bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulated neuroimmune interactions and sustained type I interferon signaling after human immunodeficiency virus type 1 infection of human iPSC derived microglia and cerebral organoids
Authors: Boreland Andrew J. , Stillitano Alessandro C. , Lin Hsin-Ching , Abbo Yara , Hart Ronald P. , Jiang Peng , Pang Zhiping P. , Rabson Arnold B. 
Published: October 2023

ABSTRACTHuman immunodeficiency virus type-1 (HIV-1) associated neurocognitive disorder (HAND) affects up to half of HIV-1 positive patients with long term neurological consequences, including dementia. There are no effective therapeutics for HAND because the pathophysiology of HIV-1 induced glial and neuronal functional deficits in humans remains enigmatic. To bridge this knowledge gap, we established a model simulating HIV-1 infection in the central nervous system using human induced pluripotent stem cell (iPSC) derived microglia combined with sliced neocortical organoids. Upon incubation with two replication-competent macrophage-tropic HIV-1 strains (JRFL and YU2), we observed that microglia not only became productively infected but also exhibited inflammatory activation. RNA sequencing revealed a significant and sustained activation of type I interferon signaling pathways. Incorporating microglia into sliced neocortical organoids extended the effects of aberrant type I interferon signaling in a human neural context. Collectively, our results illuminate the role of persistent type I interferon signaling in HIV-1 infected microglial in a human neural model, suggesting its potential significance in the pathogenesis of HAND.Highlights of the workHIV-1 productively infects iPSC-derived microglia and triggers inflammatory activation.HIV-1 infection of microglia results in sustained type I interferon signaling.Microglia infected by HIV-1 incorporate into sliced neocortical organoids with persistent type I interferon signaling and disease risk gene expression.
The intracellular domain of the epilepsy-related protein PCDH19 regulates spine density in cortical neurons
Authors: Newbold Sylvia A , Fox Ian WJ , Llinares-Benadero Cristina , Fabra-Beser Jaime , Stebleva Elizaveta , Gil-Sanz Cristina , Martinez-Garay Isabel 
Published: October 2023

ABSTRACTMutations in the X-linked cell adhesion molecule Protocadherin 19 (PCDH19) lead to epilepsy with cognitive impairment in heterozygous females and post-zygotic mosaic males. A complete absence of functional protein does not elicit symptoms, indicating a complex physiopathology and a dependence on cellular mosaicism. It is believed that mosaic expression of PCDH19 on neuronal membranes leads to defective cell-cell communication in the brain, but whether further roles beyond cell adhesion are critical for PCDH19 function in the cortex is currently unknown. Here, we characterize the proteolytic processing of PCDH19 in mouse cortical-like embryonic stem cell derived neurons and cortical lysates and show that its intracellular domain interacts with importins to be transported into the nucleus. RNAseq analysis of neurons derived from an engineered mouse embryonic stem cell line further indicates that the intracellular domain of PCDH19 leads to broad changes in the transcriptional landscape that are related to neuronal differentiation processes. Finally, we usein uteroelectroporation to provide the firstin vivodata about the role of this cleaved intracellular domain in upper layer cortical neurons, where it reduces spine density without affecting overall dendritic morphology. Because processing is activity dependent, our results suggest that PCDH19 could act as an activity sensor in a synapse to nucleus signaling pathway involved in synaptic homeostasis.
Streptococcus pyogenesCas9 ribonucleoprotein delivery for efficient, rapid and marker-free gene editing inTrypanosomaandLeishmania
Authors: Corinne Asencio , Perrine Hervé , Pauline Morand , Quentin Oliveres , Alexandra Morel Chloé , Valérie Prouzet-Mauleon , Marc Biran , Sarah Monic , Mélanie Bonhivers , Roy Robinson Derrick , Marc Ouellette , Loïc Rivière , Frédéric Bringaud , Emmanuel Tetaud 
Published: October 2023

SUMMARYKinetoplastids are unicellular eukaryotic flagellated parasites found in a wide range of hosts within the animal and plant kingdoms. They are known to be responsible in humans for African sleeping sickness (Trypanosoma brucei), Chagas disease (Trypanosoma cruzi), and various forms of leishmaniasis (Leishmaniaspp.), as well as several animal diseases with important economic impact (African trypanosomes, includingT. congolense). Understanding the biology of these parasites necessarily implies the ability to manipulate their genomes. In this study, we demonstrate that transfection of a ribonucleoprotein complex, composed of recombinantStreptococcus pyogenesCas9 (SpCas9) and anin vitro-synthesized guide RNA, results in rapid and efficient genetic modifications of trypanosomatids, in marker-free conditions. This approach was successfully developed to inactivate, delete and mutate candidate genes in various stages of the life cycle ofT. bruceiandT. congolense, andLeishmaniapromastigotes. The functionality ofSpCas9 in these parasites now provides, to the research community working on these parasites, a rapid and efficient method of genome editing, without requiring plasmid construction and selection by antibiotics. Importantly, this approach is adaptable to any wild-type parasite, including field isolates.
Incorporation of collagen intoPseudomonas aeruginosaandStaphylococcus aureusbiofilms impedes phagocytosis by neutrophils
Authors: Zhou Xuening , Wells Marilyn J. , Gordon Vernita D. 
Published: October 2023

AbstractBiofilms are communities of microbes embedded in a matrix of extracellular polymeric substances (EPS). Matrix components can be produced by biofilm organisms and can also originate from the environment and then be incorporated into the biofilm. For example, we have recently shown that collagen, a host-produced protein that is abundant in many different infection sites, can be taken up into the biofilm matrix, altering biofilm mechanics. The biofilm matrix protects bacteria from clearance by the immune system, and some of that protection likely arises from the mechanical properties of the biofilm.Pseudomonas aeruginosaandStaphylococcus aureusare common human pathogens notable for forming biofilm infections in anatomical sites rich in collagen. Here, we show that the incorporation of Type I collagen intoP. aeruginosaandS. aureusbiofilms significantly hinders phagocytosis of biofilm bacteria by human neutrophils. However, enzymatic treatment with collagenase, which breaks down collagen, can partly or entirely negate the protective effect of collagen and restore the ability of neutrophils to engulf biofilm bacteria. From these findings, we suggest that enzymatic degradation of host materials may be a potential way to compromise biofilm infections and enhance the efficacy of the host immune response without promoting antibiotic resistance. Such an approach might be beneficial both in cases where the infecting species is known and also in cases wherein biofilm components are not readily known, such as multispecies infections or infections by unknown species.
SCFcyclin F- EXO1 axis controls cell cycle dependent execution of double strand break repair
Authors: Yang Hongbin , Fouad Shahd , Smith Paul , Bae Eun Young , Ji Yu , Ess Ava Van , Buffa Francesca M , Fisher Roman , Vendrell Iolanda , Kessler Benedikt M , D’Angiolella Vincenzo 
Published: October 2023

AbstractUbiquitination is a crucial post-translational modification required for the proper repair of DNA double-strand breaks (DSBs) induced by ionising radiation (IR). DSBs are mainly repaired through homologous recombination (HR) when template DNA is present and non-homologous end joining (NHEJ) in its absence. Additionally, microhomology-mediated end joining (MMEJ) and single strand annealing (SSA) provide back-up DSBs repair pathways. However, the mechanisms controlling their use remain poorly understood. By employing a high-resolution CRISPR screen of the ubiquitin system after IR, we systematically uncover genes required for cell survival and elucidate a critical role of the E3 ubiquitin ligase SCFcyclinFin cell cycle-dependent DSB repair. We show that SCFcyclinF-mediated EXO1 degradation prevents DNA end resection in mitosis, allowing MMEJ to take place. Moreover, we identify a conserved cyclin F recognition motif, distinct from the one used by other cyclins, with broad implications in cyclin specificity for cell cycle control.
Spatial control of the APC/C ensures the rapid degradation of Cyclin B1
Authors: Cirillo Luca , Young Rose , Veerapathiran Sapthaswaran , Roberti Annalisa , Martin Molly , Abubacar Azzah , Perosa Camilla , Coates Catherine , Muhammad Reyhan , Roumeliotis Theodoros I. , Choudhary Jyoti S. , Alfieri Claudio , Pines Jonathon 
Published: October 2023

ABSTRACTThe proper control of mitosis depends on the ubiquitin-mediated degradation of the right mitotic regulator at the right time. This is under the control of the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase that is regulated by the Spindle Assembly Checkpoint (SAC). The Checkpoint prevents the APC/C from recognizing Cyclin B1, the essential anaphase and cytokinesis inhibitor, until all chromosomes are attached to the spindle. Once chromosomes are attached, Cyclin B1 is rapidly degraded to enable chromosome segregation and cytokinesis. We have a good understanding of how the SAC inhibits the APC/C, but relatively little is known about how the APC/C recognises Cyclin B1 as soon as the SAC is turned off. Here, by combining live cell imaging,in vitroreconstitution, biochemistry, and structural analysis by cryo-electron microscopy, we provide evidence that the rapid recognition of Cyclin B1 in metaphase requires spatial regulation of the APC/C. Using fluorescence cross correlation spectroscopy, we find that Cyclin B1 and the APC/C primarily interact at the mitotic apparatus. We further show that this is because Cyclin B1, like the APC/C, binds to nucleosomes, and identify an ‘arginine-anchor’ in the N-terminus as necessary and sufficient for binding to the nucleosome. Mutating the nucleosome binding motif on Cyclin B1 reduces its interaction with APC/C and delays its degradation, and cells with the mutant, non-nucleosome-binding Cyclin B1 become aneuploid, demonstrating the physiological relevance of our findings. Together, our data demonstrate that mitotic chromosomes constitute a platform to promote the efficient interaction between Cyclin B1 and APC/C and ensure the timely degradation of Cyclin B1 and genomic stability.
Activation of the mitochondrial unfolded protein response regulates the formation of stress granules
Authors: Lopez-Nieto Marta , Sun Zhaozhi , Relton Emily , Safakli Rahme , Freibaum Brian D. , Taylor J Paul , Ruggieri Alessia , Smyrnias Ioannis , Locker Nicolas 
Published: October 2023

AbstractTo rapidly adapt to harmful changes to their environment, cells activate the integrated stress response (ISR). This results in an adaptive transcriptional and translational rewiring, and the formation of biomolecular condensates named stress granules (SGs), to resolve stress. In addition to this first line of defence, the mitochondrial unfolded protein response (UPRmt) activates a specific transcriptional programme to maintain mitochondrial homeostasis. We present evidence that SGs and UPRmtpathways are intertwined and communicate. UPRmtinduction results in eIF2α phosphorylation and the initial and transient formation of SGs, which subsequently disassemble. The induction of GADD34 during late UPRmtprotects cells from prolonged stress by impairing further assembly of SGs. Furthermore, mitochondrial functions and cellular survival are enhanced during UPRmtactivation when SGs are absent, suggesting that UPRmt-induced SGs have an adverse effect on mitochondrial homeostasis. These findings point to a novel crosstalk between SGs and the UPRmtthat may contribute to restoring mitochondrial functions under stressful conditions.Summary statementWe describe a novel crosstalk between the mitochondrial unfolded protein response and the integrated stress response involving stress granules that protects cells from further stress.
Identification and characterization of intermediate states in mammalian neural crest cell epithelial to mesenchymal transition and delamination
Authors: Zhao Ruonan , Moore Emma L. , Gogol Madelaine M , Unruh Jay R. , Yu Zulin , Scott Allison , Wang Yan , Rajendran Naresh Kumar , Trainor Paul A. 
Published: October 2023

AbstractEpithelial to mesenchymal transition (EMT) is a cellular process that converts epithelial cells to mesenchymal cells with migratory potential in both developmental and pathological processes. Although originally considered a binary event, EMT in cancer progression involves intermediate states between a fully epithelial and a fully mesenchymal phenotype, which are characterized by distinct combinations of epithelial and mesenchymal markers. This phenomenon has been termed epithelial to mesenchymal plasticity (EMP), however, the intermediate states remain poorly described and it’s unclear whether they exist during developmental EMT. Neural crest cells (NCC) are an embryonic progenitor cell population that gives rise to numerous cell types and tissues in vertebrates, and their formation is a classic example of developmental EMT. An important feature of NCC development is their delamination from the neuroepithelium via EMT, following which NCC migrate throughout the embryo and undergo differentiation. NCC delamination shares similar changes in cellular state and structure with cancer cell invasion. However, whether intermediate states also exist during NCC EMT and delamination remains unknown. Through single cell RNA sequencing, we identified intermediate NCC states based on their transcriptional signature and then spatially defined their locations in situ in the dorsolateral neuroepithelium. Our results illustrate the progressive transcriptional and spatial transitions from premigratory to migratory cranial NCC during EMT and delamination. Of note gene expression and trajectory analysis indicate that distinct intermediate populations of NCC delaminate in either S phase or G2/M phase of the cell cycle, and the importance of cell cycle regulation in facilitating mammalian cranial NCC delamination was confirmed through cell cycle inhibition studies. Additionally, transcriptional knockdown revealed a functional role for the intermediate stage markerDlc1in regulating NCC delamination and migration. Overall, our work identifying and characterizing the intermediate cellular states, processes, and molecular signals that regulate mammalian NCC EMT and delamination furthers our understanding of developmental EMP and may provide new insights into mechanisms regulating pathological EMP.
Designing aerodynamic devices for UAV – lessons learned
Authors: Mieloszyk Jacek , Tarnowski Andrzej , Goetzendorf-Grabowski Tomasz 
Published: October 2023

Purpose
Designing new aircraft that are state-of-the-art and beyond always requires the development of new technologies. This paper aims to present lessons learned while designing, building and testing new UAVs in the configuration of the flying wing. The UAV contains a number of aerodynamic devices that are not obvious solutions and use the latest manufacturing technology achievements, such as 3D printing.

Design/methodology/approach
The design solutions were applied on an airworthy aircraft and checked during test flights. The process was first conducted on the smaller UAV, and based on the test outcomes, improvements were made and then applied on the larger version of the UAV, where they were verified.

Findings
A number of practical findings were identified. For example, the use of 3D printing technology for manufacturing integrated pressure ports, investigation of the adverse yaw effect on the flying wing configuration and the effectiveness of winglet rudders in producing yawing moment.

Practical implications
All designed devices were tested in practice on the flying aircraft. It allowed for improved aircraft performance and handling characteristics. Several of the technologies used improved the speed and quality of aerodynamic device design and manufacturing, which also influences the reliability of the aircraft.

Originality/value
The paper presents how 3D printing technology can be utilized for manufacturing of aerodynamic devices. Specially developed techniques for control surface design, which can affect adverse yaw problem and aircraft handling characteristics, were described.
Collaborative technology in a hybrid learning context: exploring feeling at ease and perceived learning among college students
Authors: Hopkins Matt , Lin Meng-Hsien , Nariswari Angeline 
Published: October 2023

PurposeThis study explores collaborative technology's effectiveness in facilitating learning in a hybrid (synchronous face-to-face and asynchronous virtual) context. In particular, the study explores the critical role of students' feeling-at-ease, including its drivers and impact on their perception of the technology.Design/methodology/approachThe study included a classroom intervention in which a collaborative technology, i.e. VoiceThread, was implemented in a hybrid learning context. Online surveys, which included quantitative and qualitative components, were administered at the start and end of the semester to capture student perceptions and experiences with the technology.FindingsStudents who felt more at ease assessed the collaborative technology more positively. While extraversion was marginally associated with initial feeling at ease, technology anxiety was not. When using the technology to post content, students who felt more at ease preferred using audio or video over text. Students' perception of the importance of technology in facilitating their learning was a key mediator in the relationship between feeling less at ease and future intention to use the collaborative technology.Originality/valueThe paper investigates the implementation of a collaborative technology in a hybrid learning context, highlighting the critical role of feeling at ease in impacting its acceptance.
Refugees and asylum seekers in informal and precarious jobs: early labour market insertion from the perspectives of professionals and volunteers
Authors: Dimitriadis Iraklis 
Published: October 2023

PurposeThis article aims to explore the engagement of refugees and asylum seekers (RAS) in informal and precarious jobs from a civil society actors' perspective. Despite a burgeoning literature on refugee integration and a focus on institutional integration programmes, little is known about the early insertion of RAS into informal and precarious employment as an alternative to subsidised integration programmes, when these are available.Design/methodology/approachThis article draws on rich qualitative data collected through in-depth interviews with social workers, volunteers and other professionals supporting migrants.FindingsData analysis shows that migrants' insertion in informal jobs and their rejection of integration programmes may be the result of people's need to access financial capital to cover actual and future needs. Although such an engagement may be criticised for hampering RAS’ integration, it can be seen as an important source of agency against insecurity surrounding one's legal status.Originality/valueThis article highlights the importance of legal status precarity in shaping informal workers' agency and perceptions of them, opening up a debate on the relevance of informal work in terms of long-term integration and future migration trajectories.
Multiple interaction strategies for mobile robots based on improved dynamic window approach in unknown dynamic environments
Authors: He Li , Zhang Shuai , Zhang Heng , Yuan Liang 
Published: October 2023

Purpose
The purpose of this paper is to solve the problem that mobile robots are still based on reactive collision avoidance in unknown dynamic environments leading to a lack of interaction with obstacles and limiting the comprehensive performance of mobile robots. A dynamic window approach with multiple interaction strategies (DWA-MIS) is proposed to solve this problem.

Design/methodology/approach
The algorithm firstly classifies the moving obstacle movement intention, based on which a rule function is designed to incorporate positive incentives to motivate the robot to make correct avoidance actions. Then, the evaluation mechanism is improved by considering the time cost and future information of the environment to increase the motion states. Finally, the optimal objective function is designed based on genetic algorithm to adapt to different environments with time-varying multiparameter optimization.

Findings
Faced with obstacles in different states, the mobile robot can choose a suitable interaction strategy, which solves the limitations of the original DWA evaluation function and avoids the defects of reactive collision avoidance. Simulation results show that the algorithm can efficiently adapt to unknown dynamic environments, has less path length and iterations and has a high comprehensive performance.

Originality/value
A DWA-MIS is proposed, which increases the interaction capability between mobile robots and obstacles by improving the evaluation function mechanism and broadens the navigation strategy of DWA at a lower computational cost. After real machine verification, the algorithm has a high comprehensive performance based on real environment and provides a new idea for local path planning methods.
Does a conduct disorder factor increment the capacity of the Youth Psychopathic Traits Inventory-Short to predict criminal recidivism?
Authors: Pechorro Pedro , Gomide Paula , DeLisi Matt , Simões Mário 
Published: October 2023

Purpose
Recent developments in the psychometric assessment of youth psychopathic traits suggest that the inclusion of a conduct disorder (CD) factor to the traditional three factors of the psychopathy construct may improve the incremental validity of these measures. The purpose of the current study is to examine whether the addition of a CD factor incrementally improves the ability of the Youth Psychopathic Traits Inventory Short version (YPI-S) to predict criminal recidivism.

Design/methodology/approach
A longitudinal quantitative research design was used with a sample detained male youth (N = 214, Mage = 16.4 years, SDage = 1.3 years).

Findings
Results using the area under the curve analysis suggest that the inclusion of a CD factor slightly improves the capacity of the YPI-S to predict one-year general criminal recidivism, but it does not significantly increase its capacity to predict violent criminal recidivism. Results also indicate that a CD scale outperforms the YPI-S, even with an additional CD factor included, in terms of predicting one-year general and violent recidivism.

Practical implications
Self-reported youth psychopathic trait measures, even those that include a CD factor as a fourth factor, should be used with caution when the aim is to predict youth criminal recidivism.

Originality/value
To the best of the authors’ knowledge, this is the first study using a self-reported youth psychopathic traits measure with a CD factor to examine youth criminal recidivism.