Cardenas-Benitez Braulio , Hurtado Richard , Luo Xuhao , Lee Abraham P.
Published: December 2023

Three-dimensional (3D) imaging of non-adherent cells in suspension media is challenging due to their propensity to drift when not fixed to a substrate, as required by optical sectioning technologies. Resolution differences in the lateral versus depth directions typically present in those systems further complicates single-cell morphometry of cellular features indicative of effector functions, such as cytosol and organelle volumetric distribution, and cell membrane topography. Here, we present a method for 3D fluorescent isotropic imaging of live, non-adherent single cells encapsulated in picoliter droplets using Optical Projection Tomography (OPT) enabled by droplet microvortices. Our microfluidic platform features a droplet trap array that leverages flow-induced droplet interfacial shear to generate intra-droplet microvortices, which in turn are modulated to rotate single-cells on their axis to enable OPT-based imaging. This strategy allows observation of cells encapsulated inside non-toxic isotonic buffer droplets and facilitates scalable OPT acquisition by the simultaneous spinning of hundreds of cells. Specifically, we demonstrate 3D imaging of live myeloid and lymphoid cells in suspension, including K562 cells, as well as naïve and activated T cells—small cells prone to movement in their suspended phenotype. In addition, morphometry of primary T cells under different immunological activation states allowed us to identify six distinct nuclear content distributions, which differ from the conventional 2D images depicting spheroid and bean-like nuclear shapes commonly associated with lymphocytes. This Arrayed-Droplet Optical Projection Tomography (ADOPT) technology is capable of isotropic, single live-cell 3D imaging and has the potential to perform large-scale morphometry of immune cell effector function states, while providing compatibility with microfluidic droplet operations.
Mechanism of homology search expansion during recombinational DNA break repair
Authors: Dumont Agnès , Mendiboure Nicolas , Savocco Jérôme , Anani Loqmen , Moreau Pierrick , Thierry Agnès , Modolo Laurent , Jost Daniel , Piazza Aurèle
Published: December 2023

Homology search catalyzed by a RecA/Rad51 nucleoprotein filament (NPF) is a central step of DNA double-strand break (DSB) repair by homologous recombination. How it operates in cells remains elusive. Here we developed a Hi-C-based methodology to map single-stranded DNA (ssDNA) contacts genome-wide inS. cerevisiae, which revealed two main homology search phases. Initial search conducted by short NPFs is confined incisby cohesin-mediated chromatin loop folding. Progressive growth of stiff NPFs enables exploration of distant genomic sites. Long-range resection by Exo1 drives this transition from local to genome-wide search by providing ssDNA substrates for assembly of extensive NPFs. DSB end-tethering promotes coordinated homology search by NPFs formed on the two DSB ends. Finally, an autonomous genetic element on chromosome III engages the NPF and stimulates homology search in its vicinity. This work reveals the mechanism of the progressive and uneven expansion of homology search orchestrated by chromatin organizers, long-range resection, end-tethering, specialized genetic elements, and that exploits the stiff NPF structure conferred by Rad51 oligomerization.

Highlights

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Cohesin-mediated chromatin loops constrain homology search incisfor NPF regions close to the resection front

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Stiffening of ssDNA by Rad51 enables genome-wide homology search by DSB-proximal sites

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Exo1-mediated long-range resection promotes genome-wide homology search

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DSB end-tethering promotes coordinated homology search by NPFs formed on both DSB ends

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The recombination enhancer focuses homology search in its vicinity
A point cloud segmentation framework for image-based spatial transcriptomics
Authors: Defard Thomas , Laporte Hugo , Ayan Mallick , Juliette Soulier , Curras-Alonso Sandra , Weber Christian , Massip Florian , Londoño-Vallejo José-Arturo , Fouillade Charles , Mueller Florian , Walter Thomas
Published: December 2023

Recent progress in image-based spatial RNA profiling enables to spatially resolve tens to hundreds of distinct RNA species with high spatial resolution. It hence presents new avenues for comprehending tissue organization. In this context, the ability to assign detected RNA transcripts to individual cells is crucial for downstream analyses, such as in-situ cell type calling. Yet, accurate cell segmentation can be challenging in tissue data, in particular in the absence of a high-quality membrane marker. To address this issue, we introduce ComSeg, a segmentation algorithm that operates directly on single RNA positions and that does not come with implicit or explicit priors on cell shape. ComSeg is thus applicable in complex tissues with arbitrary cell shapes. Through comprehensive evaluations on simulated datasets, we show that ComSeg outperforms existing state-of-the-art methods for in-situ single-cell RNA profiling and cell type calling. On experimental data, our method also demonstrates proficiency in estimating RNA profiles that align with established scRNA-seq datasets. Importantly, ComSeg exhibits a particular efficiency in handling complex tissue, positioning it as a valuable tool for the community.
First detection ofAnopheles stephensiin Ghana using molecular surveillance
Authors: Afrane Yaw A. , Abdulai Anisa , Mohammed Abdul R. , Akuamoah-Boateng Yaw , Owusu-Asenso Christopher Mfum , Sraku Isaac K. , Yanney Stephina A. , Malm Keziah , Lobo Neil F.
Published: December 2023

The invasiveAnopheles stephensimosquito has been rapidly expanding in range in Africa over the last decade, spreading from the Indian sub-continent to several East African countries (Djibouti, Ethiopia, Sudan, Somalia and Kenya) and now in West Africa, Nigeria. The rapid expansion of this invasive vector poses a major threat to current malaria control and elimination efforts. In line with the WHO’s strategy to stop the spread of this invasive species by enhancing surveillance and control measures in Africa, we incorporated morphological and molecular surveillance ofAn. stephensiinto routine entomological surveillance of malaria vectors in the city of Accra, Ghana. Here, we report on the first detection ofAn. stephensiin Ghana.An. stephensimosquitoes were confirmed using PCR and sequencing of the ITS2 regions. These findings highlight the urgent need for increased surveillance and response strategies to mitigate the spread ofAn. stephensiin Ghana.
Cryo-EM structures of human α1B/βI+βIVb microtubules shed light on isoform specific assembly
Authors: Zehr Elena A. , Roll-Mecak Antonina
Published: December 2023

Microtubules are dynamic polymers assembled from αβ-tubulin dimers. Mammals have multiple α and β-tubulin isoforms. Despite a high degree of conservation, microtubules assembled from different tubulin isoforms have unique dynamic properties. How isoform sequence variation affects polymerization interfaces and nucleotide dependent conformational changes in microtubules is still not well understood. Here we report 2.9Å resolution cryo-EM structures of human α1B/βI+βIVb microtubules in the GDP state, and a GTP-like state, bound to GMPCPP. Our structures show that, similar to microtubules assembled from other mammalian isoforms, transition from the GTP to the GDP states in α1B/βI+βIVb microtubules results in strengthening of the longitudinal interface and an overall compaction of the axial dimer repeat distance in the lattice. Interestingly, we find that α-tail residues link longitudinally adjacent tubulin dimers through interactions with two conserved arginine residues in β-tubulin that are mutated in human disease. Comparative analysis of tubulin isoforms shows minimal isoform-specific effects at the longitudinal interface or the α-tubulin lateral interface, but a high concentration of sequence variability in the second shell of residues away from the β-tubulin lateral interface which can modulate polymerization interfaces and thus impact microtubule dynamics.
Leptomeningeal Neural Organoid (LMNO) Fusions as Models to Study Meninges-Brain Signaling
Authors: Jones Hannah E , Robertson Gabriella L , Romero-Morales Alejandra , O’Rourke Rebecca , Siegenthaler Julie A , Gama Vivian
Published: December 2023

Neural organoids derived from human induced pluripotent stem cells (iPSCs) provide a model to study the earliest stages of human brain development, including neurogenesis, neural differentiation, and synaptogenesis. However, neural organoids lack supportive tissues and some non-neural cell types that are key regulators of brain development. Neural organoids have instead been co-cultured with non-neural structures and cell types to promote their maturation and model interactions with neuronal cells. One structure that does not formde novowith neural organoids is the meninges, a tri-layered structure that surrounds the CNS and secretes key signaling molecules required for mammalian brain development. Most studies of meninges-brain signaling have been performed in mice or using two-dimensional (2D) cultures of human cells, the latter not recapitulating the architecture and cellular diversity of the tissue. To overcome this, we developed a co-culture system of neural organoids generated from human iPSCs fused with fetal leptomeninges from mice with fluorescently labeled meninges (Col1a1-GFP). These proof-of-concept studies test the stability of the different cell types in the leptomeninges (fibroblast and macrophage) and the fused brain organoid (progenitor and neuron), as well as the interface between the organoid and meningeal tissue. We test the longevity of the fusion pieces after 30 days and 60 days in culture, describe best practices for preparing the meninges sample prior to fusion, and examine the feasibility of single or multiple meninges pieces fused to a single organoid. We discuss potential uses of the current version of the LMNO fusion model and opportunities to improve the system.
PIEZO2‐dependent rapid pain system in humans and mice
Authors: Bouchatta Otmane , Brodzki Marek , Manouze Houria , Carballo Gabriela B. , Kindström Emma , de‐Faria Felipe M. , Yu Huasheng , Kao Anika R. , Thorell Oumie , Liljencrantz Jaquette , Ng Kevin K. W. , Frangos Eleni , Ragnemalm Bengt , Saade Dimah , Bharucha‐Goebel Diana , Szczot Ilona , Moore Warren , Terejko Katarzyna , Cole Jonathan , Bonnemann Carsten , Luo Wenquin , Mahns David A. , Larsson Max , Gerling Gregory J. , Marshall Andrew G. , Chesler Alexander T. , Olausson Håkan , Nagi Saad S. , Szczot Marcin
Published: December 2023

The PIEZO2 ion channel is critical for transducing light touch into neural signals but is not considered necessary for transducing acute pain in humans. Here, we discovered an exception – a form of mechanical pain evoked by hair pulling. Based on observations in a rare group of individuals with PIEZO2 deficiency syndrome, we demonstrated that hair-pull pain is dependent on PIEZO2 transduction. Studies in control participants showed that hair-pull pain triggered a distinct nocifensive response, including a nociceptive reflex. Observations in rare Aβ deafferented individuals and nerve conduction block studies in control participants revealed that hair-pull pain perception is dependent on Aβ input. Single-unit axonal recordings revealed that a class of cooling-responsive myelinated nociceptors in human skin is selectively tuned to painful hair-pull stimuli. Further, we pharmacologically mapped these nociceptors to a specific transcriptomic class. Finally, using functional imaging in mice, we demonstrated that in a homologous nociceptor, Piezo2 is necessary for high-sensitivity, robust activation by hair-pull stimuli. Together, we have demonstrated that hair-pulling evokes a distinct type of pain with conserved behavioral, neural, and molecular features across humans and mice.
Enhancing the auditor's mindset: a framework for nurturing professional skepticism
Authors: Kelly Martin , Larres Patricia
Published: December 2023

Purpose

Following recent high-profile audit failures, concern has been expressed that auditors are not demonstrating sufficient skepticism when exercising professional judgment. In particular, client assumptions and estimations relating to hypothetical valuations in financial reporting are not being challenged. This paper seeks to address the issue by advancing a decision-making framework aimed at guiding auditors beyond regulatory reductionist thinking towards an enhanced understanding of the cognitive processes which shape professional judgment in forming a reliable audit opinion.

Design/methodology/approach

Drawing on the normative philosophical and theological teachings of Bernard Lonergan, the authors' decision-making framework embodies reflective thinking and the data of consciousness to highlight the central role played by enquiry in the dynamics of understanding, judgment and decision-making. Such enquiry elicits challenge of the management bias inherent in hypothetical valuations.

Findings

Auditing through a Lonerganian lens allows auditors to reflect on their approach to objective decision-making by offering a set of cognitive tools to enhance the enquiry essential for nurturing professional skepticism.

Originality/value

This paper contributes to the literature by developing the somewhat neglected discourse on the cognitive processes essential for professional skepticism and audit judgment. The authors demonstrate how Lonerganian self-appropriation intensifies an awareness of the recursive cognitive activities pertinent to objective judgment and decision-making. This awakened consciousness has the potential not only to change how auditors question evidence to make informed judgments and decisions, but also to normalize the practice of challenge.
AI credibility and consumer-AI experiences: a conceptual framework
Authors: Khan Abdul Wahid , Mishra Abhishek
Published: December 2023

Purpose

This study aims to conceptualize the relationship of perceived artificial intelligence (AI) credibility with consumer-AI experiences. With the widespread deployment of AI in marketing and services, consumer-AI experiences are common and an emerging research area in marketing. Various factors affecting consumer-AI experiences have been studied, but one crucial factor – perceived AI credibility is relatively underexplored which the authors aim to envision and conceptualize.

Design/methodology/approach

This study employs a conceptual development approach to propose relationships among constructs, supported by 34 semi-structured consumer interviews.

Findings

This study defines AI credibility using source credibility theory (SCT). The conceptual framework of this study shows how perceived AI credibility positively affects four consumer-AI experiences: (1) data capture, (2) classification, (3) delegation, and (4) social interaction. Perceived justice is proposed to mediate this effect. Improved consumer-AI experiences can elicit favorable consumer outcomes toward AI-enabled offerings, such as the intention to share data, follow recommendations, delegate tasks, and interact more. Individual and contextual moderators limit the positive effect of perceived AI credibility on consumer-AI experiences.

Research limitations/implications

This study contributes to the emerging research on AI credibility and consumer-AI experiences that may improve consumer-AI experiences. This study offers a comprehensive model with consequences, mechanism, and moderators to guide future research.

Practical implications

The authors guide marketers with ways to improve the four consumer-AI experiences by enhancing consumers' perceived AI credibility.

Originality/value

This study uses SCT to define AI credibility and takes a justice theory perspective to develop the conceptual framework.
The limitations of open innovation: an examination of innovation orientation, open innovation and performance in North America
Authors: Wilson Grant Alexander , Case Tyler , Dobni C. Brooke , Liguori Eric
Published: December 2023

Purpose

Prior innovation orientation research has mostly focused on performance consequences, with some recent work examining its relationship with innovative practices such as open innovation. Yet, despite this growing body of open innovation research, there are still gaps and limitations. Notably, most prior studies have been conducted in Europe, limiting their generalizability to the rest of the world, and are replicative, exploring performance and competitive outcomes. There is very limited work examining the potential limitations of open innovation. This study extends innovation orientation research and examines the limitations of open innovation in North America.

Design/methodology/approach

This study explores the relationships between innovation orientation and performance, open innovation and performance and innovation orientation and open innovation among 386 North American companies.

Findings

This study is novel as it examines the relationships between innovation orientation and performance, open innovation and performance and innovation orientation and open innovation among North American companies. The research uncovers a linear relationship between innovation orientation and performance, a correlation between innovation orientation and open innovation and a counterintuitive curvilinear relationship between open innovation and performance. The curvilinear relationship, shaped as an inverted u-shape, suggests there are limitations to the strategy's effectiveness, actionable insight to companies, consultants and scholars alike. In the discussion section, findings are further unpacked with regard to their implications for the scholarly literature. The paper concludes with managerial considerations for creating an innovation orientation and the most effective level of open innovation for maximum competitive and performance implications.

Originality/value

Beyond the innovation orientation and open innovation research contributions, this study offers managerial insight for executives seeking to enhance competitiveness and drive firm performance.
Does geopolitical risk impact the natural resources—Economic growth nexus?
Authors: Hashmi Shabir Mohsin , Wan Muchun , Syed Qasim Raza
Published: December 2023

The existing literature on resource economics extensively probes the validity of the natural resource curse hypothesis; nevertheless, the empirical evidence at the global scale is relatively sparse. Further, the literature ignores the combined impact of geopolitical risk (GPR) and natural resources (NRR) on economic growth (EG). Based on this, we examine whether the natural resource curse hypothesis holds at the global level. Moreover, we investigate the combined impact of NRR and GPR on EG. We adopt the novel Fourier‐augmented ARDL method to provide reliable outcomes. The results delineate that NRR upsurge EG, thereby invalidating the resource curse hypothesis. Contrarily, the combined impact of NRR and GPR on EG is negative, thus, validating the resource curse hypothesis. We recommend a series of policy suggestions based on the outcomes.
Pathway to terrorist behaviors: The role of childhood experiences, personality traits, and ideological motivations in a sample of Iraqi prisoners
Authors: Cleary Sean D. , Candilis Philip J. , Dhumad Saleh , Dyer Allen R. , Khalifa Najat
Published: December 2023

Radicalization to terrorism is a multifaceted process with no single theory or approach to explain it. Although research has focused on understanding the process, there is still a dearth of studies that examine an empirically driven pathway to terrorism behavior. This study examines a cross‐sectional sample of incarcerated men convicted of terrorism in Iraq (N = 160). A questionnaire‐guided interview included adverse childhood experiences (ACEs), conduct disorder (CD), antisocial personality disorder (ASPD), religious and political ideology, views about causes of terrorism, and the severity of terrorist acts. Path analysis was employed to examine the relationships between these factors and to identify the model with the best fit. After adjusting for age, employment, and location, results indicated that ACEs positively impacted CD, ASPD, religious guidance, and terrorism attitudes. ASPD positively affected political commitment and terrorism attitudes, but inversely affected current religious commitment. Political commitment inversely influenced terrorism attitudes. Religious commitment positively influenced the prioritization of religion in life, which subsequently impacted terrorism attitudes and behavior severity. Additionally, attitudes toward terrorism directly affected the severity of terrorism behavior. All paths in the final model were statistically significant at p < 0.05. Although these findings may be limited in generalizability due to the unique sample, results support the complex and interdependent nature of childhood and adult experiences on the development of both terrorism attitudes and the severity of terrorism behavior.
Validation of image stream hashing: A forensic method for content verification
Authors: Wales Gregory S.
Published: December 2023

How do forensic examiners know if they have altered an image stream when converting a digital image from one codec or file container to another for analysis? Forensic standards and best practices recommend avoiding alteration or degradation of multimedia data during transcoding. An image stream hashing method was recently introduced to the forensic science community to answer the question above. This paper offers an initial validation study of image stream hashing method that may answer the question above. The first half of the study's experiments tested the image stream hashing method to measure fitness for use in forensic science while identifying errors and limitations. The study's second phase analyzed the systematic errors detected in initial tests to discover error causation. Causation analysis identified four method limitations subsequently used to develop proposed standard controls of method operations. The final study phase repeated the initial experiments used in the first phase while implementing the proposed standard controls of method operations. Initial test results indicated the method had significant error rates, limiting the effectiveness of the method to only three of the five file types used in the study. The final testing phase revealed that implementing proposed standard controls of method operations reduced the potential systematic errors to a negligible level when using the image stream hashing method for content verification. The validation study concluded that examiners could use the image stream hashing method for forensic science only by implementing error mitigation techniques that utilize the proposed standard controls of method operations.
Heterologous production of rhamnolipids in Pseudomonas chlororaphis subsp chlororaphis ATCC 9446 based on the endogenous production of N‐acyl‐homoserine lactones
Authors: González‐Valdez Abigail , Escalante Adelfo , Soberón‐Chávez Gloria
Published: December 2023

Rhamnolipids (RL) are biosurfactants naturally produced by the opportunistic pathogen Pseudomonas aeruginosa. Currently, RL are commercialized for various applications and produced by Pseudomonas putida due to the health risks associated with their large‐scale production by P. aeruginosa. In this work, we show that RL containing one or two rhamnose moieties (mono‐RL or di‐RL, respectively) can be produced by the innocuous soil‐bacterium Pseudomonas chlororaphis subsp chlororaphis ATCC 9446 at titres up to 66 mg/L (about 86% of the production of P. aeruginosa PAO1 in the same culture conditions). The production of RL depends on the expression of P. aeruginosa PAO1 genes encoding the enzymes RhlA, RhlB and RhlC. These genes were introduced in a plasmid, together with a transcriptional regulator (rhlR) forming part of the same operon, with and without RhlC. We show that the activation of rhlAB by RhlR depends on its interaction with P. chlororaphis endogenous acyl‐homoserine lactones, which are synthetized by either PhzI or CsaI autoinducer synthases (producing 3‐hydroxy‐hexanoyl homoserine lactone, 3OH‐C6‐HSL, or 3‐oxo‐hexanoyl homoserine lactone, 3O‐C6‐HSL, respectively). P. chlororaphis transcriptional regulator couple with 3OH‐C6‐HSL is the primary activator of gene expression for phenazine‐1‐carboxylic acid (PCA) and phenazine‐1‐carboxamide (PCN) production in this soil bacterium. We show that RhlR coupled with 3OH‐C6‐HSL or 3O‐C6‐HSL promotes RL production and increases the production of PCA in P. chlororaphis. However, PhzR/3OH‐C6‐HSL or CsaR/3O‐C6‐HSL cannot activate the expression of the rhlAB operon to produce mono‐RL. These results reveal a complex regulatory interaction between RhlR and P. chlororaphis quorum‐sensing signals and highlight the biotechnology potential of P. chlororaphis ATCC 9446 expressing P. aeruginosa rhlAB‐R or rhlAB‐R‐C for the industrial production of RL.
Dysbiosis of lower respiratory tract microbiome are associated with proinflammatory states in non‐small cell lung cancer patients
Authors: Li Yangqian , Rao Guanhua , Zhu Guonian , Cheng Cheng , Yuan Lijuan , Li Chengpin , Gao Jianpeng , Tang Jun , Wang Zhoufeng , Li Weimin
Published: December 2023

Background

The lung has a sophisticated microbiome, and respiratory illnesses are greatly influenced by the lung microbiota. Despite the fact that numerous studies have shown that lung cancer patients have a dysbiosis as compared to healthy people, more research is needed to explore the association between the microbiota dysbiosis and immune profile within the tumor microenvironment (TME).

Methods

In this study, we performed metagenomic sequencing of tumor and normal tissues from 61 non‐small cell lung cancer (NSCLC) patients and six patients with other lung diseases. In order to characterize the impact of the microbes in TME, the cytokine concentrations of 24 lung tumor and normal tissues were detected using a multiple cytokine panel.

Results

Our results showed that tumors had lower microbiota diversity than the paired normal tissues, and the microbiota of NSCLC was enriched in Proteobacteria, Firmicutes, and Actinobacteria. In addition, proinflammatory cytokines such as IL‐8, MIF, TNF‐ α, and so on, were significantly upregulated in tumor tissues.

Conclusion

We discovered a subset of bacteria linked to host inflammatory signaling pathways and, more precisely, to particular immune cells. We determined that lower airway microbiome dysbiosis may be linked to the disruption of the equilibrium of the immune system causing lung inflammation. The spread of lung cancer may be linked to specific bacteria.
Aging in the dermis: Fibroblast senescence and its significance
Authors: Zhang Jing , Yu Haoyue , Man Mao‐Qiang , Hu Lizhi
Published: December 2023

Skin aging is characterized by changes in its structural, cellular, and molecular components in both the epidermis and dermis. Dermal aging is distinguished by reduced dermal thickness, increased wrinkles, and a sagging appearance. Due to intrinsic or extrinsic factors, accumulation of excessive reactive oxygen species (ROS) triggers a series of aging events, including imbalanced extracellular matrix (ECM) homeostasis, accumulation of senescent fibroblasts, loss of cell identity, and chronic inflammation mediated by senescence‐associated secretory phenotype (SASP). These events are regulated by signaling pathways, such as nuclear factor erythroid 2‐related factor 2 (Nrf2), mechanistic target of rapamycin (mTOR), transforming growth factor beta (TGF‐β), and insulin‐like growth factor 1 (IGF‐1). Senescent fibroblasts can induce and accelerate age‐related dysfunction of other skin cells and may even cause systemic inflammation. In this review, we summarize the role of dermal fibroblasts in cutaneous aging and inflammation. Moreover, the underlying mechanisms by which dermal fibroblasts influence cutaneous aging and inflammation are also discussed.
Elevational patterns of species richness and community structure of understorey birds in an East African montane forest
Authors: Wambugu Geoffrey M. , Amakobe Bernard , Şekercioğlu Çağan H. , Githiru Mwangi
Published: December 2023

Mt. Kasigau is the northeastern most of the Eastern Arc Mountains global hotspot and harbours some endemic and threatened species, but little is known about bird community changes along its elevational gradient. We assessed the relationship between bird biodiversity metrics, season, human disturbance, elevation and temperature using mist‐netting data collected bi‐annually over a 10‐year period. Birds were sampled along the mountain's elevational gradient at four elevation levels (858, 1104, 1321 and 1547 m). Bird richness, diversity and evenness decreased with increasing altitude in both dry and wet seasons. Bird abundance declined with increasing elevation for the lower three elevation levels but peaked at the highest elevation. All diversity metrics were higher in the wet season compared to the dry season across all the years. Elevation had a greater effect on species assemblages than season, disturbance and temperature. Temperature had significant effects on abundance, diversity and richness, while disturbance had significant effects on diversity, evenness and richness. We conclude that bird assemblages in Mt. Kasigau are strongly shaped by elevational changes, while temperature and disturbance constitute important factors influencing bird conservation in the face of global warming. Our study highlights that elevation, disturbance and temperature influence bird assemblages along tropical elevational gradients.
Biologic use is not associated with postoperative complications in patients with Crohn's disease undergoing stoma reversion
Authors: Sun Zhenya , Song Tianrun , Guo Zhen , Cao Lei , Zhu Weiming , Li Yi
Published: December 2023

Purpose

Stoma creation is a common procedure in patients with Crohn's disease (CD), and early prophylaxis with biologics is recommended for high‐risk patients. However, the effect of biologic exposure on morbidity after stoma closure remains unknown. Therefore, this study aimed to investigate the impact of biologic use on the occurrence of complications in CD patients following stoma closure.

Methods

Consecutive patients diagnosed with CD who underwent ileostomy reversal at a tertiary care centre between 1 January 2013 and 1 December 2021, were included in the study. The primary outcome was the occurrence of 90‐day postoperative complications.

Results

The study included 347 eligible patients who underwent ileostomy reversal. There was no significant difference in terms of infectious complications, overall complications or length of postoperative stay between the biologic and non‐biologic groups. Multivariate logistic regression analysis identified several predictors of postoperative morbidity, including preoperative haemoglobin levels below 100 g/L, CRP levels above 10 mg/L, anastomotic site, ileostomy‐related infectious complications and albumin levels below 35 g/L.

Conclusions

This study demonstrated that the use of biologics is not associated with adverse outcomes. However, such as high CRP levels, ileostomy‐related infectious complications, hypoproteinemia, and hemoglobinemia, should be optimized prior to surgery to reduce postoperative morbidities.
TGF‐β signaling promotes desmoid tumor formation via CSRP2 upregulation
Authors: Li Yu , Fujishita Teruaki , Mishiro‐Sato Emi , Kojima Yasushi , Niu Yanqing , Taketo Makoto Mark , Urano Yuya , Sakai Tomohisa , Enomoto Atsushi , Nishida Yoshihiro , Aoki Masahiro
Published: December 2023

Desmoid tumors (DTs), also called desmoid‐type fibromatoses, are locally aggressive tumors of mesenchymal origin. In the present study, we developed a novel mouse model of DTs by inducing a local mutation in the Ctnnb1 gene, encoding β‐catenin in PDGFRA‐positive stromal cells, by subcutaneous injection of 4‐hydroxy‐tamoxifen. Tumors in this model resembled histologically clinical samples from DT patients and showed strong phosphorylation of nuclear SMAD2. Knockout of SMAD4 in the model significantly suppressed tumor growth. Proteomic analysis revealed that SMAD4 knockout reduced the level of Cysteine‐and‐Glycine‐Rich Protein 2 (CSRP2) in DTs, and treatment of DT‐derived cells with a TGF‐β receptor inhibitor reduced CSRP2 RNA levels. Knockdown of CSRP2 in DT cells significantly suppressed their proliferation. These results indicate that the TGF‐β/CSRP2 axis is a potential therapeutic target for DTs downstream of TGF‐β signaling.
Exploring the mechanism of bioactive components of Prunella vulgaris L. in treating hepatocellular carcinoma based on network pharmacology
Authors: Tu Huahua , Feng Yanqing , Wang Wei , Zhou Huadong , Cai Qinghe , Feng Yong
Published: December 2023

In traditional Chinese Medicine, Prunella vulgaris L. (PVL) is potentially effective in the treatment of some human malignancies including hepatocellular carcinoma (HCC). However, the detailed mechanism of action remains unclear. The purpose of this study was to decipher the constitutes of the bioactive ingredients of PVL, and its mechanism against HCC using network pharmacology and in vitro experiments. The bioactive components of PVL were obtained by Traditional Chinese Medicine System Pharmacology Database and Analysis platform database, and the targets of bioactive components of PVL was investigated by Swiss Target Prediction database. HCC related targets were obtained from GEO database, GeneCards database and DisGeNET database, and the gene ontology function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted for annotating the biological function of gene targets. A protein–protein interaction network was constructed using STRING database. Molecular docking of key bioactive ingredients was performed using AutoDock Vina. Cell proliferation and apoptosis were detected by cell counting kit‐8 and flow cytometry, respectively. The expression level of the target genes of PI3K/Akt pathway were detected by qPCR. In the present work, 11 bioactive components of PVL were screened out, which acted on 177 potential targets. In addition, 13,517 genes were strongly associated with HCC pathogenesis, of which 158 targets are overlapped with PVL's targets. KEGG results identified 39 signaling pathways closely associated with the 158 targets. Molecular docking showed that the main bioactive components of PVL, kaempferol, morin, quercetin, luteolin, and spinasterol, had good binding activity with the core proteins in cancer biology such as AKT1, EGFR, SRC, ESR1, and PPARG. In vitro assays showed that quercetin, one of the main components of PVL extracts effectively inhibited HCC cell proliferation, and promoted apoptosis, which may be associated with PI3K/AKT signaling pathway. In summary, PVL may regulate HCC progression by regulating core targets such as AKT1, EGFR, SRC, ESR1, and PPARG, and acting on PI3K‐Akt signaling pathway.
Relations between early majority language and socioemotional development in children with different language backgrounds
Authors: Huang Wei , Weinert Sabine , Volodina Anna
Published: December 2023

This study explored whether the directionality of the relation between majority language and various facets of socioemotional development (three to 5 years old) differs between children with different language backgrounds. 12,951 children (49% girls; 85% White, 6% Pakistani and Bangladeshi, 3% Black, 3% Mix, 2% Indian) from the British Millennium Cohort Study (2001–2006) were included in two‐time‐point cross‐lagged analyses. Models controlling for important covariates found a bidirectional association for monolinguals (βs = .05, −.07, −.04), a unidirectional effect of majority language on socioemotional difficulties for dual language learners (DLLs) speaking English and minority language(s) at home (β = .14), and a unidirectional effect of socioemotional strength on majority language for DLLs speaking only minority language(s) at home (β = −.17).
NAT10‐mediated ac4C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA
Authors: Ge Junbang , Wang Zhaoxia , Wu Ji
Published: December 2023

Cell fate determination in mammalian development is complex and precisely controlled and accumulating evidence indicates that epigenetic mechanisms are crucially involved. N4‐acetylcytidine (ac4C) is a recently identified modification of messenger RNA (mRNA); however, its functions are still elusive in mammalian. Here, we show that N‐acetyltransferase 10 (NAT10)‐mediated ac4C modification promotes ectoderm differentiation of human embryonic stem cells (hESCs) by acetylating nuclear receptor subfamily 2 group F member 1 (NR2F1) mRNA to enhance translation efficiency (TE). Acetylated RNA immunoprecipitation sequencing (acRIP‐seq) revealed that levels of ac4C modification were higher in ectodermal neuroepithelial progenitor (NEP) cells than in hESCs or mesoendoderm cells. In addition, integrated analysis of acRIP‐seq and ribosome profiling sequencing revealed that NAT10 catalysed ac4C modification to improve TE in NEP cells. RIP‐qRT‐PCR analysis identified an interaction between NAT10 and NR2F1 mRNA in NEP cells and NR2F1 accelerated the nucleus‐to‐cytoplasm translocation of yes‐associated protein 1, which contributed to ectodermal differentiation of hESCs. Collectively, these findings point out the novel regulatory role of ac4C modification in the early ectodermal differentiation of hESCs and will provide a new strategy for the treatment of neuroectodermal defects diseases.
Featured Cover
Authors: Gu Yuyuan , Hu Yan , Zhang Hao , Wang Sicheng , Xu Ke , Su Jiacan
Published: December 2023

The cover image is based on the Review Single‐cell RNA sequencing in osteoarthritis by Yuyuan Gu et al., https://doi.org/10.1111/cpr.13517.

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