bluuebunny/crossref_metadata_2025_split huggingface dataset:
A functional screen for ubiquitin regulation identifies an E3 ligase secreted byPseudomonas aeruginosa
Authors: Roberts Cameron G. , Kaur Supender , Ogden Aaron J. , Divine Michael E. , Warren Gus D. , Kang Donghoon , Kirienko Natalia V. , Geurink Paul P. , Mulder Monique P.C. , Nakayasu Ernesto S. , McDermott Jason E. , Adkins Joshua N. , Aballay Alejandro , Pruneda Jonathan N. 
Published: September 2024

ABSTRACTUbiquitin signaling controls many aspects of eukaryotic biology, including targeted protein degradation and immune defense. Remarkably, invading bacterial pathogens have adapted secreted effector proteins that hijack host ubiquitination to gain control over host responses. These ubiquitin-targeted effectors can exhibit, for example, E3 ligase or deubiquitinase activities, often without any sequence or structural homology to eukaryotic ubiquitin regulators. Such convergence in function poses a challenge to the discovery of additional bacterial virulence factors that target ubiquitin. To overcome this, we have developed a workflow to harvest natively secreted bacterial effectors and functionally screen them for ubiquitin regulatory activities. After benchmarking this approach on diverse ligase and deubiquitinase activities fromSalmonellaTyphimurium, EnteropathogenicEscherichia coli, andShigella flexneri, we applied it to the identification of a cryptic E3 ligase activity secreted byPseudomonas aeruginosa. We identified an unreportedP. aeruginosaE3 ligase, which we have termedPseudomonasUb ligase 1 (PUL-1), that resembles none of the other E3 ligases previously established in or outside of the eukaryotic system. Importantly, in an animal model ofP. aeruginosainfection, PUL-1 ligase activity plays an important role in regulating virulence. Thus, our workflow for the functional identification of ubiquitin-targeted effector proteins carries promise for expanding our appreciation of how host ubiquitin regulation contributes to bacterial pathogenesis.
Flexible Adjustment of Oxytocin Neuron Activity in Mother Mice Revealed by Microendoscopy
Authors: Yaguchi Kasane , Miyamichi Kazunari , Tasaka Gen-ichi 
Published: September 2024

AbstractOxytocin (OT) neurons in the hypothalamic paraventricular nucleus (PVH) play an important role in a range of physiological and behavioral processes, including the initiation of milk ejection and the regulation of parental behaviors in mothers. However, their activity patterns at the single-cell level remain poorly understood. Using microendoscopic Ca2+imaging in freely moving mother mice, we demonstrate highly correlated pulsatile activity among individual OT neurons during lactation. The number of OT neurons engaged in the pulsatile activity, along with the characteristics of individual waveforms, was dynamically modulated by lactation and weaning experiences. Notably, only ∼10% of the imaged OT neurons exhibited a significantly elevated response during pup retrieval, a hallmark of maternal behaviors, with a magnitude 18 times smaller than that observed during lactation. Collectively, these findings demonstrate the utility of microendoscopic imaging for PVH OT neurons and highlight the flexible adjustments of their individual activity patterns in freely behaving mother mice.
Global remodeling of ADP-ribosylation by PARP1 suppresses influenza A virus infection
Authors: Zhang Zhenyu , Uribe Isabel , Davis Kaitlin A. , McPherson Robert Lyle , Larson Gloria P , Badiee Mohsen , Tran Vy , Ledwith Mitchell P. , Feltman Elizabeth , Yú Shuǐqìng , Caì Yíngyún , Chang Che-Yuan , Yang Xingyi , Ma Zhuo , Chang Paul , Kuhn Jens H , Leung Anthony K. L. , Mehle Andrew 
Published: September 2024

SUMMARYADP-ribosylation is a highly dynamic and fully reversible post-translational modification performed by poly(ADP-ribose) polymerases (PARPs) that modulates protein function, abundance, localization and turnover. Here we show that influenza A virus infection causes a rapid and dramatic upregulation of global ADP-ribosylation that inhibits viral replication. Mass spectrometry defined for the first time the global ADP-ribosylome during infection, creating an infection-specific profile with almost 4,300 modification sites on ∼1,080 host proteins, as well as over 100 modification sites on viral proteins. Our data indicate that the global increase likely reflects a change in the form of ADP-ribosylation rather than modification of new targets. Functional assays demonstrated that modification of the viral replication machinery antagonizes its activity and further revealed that the anti-viral activity of PARPs and ADP-ribosylation is counteracted by the influenza A virus protein NS1, assigning a new activity to the primary viral antagonist of innate immunity. We identified PARP1 as the enzyme producing the majority of poly(ADP-ribose) present during infection. Influenza A virus replicated faster in cells lacking PARP1, linking PARP1 and ADP-ribosylation to the anti-viral phenotype. Together, these data establish ADP-ribosylation as an anti-viral innate immune-like response to viral infection antagonized by a previously unknown activity of NS1.
A T6SS DNase effector induces nuclear DNA Damage to trigger apoptosis via activation of the cGAS-STING-TNF axis
Authors: Song Li , Xu Lei , Zhang Pengfei , Li Shuying , Zhao Yixin , Shi Zhenkun , Ma Ruiqi , Li Yongdong , Wang Yao , Wei Gehong , Shen Xihui 
Published: September 2024

SUMMARYIn the relentless battle for survival, bacteria have evolved sophisticated weaponry like the Type VI secretion system (T6SS) to not only outcompete rivals but also manipulate host cell processes to their advantage. Apoptosis, a controlled form of programmed cell death without triggering inflammatory responses, is often exploited by pathogens. While many bacterial pathogens are known to induce apoptosis, the role of T6SS effectors in this process remains unexplored. In this study, we discovered thatYersinia pseudotuberculosis(Yptb) utilizes its T6SS to secrete a DNase effector, TkeA, which induces apoptosis in host cells. Mechanistically, the translocation of TkeA into host cells causes nuclear DNA damage, leading to the release of fragmented DNA into the cytoplasm. This, in turn, activates the DNA-sensing cyclic GMP–AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. The activation of the cGAS-STING pathway by TkeA subsequently triggers apoptosis in host cells via extrinsic pathways, with tumor necrosis factor (TNF) signaling playing a critical role. Additionally, TkeA also mediates interbacterial competition, promoting the colonization ofYptbin mice’s gut. Our findings reveal that the T6SS-secreted DNase effector TkeA acts as a trans-kingdom effector, enhancing interbacterial competition and inducing apoptosis in host cells by activating the cGAS-STING-TNF axis. This discovery adds a new dimension to the mechanisms employed by bacterial pathogens to manipulate host cell death pathways by using their secretion systems.GRAPHICAL ABSTRACTHIGHLIGHTS•YptbT6SS secretes a trans-kingdom DNase effector TkeA•TkeA degrades bacterial DNA to mediate interbacterial competition•TkeA causes nuclear DNA damage in host cells to induce apoptosis•TkeA induces apoptosis via the cGAS-STING-TNF axis
Evolution of cooperation in multichannel games on multiplex networks
Authors: Basak Amit , Sengupta Supratim 
Published: September 2024

AbstractHumans navigate diverse social relationships and concurrently interact across multiple social contexts. An individual’s behavior in one context can influence behavior in other contexts. Different payoffs associated with interactions in the different domains have motivated recent studies of the evolution of cooperation through the analysis of multichannel games where each individual is simultaneously engaged in multiple repeated games. However, previous investigations have ignored the potential role of network structure in each domain and the effect of playing against distinct interacting partners in different domains. Multiplex networks provide a useful framework to represent social interactions between the same set of agents across different social contexts. We investigate the role of multiplex network structure and strategy linking in multichannel games on the spread of cooperative behavior in all layers of the multiplex. We find that multiplex structure along with strategy linking enhances the cooperation rate in all layers of the multiplex compared to a well-mixed population, provided the network structure is identical across layers. The effectiveness of strategy linking in enhancing cooperation depends on the degree of similarity of the network structure across the layers and perception errors due to imperfect memory. Higher cooperation rates are achieved when the degree of structural overlap of the different layers is sufficiently large, and the probability of perception error is relatively low. Our work reveals how the social network structure in different layers of a multiplex can affect the spread of cooperation by limiting the ability of individuals to link strategies across different social domains.
Sequestration of oxidative is necessary but not sufficient enough to conclude dopaminergic neuroprotective efficacy of curcumin: Insights from ALSSDrosophilaParkinson’s disease model
Authors: Phom Limamanen , Modi Priyanka , Das Abhik , Yenisetti Sarat C. 
Published: September 2024

AbstractTurmeric is a centuries-old ethnomedicine in Asia. Previously our laboratory demonstrated in the adult life stage-specific (ALSS)Drosophilamodel of Parkinson’s disease (PD) that Curcumin (K)-mediated dopaminergic (DAergic) neuroprotection is absent in the transition stage of adult life during which late-onset neurodegenerative disorders like PD sets-in, suggesting its limitation as a therapeutic agent. The present study demonstrates that K can sequester the enhanced levels of brain oxidative stress (OS) during both adult life phases i.e. health and transition stages but confers neuroprotection only during the health phase. However, literature reviews illustrate that efficacy of supposed therapeutic agents was asserted by their ability to sequester OS in only young PD animal models. In this context, it is important to point out that despite encouraging results in animal models, therapeutic efforts to target the general state of OS failed to retard PD progression. To understand this paradigm, we further investigated ALSS regulation of molecular players in the brain of the ALSS fly PD model and discovered that K-mediated differential modulation of adaptive stress response throughdFOXOcontributes to health phase-specific neuroprotection. These observations suggest that apart from the study of OS markers; it is essential to understand the ALSS regulation of molecular players. The synergistic influence of OS and the ALSS dysfunctional molecular networks could be responsible for the DAergic neurodegeneration in PD. The insights suggest that sequestration of OS by a therapeutic agent is necessary, but inadequate to conclude its neuroprotective efficacy and push it to the next phase of preclinical/clinical evaluation.
Zero-echo time imaging achieves whole brain activity mapping without ventral signal loss in mice
Authors: Imamura Ayako , Araki Rikita , Takahashi Yukari , Miyatake Koichi , Kato Fusao , Honjoh Sakiko , Tsurugizawa Tomokazu 
Published: September 2024

AbstractFunctional MRI (fMRI) is an important tool for investigating functional networks. However, the widely used fMRI with T2*-weighted imaging in rodents has the problem of signal lack in the lateral ventral area of forebrain including the amygdala, which is essential for not only emotion but also noxious pain. Here, we scouted the zero-echo time (ZTE) sequence, which is robust to magnetic susceptibility and motion-derived artifacts, to image activation in the whole brain including the amygdala following the noxious stimulation to the hind paw. ZTE exhibited higher spatial and temporal signal-to-noise ratios than conventional fMRI sequences. Electrical sensory stimulation of the hind paw evoked ZTE signal increase in the primary somatosensory cortex. Formalin injection into the hind paw evoked early and latent change of ZTE signals throughout the whole brain including the subregions of amygdala.Furthermore, resting-state fMRI using ZTE demonstrated the functional connectivity, including that of the amygdala. These results indicate the feasibility of ZTE for whole brain fMRI, including the amygdala and we first show acute and latent activity in different subnuclei of the amygdala complex after nociceptive stimulation.Significance statementFunctional MRI (fMRI) is an important tool for investigating functional networks. However, the widely used fMRI in rodents has the problem of signal lack in the lateral ventral area of forebrain including the amygdala, which is essential for not only emotion but also noxious pain. Here, we used zero-echo time (ZTE) sequence, which was robust to susceptibility artifacts, for functional imaging in the whole brain including amygdala. We demonstrated the feasibility and advantages of using ZTE to investigate neuronal activity in mice. Furthermore, we first showed acute and latent activation in different subnuclei of the amygdala complex as well as other regions related to pain after nociceptive stimulation in mice.
From Genes to Patterns: A Framework for Modeling the Emergence of Embryonic Development from Transcriptional Regulation
Authors: Garcia-Guillen Jimena , El-Sherif Ezzat 
Published: September 2024

AbstractUnderstanding embryonic patterning, the process by which groups of cells are partitioned into distinct identities defined by gene expression, is a central challenge in developmental biology. This complex phenomenon is driven by precise spatial and temporal regulation of gene expression across many cells, resulting in the emergence of highly organized tissue structures. While similar emergent behavior is well understood in other fields, such as statistical mechanics, the regulation of gene expression in development remains less clear, particularly regarding how molecular-level gene interactions lead to the large-scale patterns observed in embryos. In this study, we present a modeling framework that bridges the gap between molecular gene regulation and tissue-level embryonic patterning. Beginning with basic chemical reaction models of transcription at the single-gene level, we progress to model gene regulatory networks (GRNs) that mediate specific cellular functions. We then introduce phenomenological models of pattern formation, including the French Flag and Temporal Patterning/Speed Regulation models, and integrate them with molecular/GRN realizations. To facilitate understanding and application of our models, we accompany our mathematical framework with computer simulations, providing intuitive and simple code for each model. A key feature of our framework is the explicit articulation of underlying assumptions at each level of the model, from transcriptional regulation to tissue patterning. By making these assumptions clear, we provide a foundation for future experimental and theoretical work to critically examine and challenge them, thereby improving the accuracy and relevance of gene regulatory models in developmental biology. As a case study, we explore how different strategies for integrating enhancer activity affect the robustness and evolvability of gene expression patterns in embryonic development. Our simulations suggest that a two-step regulation strategy, enhancer activation followed by competitive integration at the promoter, ensures more standardized integration of new enhancers into developmental GRNs, highlighting the adaptability of eukaryotic transcription. These findings provide new insights into the transcriptional mechanisms underlying embryonic patterning, offering a framework for future experimental and theoretical investigations.
S-band high-gradient low
β
single-periodic magnetically coupled standing-wave accelerating structure for a proton therapy linac
Authors: Qin Wei , Huang Yulu , He Yuan , Dou Weiping , Wang Zhijun , Jin Xiaofeng , Zhang Zhouli , Li Chenxing , Wang Ruoxu , Xin Yuqi , Shi Longbo 
Published: September 2024

S-band high-gradient accelerating structures were proposed to accelerate protons from 30 to 230 MeV for a compact proton therapy linac in Institute of Modern Physics. A backward traveling wave structure and a single-periodic magnetically coupled standing wave structure were designed, and differences between these two structures were analyzed to select a more suitable one for the proton therapy linac. In this paper, a novel single-periodic magnetically coupled standing-wave accelerating structure was studied, with an optimized nose cone that related to a smaller peak surface electric field and higher shunt impedance, with the reduced number of coupling holes and mechanical von Mises stress thus making it possible for higher duty factor and longer rf pulse operation, also with larger coupling holes and improved cell-to-cell coupling thus making this structure suitable for operating in π mode. An 11-cell high-power prototype for β=0.26 particles was developed with an active length of 143 mm. This prototype cavity is supposed to operate at an accelerating gradient of 30  MV/m with 0.1% duty factor, corresponding to a maximum surface electric field of 105  MV/m and a peak rf power of 3.43 MW. Cavity design, optimization, manufacture, rf measurement, and high-power test will be discussed in this paper.

Published by the American Physical Society
2024
Empirical perspective of working capital management practices among large building construction firms in Ghana
Authors: Asare Emmanuel , Owusu-Manu De-Graft , Ayarkwa Joshua , Martek I. , Edwards David John 
Published: September 2024

PurposeThis paper is a response to the failure of construction firms to use sufficient attention to their working capital management (WCM) practices, resulting in operational challenges, and leading to the collapse of firms in most developing countries. Hence, this study aims to explore the empirical perspective of WCM practices among large building construction firms (LBCFs) in Ghana, to help achieve the Sustainable Development Goal 9.Design/methodology/approachThe study collected primary data through structured survey questionnaires from LBCFs in Ghana. The CEOs/Directors, General Managers and Accountant/Finance of LBCFs in Ghana formed the unit of analysis based on a simple random sampling technique. Mean score, standard deviation and one-samplet-test were used to perform the empirical analysis of the study.FindingsAccording to this study's empirical results, LBCFs appear to have effective WCM practices in place. This was evidenced in the surveyed responses which indicate that the sector’s WCM practices sound good based on the mean scores and statistically significant as thet-values > 1.664. Notably, LBCFs in Ghana pay their suppliers early to reduce the fear of adverse effect of late payments on their credit history, making them conservative in their approach toward financial management.Originality/valueThis is a pioneering paper in a developing country like Ghana, highlighting the significance of gaining an in-depth understanding of WCM practices among LBCFs. The findings of this study are expected to provide valuable information to industry players toward ensuring WCM efficiencies and can serve as a solid foundation for further empirical studies.
Trajectory planning and automatic docking of LNG five-axis loading arm
Authors: Jiang FaGuang , Chen Kebing , Chen Yang , Tian Cheng 
Published: September 2024

PurposeIn response to the challenges posed by the conventional manual flange docking method in the LNG (Liquefied Natural Gas) loading process, such as low positioning accuracy, constraints on production efficiency and safety hazards, this study analyzed the LNG five-axis loading arm’s main functions and structural characteristics.Design/methodology/approachAn automated solution for the joints of the LNG loading arm was designed. The forward kinematic model of the LNG loading arm was established using the Denavit–Hartenberg (D-H) parameter method, and its workspace was analyzed. The Newton–Raphson iteration method was employed to solve the inverse kinematics of the LNG loading arm, facilitating trajectory planning. The relationship between the target position and the joint variables was established to verify the stability of the arm’s motion. Flange center identification was achieved using the Hough transform function. Based on the ROS platform, combined with Gazebo and Rviz, an experimental simulation of automatic docking of the LNG loading arm was conducted.FindingsThe docking errors in the XYZ directions were all less than 0.8 mm, meeting the required docking accuracy. Moreover, the motion performance of the loading arm during docking was smooth and free of abrupt changes, validating its capability to accomplish the automatic docking task.Originality/valueThe proposed trajectory planning and automatic docking scheme can be used for the rapid filling of LNG filling arms and LNG tankers to improve the efficiency of LNG transportation. In guiding the docking, the proposed automatic docking scheme is an accurate and efficient way to improve safety.
Asan Cups: navigating blue oceans in menstrual hygiene sustainability
Authors: Tiwari Mitali 
Published: September 2024

Learning outcomes
After completion of the case study, students will be able to understand the format of for-profit social enterprise working for menstrual hygiene sustainability and its contribution toward U.N. Sustainable Development Goals, to appreciate the company’s alignment with the triple bottom line framework, to analyze the blue ocean mechanism that the company has developed to create an impact and to critique the strategies the Asan Cups company could adopt to increase its market share and growth.

Case overview/synopsis
Asan Cups was a for-profit social enterprise founded by Ira Guha in 2021. The company crafted reusable menstrual cups from liquid silicone, sporting a patented design in India, the UK, Europe and the USA. Successfully retailing its products in India, the UK and Europe, Asan Cups operated on a bootstrap model with a compact team of four, led by its visionary founder. From the get-go, the company embraced a compelling 1-for-1 donation initiative. For every cup sold, Asan Cups generously donated another to women who could not afford it. Collaborating with nongovernmental organizations, schools, educational institutions and social workers, the company spearheaded campaigns to heighten menstrual hygiene awareness. This proactive approach aimed to boost the acceptance of menstrual cups among rural women and championed the cause of environmental sustainability. The company did not just stop at providing an eco-friendly alternative. Asan Cups fervently educated the masses on the detrimental environmental impact of traditional disposable period products like sanitary pads and tampons. Fast-forwarding to 2023, Asan Cups had garnered approximately 30,000 users, with the adoption rate steadily climbing. The company strategically used an education-intensive model to foster awareness about period products in collaboration with partners nationwide. However, being a for-profit entity, the founder, Guha, was at a crossroads. Balancing the need for profitability, there was mounting pressure to explore additional revenue streams and expand operations and market reach. The dilemma loomed large: opt for a quicker marketing strategy or stay true to the company’s foundational education-centered approach. This case study delves into the dynamic strategies, impactful operations and growth scenarios Asan Cups navigated since its inception. It examines the pivotal choices faced by the founder and explores potential strategies for sustained growth.

Complexity academic level
This case study can be used at both undergraduate and master’s levels. The case study will be handy for strategic management and business strategy courses and can also be used for social entrepreneurship, marketing and entrepreneurship courses.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 11: Strategy.