bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temperature-Dependent Fold-Switching Mechanism of the Circadian Clock Protein KaiB
Authors: Zhang Ning , Sood Damini , Guo Spencer C. , Chen Nanhao , Antoszewski Adam , Marianchuk Tegan , Chavan Archana , Dey Supratim , Xiao Yunxian , Hong Lu , Peng Xiangda , Baxa Michael , Partch Carrie , Wang Lee-Ping , Sosnick Tobin R. , Dinner Aaron R. , LiWang Andy 
Published: May 2024

ABSTRACTThe oscillator of the cyanobacterial circadian clock relies on the ability of the KaiB protein to switch reversibly between a stable ground-state fold (gsKaiB) and an unstable fold-switched fold (fsKaiB). Rare fold-switching events by KaiB provide a critical delay in the negative feedback loop of this post-translational oscillator. In this study, we experimentally and computationally investigate the temperature dependence of fold switching and its mechanism. We demonstrate that the stability of gsKaiB increases with temperature compared to fsKaiB and that the Q10 value for the gsKaiB → fsKaiB transition is nearly three times smaller than that for the reverse transition. Simulations and native-state hydrogen-deuterium exchange NMR experiments suggest that fold switching can involve both subglobally and near-globally unfolded intermediates. The simulations predict that the transition state for fold switching coincides with isomerization of conserved prolines in the most rapidly exchanging region, and we confirm experimentally that proline isomerization is a rate-limiting step for fold switching. We explore the implications of our results for temperature compensation, a hallmark of circadian clocks, through a kinetic model.
Evolutionary and functional connections between the typhoid toxins encoded byS.Typhi andS. bongori
Authors: Chemello Antonio J. , Fowler Casey C. 
Published: May 2024

ABSTRACTThe virulence properties of numerous important bacterial pathogens have been shaped by the horizontal acquisition of an AB5-type toxin. A major obstacle to the fruitful horizontal transfer of an AB5-type toxin amongst bacteria that infect divergent host species is that these toxins bind specific glycan receptors on target host cells to mediate toxin uptake, and glycosylation patterns vary substantially between different host species. In this study, we explore the evolutionary and functional connections between the related typhoid toxins that are encoded byS. entericaserovar Typhi, a human-adapted pathogen, and byS. bongori, which infects cold-blooded animals. We uncover genetic fingerprints that indicateS. Typhi’s typhoid toxin islet evolved from a larger virulence islet similar toS. bongori’s, and show thatS. Typhi’s glycan-binding PltB subunit is more similar toS. bongoriPltB than it is to many diverse PltB sequence variants found inS. enterica. We further show that, surprisingly,S. Typhi strains that encode theS. bongorityphoid toxin islet intoxicate infected human epithelial cells with substantially greater potency than wild-typeS. Typhi. The results of this study therefore suggest that the unexpected potency of theS. bongorityphoid toxin toward mammalian cells paved the way for sequence variants derived from this species to be acquired by - and effectively integrated into the virulence program of - the human-adapted pathogenS. Typhi.
Norepinephrine Signals Through Astrocytes To Modulate Synapses
Authors: Lefton Katheryn B , Wu Yifan , Yen Allen , Okuda Takao , Zhang Yufen , Dai Yanchao , Walsh Sarah , Manno Rachel , Dougherty Joseph D , Samineni Vijay K , Simpson Paul C , Papouin Thomas 
Published: May 2024

AbstractLocus coeruleus (LC)-derived norepinephrine (NE) drives network and behavioral adaptations to environmental saliencies by reconfiguring circuit connectivity, but the underlying synapse-level mechanisms are elusive. Here, we show that NE remodeling of synaptic function is independent from its binding on neuronal receptors. Instead, astrocytic adrenergic receptors and Ca2+dynamics fully gate the effect of NE on synapses as the astrocyte-specific deletion of adrenergic receptors and three independent astrocyte-silencing approaches all render synapses insensitive to NE. Additionally, we find that NE suppression of synaptic strength results from an ATP-derived and adenosine A1 receptor-mediated control of presynaptic efficacy. An accompanying study from Chen et al. reveals the existence of an analogous pathway in the larval zebrafish and highlights its importance to behavioral state transitions. Together, these findings fuel a new model wherein astrocytes are a core component of neuromodulatory systems and the circuit effector through which norepinephrine produces network and behavioral adaptations, challenging an 80-year-old status quo.
Host-strain compatibility influences transcriptional responses inMycobacterium tuberculosisinfections
Authors: Ruiz-Rodriguez Paula , Caballer-Gual Marta , Santamaria Guillem , Hiza Hellen , Coscolla Mireia 
Published: May 2024

AbstractTuberculosis, caused byMycobacterium tuberculosis, is a leading cause of infectious mortality and affects humans and other mammals. Understanding the drivers of its host-specificity shapes the landscape of infectivity, which could potentially inform strategies for tuberculosis management. We hypothesise that host-strain compatibility influences infection outcome and we aim to reveal bacteria and host specific transcriptional responses duringin vitroinfections.We infected human and bovine cell lines with two human-associatedM. tuberculosisstrains from lineages 5 and 6, as well as two animal-associated strains (Mycobacterium bovisand the Chimpanzee bacillus), and quantified infection ratios, cell death, and transcriptional responses. By integrating those data from different compatibility combinations, we identified global transcription profiles associated with strain-host compatibility.Our results show that the most compatible host-strain combinations had higher infection rates, and different transcriptional patterns than low-compatibility infections. Both hosts had similar transcriptional responses to their most compatible strains, upregulating pathways related with increased cell proliferation. Host proliferation could potentially favour bacterial growth, explaining the success of the strain in its corresponding host. Conversely, both hosts responded to non-associated strains with defence related transcriptional patterns, among other pathways, supporting their lower success in the non-associated host. Finally, we revealed bacteria and host-specific expression patterns in molecules implicated in immune response and inflammation through the eicosanoid pathway.In conclusion, we confirmed that bacteria-host compatibility determines common transcriptional responses, but also specific responses that depend on the infecting strain. This study enhances the understanding of host-specific adaptation mechanisms inM. tuberculosis.
Virus propagation linked to exceedingly rare gene-expression errors
Authors: Luzón-Hidalgo Raquel , d’Agostino Gianluca , Risso Valeria A. , Delgado Asuncion , Ibarra-Molero Beatriz , Campos Luis A. , Requejo-Isidro Jose , Sanchez-Ruiz Jose M. 
Published: May 2024

AbstractViruses are obligate parasites that establish extensive interactions with proteins and other biomolecules of their hosts. About 20% of protein molecules bear phenotypic mutations due to errors during gene expression. Phenotypic mutations are not inherited and are not purged/amplified by natural selection. Therefore, protein variants harboring phenotypic mutations remain at very low levels. Here, we show that proteins at exceedingly low levels may enable virus propagation. Bacteriophage T7 recruits the host thioredoxin as an essential processivity factor for its replisome. Thioredoxin constitutive expression yields 10000-20000 molecules perE. colicell. We inserted early stop codons in the thioredoxin gene and appended to its end the sequence encoding for a photoconvertible fluorescent protein. Virus propagation was not abolished, indicating that some thioredoxin molecules were produced through mistranscription or mistranslation. Single-molecule localization microscopy detected 12±5 molecules per cell when an ochre codon was inserted. This work demonstrates that crucial virus-host biomolecular interactions may need occur only a few times to trigger virus propagation and supports that viruses may exploit the wide diversity of host and viral protein variants arising from gene-expression errors to establish such interactions. Immediate implications of this notion for the mechanisms of cross-species transmission and antibody evasion are discussed.
Astrocytic RIPK3 exerts protective anti-inflammatory activity during viral encephalitis via induction of serpin protease inhibitors
Authors: Lindman Marissa , Estevez Irving , Marmut Eduard , DaPrano Evan M. , Chou Tsui-Wen , Newman Kimberly , Atkins Colm , O’Brown Natasha M. , Daniels Brian P. 
Published: May 2024

AbstractFlaviviruses pose a significant threat to public health due to their ability to infect the central nervous system (CNS) and cause severe neurologic disease. Astrocytes play a crucial role in the pathogenesis of flavivirus encephalitis through their maintenance of blood-brain barrier (BBB) integrity and their modulation of immune cell recruitment and activation within the CNS. We have previously shown that receptor interacting protein kinase-3 (RIPK3) is a central coordinator of neuroinflammation during CNS viral infection, a function that occurs independently of its canonical function in inducing necroptotic cell death. To date, however, roles for necroptosis-independent RIPK3 signaling in astrocytes are poorly understood. Here, we use mouse genetic tools to induce astrocyte-specific deletion, overexpression, and chemogenetic activation of RIPK3 to demonstrate an unexpected anti-inflammatory function for astrocytic RIPK3. RIPK3 activation in astrocytes was required for host survival in multiple models of flavivirus encephalitis, where it restricted neuropathogenesis by limiting immune cell recruitment to the CNS. Transcriptomic analysis revealed that, despite inducing a traditional pro-inflammatory transcriptional program, astrocytic RIPK3 paradoxically promoted neuroprotection through the upregulation of serpins, endogenous protease inhibitors with broad immunomodulatory activity. Notably, intracerebroventricular administration of SerpinA3N in infected mice preserved BBB integrity, reduced leukocyte infiltration, and improved survival outcomes in mice lacking astrocytic RIPK3. These findings highlight a previously unappreciated role for astrocytic RIPK3 in suppressing pathologic neuroinflammation and suggests new therapeutic targets for the treatment of flavivirus encephalitis.
Rab6a enables BICD2/dynein-mediated trafficking of human papillomavirus from thetrans-Golgi network during virus entry
Authors: Choi Jeongjoon , Speckhart Kaitlyn , Tsai Billy , DiMaio Daniel 
Published: May 2024

AbstractRab GTPases control intracellular vesicular transport, including retrograde trafficking of human papillomavirus (HPV) during cell entry, guiding the virus from the endosome to thetrans-Golgi network (TGN), the Golgi apparatus, and eventually the nucleus. Rab proteins that act prior to the arrival of HPV to the TGN have been identified, but Rab proteins operating in later stages of entry remain elusive. Here, we report that knockdown of Rab6a impairs HPV entry by impeding intra-Golgi transport of the incoming virus, resulting in HPV accumulation in the TGN. Rab6a supports HPV trafficking by facilitating the association of HPV with dynein, a motor protein complex, and BICD2, a dynein adaptor. L2 can bind directly to GTP-Rab6ain vitro, and excess of either GTP-Rab6a or GDP-Rab6 inhibits HPV entry, suggesting that cycling between GDP- Rab6 and GTP-Rab6 is critical. Notably, Rab6a is crucial for HPV-BICD2 and HPV-dynein association in the TGN of infected cells, but the HPV-dynein association in the endosome does not require Rab6a. Our findings reveal an important feature of the molecular basis of intra-Golgi trafficking of HPV and identify potential targets for therapeutic approaches to inhibit HPV infection.
The major surface protein of malaria sporozoites is GPI-anchored to the plasma membrane
Authors: Nagar Rupa , Garcia Castillo Stefano S. , Pinzon-Ortiz Maria , Patray Sharon , Coppi Alida , Kanatani Sachie , Moritz Robert L. , Swearingen Kristian E. , Ferguson Michael A. J. , Sinnis Photini 
Published: May 2024

AbstractGlycosylphosphatidylinositol (GPI) anchor protein modification inPlasmodiumspecies is well known and represents the principal form of glycosylation in these organisms. The structure and biosynthesis of GPI anchors ofPlasmodiumspp. has been primarily studied in the asexual blood stage ofP. falciparumand is known to contain the typical conserved GPI structure of EtN-P-Man3GlcN-PI. Here, we have investigated the circumsporozoite protein (CSP) for the presence of a GPI-anchor. CSP is the major surface protein ofPlasmodiumsporozoites, the infective stage of the malaria parasite. While it is widely assumed that CSP is a GPI-anchored cell surface protein, compelling biochemical evidence for this supposition is absent. Here, we employed metabolic labeling and mass-spectrometry based approaches to confirm the presence of a GPI anchor in CSP.Biosynthetic radiolabeling of CSP with [3H]-palmitic acid and [3H]-ethanolamine, with the former being base-labile and therefore ester-linked, provided strong evidence for the presence of a GPI anchor on CSP, but these data alone were not definitive. To provide further evidence, immunoprecipitated CSP was analyzed for presence ofmyo-inositol (a characteristic component of GPI anchor) using strong acid hydrolysis and GC-MS for a highly sensitive and quantitative detection. The single ion monitoring (SIM) method for GC-MS analysis confirmed the presence of themyo-inositol component in CSP. Taken together, these data provide confidence that the long-assumed presence of a GPI anchor on this important parasite protein is correct.
Red Light Mediated Photo-Conversion of Silicon Rhodamines to Oxygen Rhodamines for Single-Molecule Microscopy
Authors: Ritz Jacob M. , Khakimzhan Aset , Dalluge Joseph J. , Noiraeux Vincent , Puchner Elias M. 
Published: May 2024

ABSTRACTThe rhodamine motif has been modified in myriad ways to produce probes with specific fluorescent and chemical properties optimal for a variety of microscopy experiments. Recently, far-red emitting silicon rhodamines have become popular in single-molecule localization microscopy (SMLM), since these dyes are membrane-permeable and can be used alongside red fluorophores for two-color imaging. While this has expanded multi-color SMLM imaging capabilities, we demonstrate that silicon rhodamines can create previously unreported photoproducts with significantly blueshifted emissions, which appear as bright single-molecule crosstalk in the red emission channel. We show that this fluorescence is caused by the replacement of the central silicon group with oxygen after 640 nm illumination, turning far-red silicon rhodamines (JFX650, JF669, etc.) into their red oxygen rhodamine counterparts (JFX554, JF571, etc.). While this blueshifted population can cause artifacts in two-color SMLM data, we demonstrate up to 16-fold reduction in crosstalk using oxygen-scavenging systems. We also leverage this far-red photoconversion to demonstrate UV-free photoactivated localization microscopy (PALM) without the need for additives, and with 5-fold higher efficiency than the Cy5 to Cy3 conversion. Finally, we demonstrate multiplexed pseudo two-color PALM in a single emission channel by separating localizations by their photo-activation wavelengths instead of their emission wavelengths.Abstract Figure
Green supply chain management as a pathway to sustainable operations in the post-COVID-19 era: investigating challenges in the Chinese scenario
Authors: Iqbal Muzaffar , Waqas Muhammad , Ahmad Naveed , Hussain Kramat , Hussain Jafar 
Published: May 2024

PurposeThe disruptive pandemic has badly affected supply chain operations across the globe and implementing green supply chain strategies is challenging for manufacturing firms, especially in emerging countries. Therefore, this study aims to identify the significant challenges hindering the green supply chain as a pathway towards sustainability in the post-COVID-19 era.Design/methodology/approachFuzzy Delphi Methodology (FDM), Interpretive structural modeling (ISM) and MICMAC were applied. FDM was applied to select the most relevant challenges and later ISM and Matrices d'Impacts cross-multiplication appliqúe a classmate MICMAC were used for modeling and classifying critical challenges.FindingsLack of trust between firms and supply chain partners, and difficulty in transforming positive environmental attitudes into action are the significant challenges to implementing green supply chain management. Lack of communication between government and Chinese firms is the least important factor which shows that the government is trying to support firms and reduce the negative effects after the drastic impacts of COVID-19. However, COVID-19 left a draconian effect on organization’s green supply chain and it’s not easy to overcome.Originality/valueNone of the previous studies applied mixed methodologies of FDM, ISM and MICMAC to evaluate Green supply chain as a pathway to sustainable operations in the post-COVID-19 era. Challenging factors of green supply chain operations in COVID-19 are different from earlier studies and contribute to the literature of emerging countries.
A novel fractional multivariate grey prediction model for forecasting hydroelectricity consumption
Authors: Li Ye , Ren Hongtao , Liu Junjuan 
Published: May 2024

PurposeThis study aims to enhance the prediction accuracy of hydroelectricity consumption in China, with a focus on addressing the challenges posed by complex and nonlinear characteristics of the data. A novel grey multivariate prediction model with structural optimization is proposed to overcome the limitations of existing grey forecasting methods.Design/methodology/approachThis paper innovatively introduces fractional order and nonlinear parameter terms to develop a novel fractional multivariate grey prediction model based on the NSGM(1, N) model. The Particle Swarm Optimization algorithm is then utilized to compute the model’s hyperparameters. Subsequently, the proposed model is applied to forecast China’s hydroelectricity consumption and is compared with other models for analysis.FindingsTheoretical derivation results demonstrate that the new model has good compatibility. Empirical results indicate that the FMGM(1, N, a) model outperforms other models in predicting the hydroelectricity consumption of China. This demonstrates the model’s effectiveness in handling complex and nonlinear data, emphasizing its practical applicability.Practical implicationsThis paper introduces a scientific and efficient method for forecasting hydroelectricity consumption in China, particularly when confronted with complexity and nonlinearity. The predicted results can provide a solid support for China’s hydroelectricity resource development scheduling and planning.Originality/valueThe primary contribution of this paper is to propose a novel fractional multivariate grey prediction model that can handle nonlinear and complex series more effectively.
Optimism bias in susceptibility to phishing attacks: an empirical study
Authors: Owen Morné , Flowerday Stephen V. , van der Schyff Karl 
Published: May 2024

Purpose
Researchers looking for ways to change the insecure behaviour that results in phishing have considered multiple possible reasons for such behaviour. Therefore, the purpose of this paper is to understand the role of optimism bias (OB – defined as a cognitive bias), which characterises overly optimistic or unrealistic individuals, to ensure secure behaviour. Research that focused on issues such as personality traits, trust, attitude and Security, Education, Training and Awareness (SETA) was considered.

Design/methodology/approach
This study built on a recontextualized version of the theory of planned behaviour to evaluate the influence that optimism bias has on phishing susceptibility. To model the data, an analysis was performed on 226 survey responses from a South African financial services organisation using partial least squares (PLS) path modelling.

Findings
This study found that overly optimistic employees were inclined to behave insecurely, while factors such as attitude and trust significantly influenced the intention to behave securely.

Practical implications
Our contribution to practice seeks to enhance the effectiveness of SETA by identifying and addressing the optimism bias weakness to deliver a more successful training outcome.

Originality/value
Our study enriches the Information Systems literature by evaluating the effect of a cognitive bias on phishing susceptibility and offers a contextual explanation of the resultant behaviour.
From leadership to allegiance: the interplay of middle leadership, teacher job satisfaction and commitment in schools
Authors: Sothinathan Jayanti S. , Adams Donnie , Mohd Radzi Norfariza 
Published: May 2024

PurposeMiddle leadership is difficult to define and fathom as these roles are fluid, adapting to the context of individual schools. However, little is known about the relationships among middle leadership, teacher commitment and job satisfaction in the field of education. The purpose of this paper is to propose a conceptual framework on the mediating role of teacher job satisfaction in the relationship between middle leadership and teacher commitment in schools based on past research, particularly in the context of schools.Design/methodology/approachA review of literature was undertaken to develop the conceptual framework.FindingsFindings suggested that middle leadership can positively influence teacher commitment via the mediating effect of teacher job satisfaction.Originality/valueThe value of this paper lies in understanding middle leadership as a salient factor in influencing teacher commitment via teacher job satisfaction. This paper’s framework lays a strong foundation for the expansion of the middle leadership knowledge base on middle leadership as well as for future theory development and debate.