bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of R5 Pyocin in the Predominance of High-RiskPseudomonas aeruginosaIsolates
Authors: Zhang Liyang , Xu Qi , Tan Filemon C , Deng Yanhan , Hakki Morgan , Shelburne Samuel A. , Kirienko Natalia V. 
Published: October 2024

AbstractInfections with antimicrobial resistant pathogens, such asPseudomonas aeruginosa,are a frequent occurrence in healthcare settings. HumanP. aeruginosainfections are predominantly caused by a small number of sequence types (ST), such as ST235, ST111, and ST175. Although ST111 is recognized as one of the most prevalent high-riskP. aeruginosaclones worldwide and frequently exhibits multidrug-resistant or extensively drug-resistant phenotypes, the basis for this dominance remains unclear. In this study, we used a genome-wide transposon insertion library screen to discover that the competitive advantage of ST111 strains over certain non-ST111 strains is through production of R pyocins. We confirmed this finding by showing that competitive dominance was lost by ST111 mutants with R pyocin gene deletions. Further investigation showed that sensitivity to ST111 R pyocin (specifically R5 pyocin) is caused by deficiency in the O-antigen ligasewaaL, which leaves lipopolysaccharide (LPS) bereft of O antigen, enabling pyocins to bind the LPS core. In contrast, sensitivity ofwaaLmutants to R1 or R2 pyocins depended on additional genomic changes. In addition, we found the PA14 mutants in lipopolysaccharide biosynthesis (waaL,wbpL,wbpM) that cause high susceptibility to R pyocins also exhibit poor swimming motility. Analysis of 5,135 typedP. aeruginosastrains revealed that several international, high-risk sequence types (including ST235, ST111, and ST175) are enriched for R5 pyocin production, indicating a correlation between these phenotypes and suggesting a novel approach for evaluating risk from emerging prevalentP. aeruginosastrains. Overall, our study sheds light on the mechanisms underlying the dominance of ST111 strains and highlighting the role ofwaaLin extending spectrum of R pyocin susceptibility.
Structural and molecular basis of FAN1 defects in promoting Huntington’s disease
Authors: Li F. , Phadte A. , Bhatia M. , Barndt S. , Monte Carlo A. R. , Hou C-F. D. , Yang R. , Strock S. , Pluciennik A. 
Published: October 2024

ABSTRACTFAN1 is a DNA dependent nuclease whose proper function is essential for maintaining human health. For example, a genetic variant in FAN1, Arg507 to His hastens onset of Huntington’s disease, a repeat expansion disorder for which there is no cure. How the Arg507His mutation affects FAN1 structure and enzymatic function is unknown. Using cryo-EM and biochemistry, we have discovered that FAN1 arginine 507 is critical for its interaction with PCNA, and mutation of Arg507 to His attenuates assembly of the FAN1-PCNA on a disease-relevant extrahelical DNA extrusions formed within DNA repeats. This mutation concomitantly abolishes PCNA-FAN1-dependent cleavage of such extrusions, underscoring the importance of PCNA to the genome stabilizing function of FAN1. These results unravel the molecular basis for a specific mutation in FAN1 that dramatically hastens the onset of Huntington’s disease.
Striatal cell-type–specific molecular signatures reveal therapeutic targets in a model of dystonia
Authors: Roman Kaitlyn M. , Dinasarapu Ashok R. , Cherian Suraj , Fan Xueliang , Donsante Yuping , Aravind Nivetha , Chan C. Savio , Jinnah H.A. , Hess Ellen J. 
Published: October 2024

AbstractStriatal dysfunction is implicated in many forms of dystonia, including idiopathic, inherited and iatrogenic dystonias. The striatum is comprised largely of GABAergic spiny projection neurons (SPNs) that are defined by their long-range efferents. Direct SPNs (dSPNs) project to the internal globus pallidus/substantia nigra reticulata whereas indirect pathway SPNs (iSPNs) project to the external pallidum; the concerted activity of both SPN subtypes modulates movement. Convergent results from genetic, imaging and physiological studies in patients suggest that abnormalities of both dSPNs and iSPNs contribute to the expression of dystonia, but the molecular adaptations underlying these abnormalities are not known. Here we provide a comprehensive analysis of SPN cell-type–specific molecular signatures in a model of DOPA-responsive dystonia (DRD mice), which is caused by gene defects that reduce dopamine neurotransmission, resulting in dystonia that is specifically associated with striatal dysfunction. Individually profiling the translatome of dSPNs and iSPNs using translating ribosome affinity purification with RNA-seq revealed hundreds of differentially translating mRNAs in each SPN subtype in DRD mice, yet there was little overlap between the dysregulated genes in dSPNs and iSPNs. Despite the paucity of shared adaptations, a disruption in glutamatergic signaling was predicted for both dSPNs and iSPNs. Indeed, we found that both AMPA and NMDA receptor-mediated currents were enhanced in dSPNs but diminished in iSPNs in DRD mice. The pattern of mRNA dysregulation was specific to dystonia as the adaptations in DRD mice were distinct from those in parkinsonian mice where the dopamine deficit occurs in adults, suggesting that the phenotypic outcome is dependent on both the timing of the dopaminergic deficit and the SPN-specific adaptions. We leveraged the unique molecular signatures of dSPNs and iSPNs in DRD mice to identify biochemical mechanisms that may be targets for therapeutics, including LRRK2 inhibition. Administration of the LRRK2 inhibitor MLi-2 ameliorated the dystonia in DRD mice suggesting a novel target for therapeutics and demonstrating that the delineation of cell-type–specific molecular signatures provides a powerful approach to revealing both CNS dysfunction and therapeutic targets in dystonia.
Unveiling mechanical interactions between cell division and extracellular matrix in human colonic epithelium organoids: A 4D study using DVC
Authors: Magne L. , Pottier T. , Michel D. , Laussu J. , Bonnet D. , Alric L. , Recher G. , Segonds S. , Bugarin F. , Ferrand A. 
Published: October 2024

AbstractCell division is a major event in tissue homeostasis, enabling renewal and regeneration. Stem cells, in particular, play an important role in this homeostasis, thanks to their ability to perform symmetric or asymmetric cell divisions. To study cell division, the human colon epithelium represents a model of choice due to its rapid renewal and therefore high proliferative potential. Currently, studying the live mechanical interactions between the epithelium and its matrixin vivois challenging due to the lack of suitable methods. 3D human colon organoids seeded in Matrigel® are good models for this purpose as, from isolated stem cells, they recapitulate the tissue architecture organization and properties. This culture set-up also allows to study the matrix displacements around the organoid.Here, we studied the impact of cell division within the colonic epithelium on the extracellular matrix. We performed and validated an original experimental and analytical process with a 3D time-lapse confocal microscopy to follow cell mitosis and matrix movements on which we performed Digital Volume Correlation. We showed that these two different types of cell division impact the matrix differently with the asymmetric divisions causing a mainly uniaxial displacement, whereas symmetric ones involved a multiaxial and more important one.
Acute GARP depletion disrupts vesicle transport, leading to severe defects in sorting, secretion, and O-glycosylation
Authors: Khakurel Amrita , Pokrovskaya Irina , Lupashin Vladimir V. 
Published: October 2024

AbstractThe GARP complex is an evolutionarily conserved protein complex proposed to tether endosome-derived vesicles at the trans-Golgi network. While prolonged depletion of GARP leads to severe trafficking and glycosylation defects, the primary defects linked to GARP dysfunction remain unclear. In this study, we utilized the mAID degron strategy to achieve rapid degradation of VPS54 in human cells, acutely disrupting GARP function. This resulted in the partial mislocalization and degradation of a subset of Golgi-resident proteins, including TGN46, ATP7A, TMEM87A, CPD, C1GALT1, and GS15. Enzyme recycling defects led to the early onset of O-glycosylation abnormalities. Additionally, while the secretion of fibronectin and cathepsin D was altered, mannose-6-phosphate receptors were largely unaffected. Partial displacement of COPI, AP1, and GGA coats caused a significant accumulation of vesicle-like structures and large vacuoles. Electron microscopy detection of GARP-dependent vesicles, along with the identification of specific cargo proteins, provides direct experimental evidence of GARP’s role as a vesicular tether. We conclude that the primary defects of GARP dysfunction involve vesicular coat mislocalization, accumulation of GARP-dependent vesicles, degradation and mislocalization of specific Golgi proteins, and O-glycosylation defects.
Molecular states underlying neuronal cell type development and plasticity in the whisker cortex
Authors: Butrus Salwan , Monday Hannah R. , Yoo Christopher J. , Feldman Daniel E. , Shekhar Karthik 
Published: October 2024

ABSTRACTMouse whisker somatosensory cortex (wS1) is a major model system to study the experience-dependent plasticity of cortical neuron physiology, morphology, and sensory coding. However, the role of sensory experience in regulating neuronal cell type development and gene expression in wS1 remains poorly understood. We assembled and annotated a transcriptomic atlas of wS1 during postnatal development comprising 45 molecularly distinct neuronal types that can be grouped into eight excitatory and four inhibitory neuron subclasses. Using this atlas, we examined the influence of whisker experience from postnatal day (P) 12, the onset of active whisking, to P22, on the maturation of molecularly distinct cell types. During this developmental period, when whisker experience was normal, ∼250 genes were regulated in a neuronal subclass-specific fashion. At the resolution of neuronal types, we found that only the composition of layer (L) 2/3 glutamatergic neuronal types, but not other neuronal types, changed substantially between P12 and P22. These compositional changes resemble those observed previously in the primary visual cortex (V1), and the temporal gene expression changes were also highly conserved between the two regions. In contrast to V1, however, cell type maturation in wS1 is not substantially dependent on sensory experience, as 10-day full-face whisker deprivation did not influence the transcriptomic identity and composition of L2/3 neuronal types. A one-day competitive whisker deprivation protocol also did not affect cell type identity but induced moderate changes in plasticity-related gene expression. Thus, developmental maturation of cell types is similar in V1 and wS1, but sensory deprivation minimally affects cell type development in wS1.Highlights-A single-nucleus transcriptomic atlas of the whisker somatosensory cortex (wS1) during early postnatal development-Different neuronal subclasses in wS1 show distinct developmental gene expression changes-The composition of L2/3 glutamatergic neurons changes between the second and the third postnatal week-Developmental gene expression and cell type changes are conserved between wS1 and the primary visual cortex (V1)-Unlike V1, these changes are not affected by prolonged sensory deprivation-Brief whisker deprivation induces subclass-specific activity-dependent gene expression in a whisker column-specific fashion
Genetically-encoded markers for confocal visualization of single dense core vesicles
Authors: Yu Junwei , Zhang Yunpeng , Clements Kelsey , Chen Nannan , Griffith Leslie C. 
Published: October 2024

AbstractNeuronal dense core vesicles (DCVs) store and release a diverse array of neuromodulators, trophic factors and bioamines. The analysis of single DCVs has largely been possible only using electron microscopy, which makes understanding cargo segregation and DCV heterogeneity difficult. To address these limitations, we developed genetically-encoded markers for DCVs that can be used in combination with standard immunohistochemistry and expansion microscopy, to enable single-vesicle resolution with confocal microscopy.
Cholecystokinin-expressing GABA neurons elicit long-term potentiation in the cortical inhibitory synapses and attenuate sound-shock associative memory
Authors: Zhang Ge , Pang Kwok Kin , Chen Xi , Huang Fengwen , He Jufang 
Published: October 2024

AbstractNeuronal interactions between inhibitory and excitatory neurons play a pivotal role in regulating the balance of excitation and inhibition in the central nervous system (CNS). Consequently, the efficacy of inhibitory/excitatory synapses profoundly affects neural network processing and overall neuronal functions. Here, we describe a novel form of long-term potentiation (LTP) induced at cortical inhibitory synapses and its behavioral consequences. We show that high-frequency laser stimulation (HFLS) of GABAergic neurons elicit inhibitory LTP (i-LTP) in pyramidal neurons of the auditory cortex (AC). The selective activation of cholecystokinin-expressing GABA (GABACCK) neurons is essential for the formation of HFLS-induced i-LTP, rather than the classical parvalbumin (PV) neurons and somatostatin (SST) neurons. Intriguingly, i-LTP can be evoked in the AC by adding the exogenous neuropeptide CCK when PV neurons and SST neurons are selectively activated in PV-Cre and SST-Cre mice, respectively. Additionally, we discovered that low-frequency laser stimulation (LFLS) of PV neurons paired with HFLS of GABACCKneurons potentiates the inhibitory effect of PV interneurons on pyramidal neurons, thereby generating heterosynaptic i-LTP in the AC. Notably, light activation of GABACCKneurons in CCK-Cre mice significantly attenuates sound-shock associative memory, while stimulation of PV neurons does not affect this memory in PV-Cre mice. In conclusion, these results demonstrate a critical mechanism regulating the excitation-inhibition balance and modulating learning and memory in cortical circuits. This mechanism might serve as a potential target for the treatment of neurological disorders, including epilepsy and Alzheimer’s disease.
Subdiffusion of heavy quarks in hot QCD matter by the fractional Langevin equation
Authors: Prakash Jai 
Published: October 2024

The subdiffusion phenomena are studied for heavy quarks dynamics in the hot QCD matter. Our approach aims to provide a more realistic description of heavy quark dynamics through detailed theoretical analyses and numerical simulations, utilizing the fractional Langevin equation framework with the Caputo fractional derivative. I present numerical schemes for the fractional Langevin equation for subdiffusion and calculate the time evolution mean squared displacement and mean squared momentum of the heavy quarks. My results indicate that the mean squared displacements of the heavy quarks for the subdiffusion process deviate from a linear relationship with time. Further, I calculate the normalized momentum correlation function, kinetic energy, and momentum spread. Finally, I show the effect of subdiffusion on experimental observables, the nuclear modification factor.

Published by the American Physical Society
2024
Dynamics of particle-particle correlations and the ridge effect in proton-proton collisions
Authors: Calé G. , Chachamis G. , Vera A. Sabio 
Published: October 2024

In high-energy particle physics, the study of particle-particle correlations in proton-proton and heavy-ion collisions constitutes a pivotal frontier in the effort to understand the fundamental dynamics of the strong force. To the best of our knowledge, we employ for the first time the Balitsky-Fadin-Kuraev-Lipatov dynamics implemented in a Monte Carlo code in momentum space to compute final-state correlations in proton-proton collisions. Our present work aims to investigate whether the particular dynamics of the high-energy limit of QCD can contribute to the long-range rapidity correlations and the enigmatic ridge effect in proton-proton collisions.

Published by the American Physical Society
2024
An exploratory study on a comprehensive set of criteria for facade assessment
Authors: Zekri Amirhossein , Tarkashvand Abbas , Ekhlassi Ahmad 
Published: October 2024

Purpose
The presentation of all required criteria that a facade should fulfill needs to be revised, particularly considering novel perspectives on facade. This study aims to fill this need because leaving it unsolved leads the specialists to evaluate and design facades based on insufficient data resulting in imprecise decisions in both areas.

Design/methodology/approach
An exploratory study was conducted based on library resources to identify and extract the criteria, which were coded openly and axially, and categorized via a new standpoint. Shannon method was also used to analyze categories’ frequencies.

Findings
In total, 42 criteria were found and organized in five categories: “Environmental Aspects,” “Social Impacts,” “Economic Aspects,” “Efficiency and Effectiveness” and “Technical Issues.” This study adds 20 criteria, including “Natural Resource Depletion” and “Clients’ Preferences,” to facade assessment criteria compared to previous studies. Compared to similar research, “Technical Aspects” is augmented to this field's categorizations, whereas “Social Impacts” and “Environmental Aspects” are provided in a more extensive way.

Research limitations/implications
The research proceeded until theoretical saturation; therefore, there is no claim to be the most comprehensive. The findings are instrumental to professionals for making practical decisions. The concentration and frequency of the literature will offer an insight to academics about the pioneering fields of facade development.

Originality/value
This study presents a comprehensive and up-to-date set of facade assessment criteria based on new approaches that see facade as a multifunctional component that must address various requirements beyond aesthetics.
Building employability in PASS leaders through peer-assisted study sessions (PASS) programs
Authors: Despotovic William Vuk , McPhail Ruth , Schmidtke David 
Published: October 2024

PurposeThe peer-assisted study sessions program (PASS) – variously known as supplemental instruction, peer mentoring and peer-assisted learning – is regarded as a global phenomenon in academic support interventions and has well established presence in higher education. The purpose of this study was to add to the body of knowledge of how PASS may add value to the employability of the student leaders, in relation to the CareerEDGE model.Design/methodology/approachThis qualitative research was based on interviews from a sample of 18 former PASS leaders who have since obtained employment.FindingsFindings demonstrate that being a PASS leader enhanced many of their competencies as defined by CareerEDGE model, for example subject related knowledge, interpersonal skills and some generic skills. However, many of the reported competency enhancements led to unexpected future career advancement.Research limitations/implicationsThis study contributes to the body of knowledge relating to how PASS may add value to the employability of student leaders in relation to the CareerEDGE model using a sample of leaders who have already graduated and have obtained employment. Limitations of this study include: lack of generalisability of small geographically isolated sample; coding and analsysis not comparing findings from different demographic groups; only explores individual perceptions and relies on self-reported data.Practical implicationsThe results of this study have implications for the development of future PASS programs and other similar academic support interventions. Given the global prevalence of such programs in higher education institutions, this research may have wide-scale transferability. Insights from this paper will allow future PASS leaders to proactively reflect and evaluate their experience and increase their confidence in pursuing their employment opportunities.Originality/valueWhile there is much understanding on the role that PASS has in improving students grades and in improving retention rates, less is known about the value of this experience on improving student employability, and little attempt has been made in examining this within relevant employability models post-employment.
A grey incidence-based algorithm for optimization of accelerated degradation test
Authors: Zhang Weikang , Gu Huiru , Wu Sainan , Zhong Shusen , Yang Jing , Luan Huiqin , Li Qi 
Published: October 2024

PurposeThe purpose of this paper is to optimize the degradation test for products subject to multiple types of inherent stresses and external random shocks. The mechanism that shows how the variables to be optimized influence the considered multiple objectives is also aimed to be explored by using the grey incidence analysis (GIA) model.Design/methodology/approachThe Gamma process is employed to model the influences of different types of stresses and external random shocks. The GIA model is introduced to transfer multiple considered objectives as a comprehensive degree of grey incidence. The particle swarm optimization is integrated to search the globally optimal value of the characteristic variables to be optimized.FindingsThe acceleration of tested stresses and external random shocks both make the engineering systems become more vulnerable to the inherent degradation. And, the Kriging model can provide guidance of searching the optimal values of test characteristic variables and mitigate the computation burden. The grey incidence model can make the optimization focused and improve the optimality of objective values.Originality/valueThe proposed method can effectively overcome the drawbacks brought by the limitation of test data and can specify the dependence strength between the inherent degradation and external random shock. The computation cost and accuracy of optimization can be simultaneously ensured by the proposed model.