bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Throughput Antibody Neutralization Screening in Massively Parallel Droplet Arrays
Authors: Gutierrez-Gonzalez Matias , Fahad Ahmed S. , Delley Cyrille L. , Chung Cheng-Yu , Jin Shuyan , Boyle Nicoleen , de Souza Matheus Oliveira , Pirhanov Azady , Galvez Nicolas M.S. , França Camila T. , Marglous Samantha , Bhagat Evan , Vincent Donovan , Neumeier Daniel , Cao Yi , Doria-Rose Nicole , Reddy Sai T. , Schmidt Aaron G. , Balazs Alejandro B. , Abate Adam R. , DeKosky Brandon J.
Published: February 2025

Neutralizing antibodies provide rapid immune defense against infectious diseases, but are difficult to discover at scale because neutralization assays require live reporter cells and soluble monoclonal antibodies. Here we report Droplet Reporter Cell Testing for Neutralization (DrReCT-Neutralization) to screen antibody gene libraries for their ability to neutralize viral infections. We established the necessary engineered cell lines and validated the DrReCT screening platform using synthetic oligoclonal libraries, followed by an example discovery campaign that demonstrated scalable functional antibody data collection against viral diseases.
Miniaturization of Epileptic Abnormal Electrocorticogram Detector Using 3D Convolutional Neural Network
Authors: Yamaji Moemi , Yamamasu Shinjiro , Hirano Yuto , Hayashida Yuki
Published: February 2025

Epilepsy is a neurological disorder characterized by sudden and recurrent seizures caused by abnormal electrical activity in the brain. Responsive Neurostimulation (RNS) offers a promising treatment option for patients with drug-resistant epilepsy. Responsive Neurostimulation (RNS) is an implantable device that employs a closed-loop system. It continuously monitors brain activity through electro-corticogram (ECoG) recordings. When the system detects seizure activity, it delivers direct electrical stimulation to the brain to suppress the seizure. Seizure detection algorithms require patient-specific optimization, leading to increased interest in deep learning approaches in recent years. While deeper network architectures generally improve detection accuracy, their implementation in implantable devices is constrained by limited hardware resources and the restricted number of electrode channels available for ECoG monitoring. To ensure the practical feasibility of RNS, it is crucial to systematically minimize both the computational costs of patient-specific deep learning models and the number of connected ECoG electrodes. This study systematically reduced the number of electrode channels and computational costs in seizure detection models by analyzing the spatiotemporal kernels learned by the first convolutional layer of a 3D convolutional neural network (3D CNN) trained on 3D ECoG data. This approach capitalizes on the network’s ability to learn spatial relationships between grid electrodes and the temporal dynamics of ECoG signals. The performance comparison between the downsized seizure detection CNN model and the original CNN model revealed that, for at least some patients, it is possible to maintain inference performance while reducing the model size.
A Systematic Review and Meta-Analysis of the Impact of Tumour Mutation Burden on Survival Outcomes in Solid Tumours
Authors: Meng Aijia , Yuile Alexander , Sim Hao-Wen , Thavaneswaran Subotheni , Noor Humaira , Yeung Jacky , Mehta Ashish , Powell Joseph , Zaman Ashraf
Published: February 2025

Background

Tumour mutation burden (TMB) is an emerging pan-cancer biomarker with potential predictive value for immune checkpoint inhibitor (ICI) therapy outcomes. However, its prognostic significance remains inconsistent due to methodological variability and differing cut-off thresholds. This systematic review and meta-analysis evaluated the impact of TMB on overall survival (OS) and progression-free survival (PFS) across solid tumours.

Methods

Following PRISMA 2020 guidelines, we systematically searched PubMed, Scopus, ScienceDirect, and Cochrane databases for studies published between 2010 and 2024. Eligible studies reported hazard ratios (HRs) and 95% confidence intervals (CIs) comparing OS and PFS in high versus low TMB cohorts. Heterogeneity was assessed using the I² statistic, and publication bias via funnel plots and Egger’s test.

Results

A total of 5,278 patients across 28 studies were analysed. High TMB was significantly associated with improved OS and PFS, particularly in non-small cell lung cancer (OS: HR = 0.56), gastrointestinal cancers (OS: HR = 0.36), and advanced/recurrent tumours (OS: HR = 0.52). Survival benefits were most pronounced in ICI-treated patients, especially those receiving combination anti-PD-L1/PD-1 and anti-CTLA4 therapy (OS: HR = 0.47; PFS: HR = 0.50). Ultra-high TMB cases had superior outcomes (OS: HR = 0.44) compared to a universal 10 mut/Mb cut-off (OS: HR = 0.58). Variability in TMB measurement across sequencing platforms highlights the need for standardisation.

Conclusion

High TMB is a strong prognostic and predictive biomarker in ICI-treated cancers, yet methodological inconsistencies hinder clinical implementation. Standardising TMB assessment and refining clinically relevant thresholds are essential for optimising its role in precision oncology.

PROSPERO registration number

The protocol of this systematic review is registered on PROSPERO (CRD42024608809).
Restoration of mitochondrial function to metabolically stressed astrocytes by fusion with mesenchymal stromal cells
Authors: Schneider Remy T. , Rowe Matthew R. , Dawson Rebecca H. , Komrskova Katerina , Neuzil Jiri , Berridge Michael V. , Herst Patries M. , McConnell Melanie J.
Published: February 2025

Mitochondrial networks in eukaryotic cells are dynamic, undergoing fusion, fission, biogenesis and transfer between cells to manage cellular requirements for energy production and biosynthetic components. Mitochondrial transfer has been observed in response to cellular injury and can happen by a variety of mechanisms. To examine whether mitochondria could be restored to injured astrocytes, we established a model of discrete astrocyte-specific, mitochondrial-specific injury in a mixed culture model. Immortalized ρ0astrocytes were generated, then put under lethal metabolic stress by withdrawal of pyruvate and uridine. When cells stressed in this way were grown in the presence of mesenchymal stromal cells, enhanced survival of the ρ0cells was seen, accompanied by the rapid acquisition of an entire mitochondrial networks. Gap-fill ligation and rolling circle amplification for cell-specific mitochondrial genome SNP confirmed that the mitochondrial networks were derived from the mesenchymal stromal donor cells, and both mitochondrial DNA and mitochondrial function were restored to the p0 cells long-term. The presence of two nuclei in the ρ0cells in the early stages of mitochondrial transfer and recovery was observed. This demonstrated that in this instance, the mechanism of mitochondrial rescue was fusion of the ρ0astrocyte and the mesenchymal stromal cell. In support of this, other neural cells were similarly shown to fuse with stressed ρ0astrocytes, suggesting that whole organelles may be donated to restore critical mitochondrial function.
ADrosophilamodel for Costello Syndrome caused by Ras mutation K117R
Authors: Karunaraj Prashath , Cao Emily , Singh Harnoor , Luf Max , Baker Stacey J. , Reddy E Premkumar , Pfleger Cathie M.
Published: February 2025

Germline mutations that increase signaling through the Ras pathway can cause developmental disorders called RASopathies. The RASopathy Costello syndrome has been described to present with hallmarks that include short stature, intellectual disability, cardiac issues, and characteristic facial abnormalities and has been associated with gain-of-function mutations in HRas. The most common HRas mutations in Costello Syndrome occur at G12 and G13, but there are also other rare mutation sites such as K117 including HRasK117R. RasK117Rmutations are also found in colorectal cancer.Drosophilastudies modeling gain-of-function in Ras primarily utilize the common cancer-associated mutation G12V, and previousDrosophilaRASopathy models assessing Ras gain-of-function mutations have used human sequences for KRas G12D and HRas G12S. To augment these studies, we characterized the phenotype of engineering the rare gain-of-function mutation K117R in theDrosophilaRas sequence. We report here that constitutive low-level expression of RasK117Rincreased lethality and reduced body size while also causing rough eye and ectopic wing vein phenotypes in those flies that survived to adulthood. Ras pathway inhibitors Trametinib and Rigosertib suppressed the lethality but not the reduced size phenotypes. Trametinib strongly suppressed the K117R wing vein phenotype whereas Rigosertib had only subtle effects. Trametinib is a direct MEK inhibitor. Rigosertib has been reported to have strong effects on PI3K signaling and to indirectly inhibit the Raf-ERK branch. Therefore, this data is consistent with an interpretation that some lethality in the fly RasK117Rmodel depends on elevated signaling through the Raf-ERK branch and potentially some lethality depends on the PI3K branch. In contrast, the lack of effects on the reduced size phenotypes would be consistent with small stature resulting from Raf- and PI3K-independent processes. We propose that this model can be useful for future mechanistic analysis and pharmacological screening and evaluation.
CTCF directly binds G-quadruplex structures to regulate genome topology and gene expression
Authors: Castruita Daniela Samaniego , Han Isabella , Morgan Roxroy C , Carpenter Samantha , Williams Bryce , Chakraborty Abhijit , Radhakrishnan Ishwar , Ay Ferhat , Myers Samuel A , Rao Anjana , Shukla Vipul
Published: February 2025

DNA G-quadruplexes (G4s) are non-B form secondary DNA structures that are highly conserved across evolution. G4 structures occupy key regulatory sites in the mammalian genomes and are implicated in several cellular processes. However, the mechanisms by which G4s contribute to distinct facets of genome function are not well understood. Here, we conduct a proteomics screen with G4s of diverse topologies to uncover novel G4 binding activities in genomic regulators of nucleosome remodeling, paraspeckle assembly, RNA splicing, transcriptional elongation, and 3D genome organization. Among the most prominent hits, we identify the genomic architectural protein, CTCF, as one of the strongest G4 binders. Building on this discovery, we perform extensive biochemical validation of CTCF-G4 interaction and identify CTCF mutants, with pronounced affinity for G4s over its consensus DNA motif. By implementing well-established approaches and developing new G4 mapping tools, we define a comprehensive catalog of genomic G4s and investigate their association with CTCF binding. Using genetic reconstitution of mouse embryonic stem cells with a G4-specific CTCF mutant, we ascribe genomic functions to CTCF-G4 interactions in regulation of CTCF occupancy, chromatin looping and gene expression. Interestingly, our studies reveal a subset of G4-linked chromatin loop anchors that form persistent loops which are retained even upon CTCF depletion. Collectively, our work establishes the G4 binding activity of CTCF and provides new insights into the functional significance of G4 structures.
Intratumoral gene delivery of 4-1BBL boosts IL-12-triggered anti-glioblastoma immunity
Authors: Lunavat Taral R. , Nieland Lisa , Looij Sanne M. van de , Reus Alexandra J.E.M. de , Couturier Charles P. , Farran Chadi A. El , Miller Tyler E. , Lill Julia K. , Schübel Maryam , Xiao Tianhe , Ianni Emilio Di , Woods Elliot C. , Sun Yi , Rufino-Ramos David , Solinge Thomas S. van , Mahjoum Shadi , Grandell Emily , Li Mao , Mangena Vamsi , Dunn Gavin P. , Jenkins Russell W. , Mempel Thorsten R. , Breakefield Xandra O. , Breyne Koen
Published: February 2025

The standard of care in high-grade gliomas has remained unchanged in the past 20 years. Efforts to replicate effective immunotherapies in non-cranial tumors have led to only modest therapeutical improvements in glioblastoma (GB).

Here, we demonstrate that intratumoral administration of recombinant interleukin-12 (rIL-12) promotes local cytotoxic CD8POST cell accumulation and conversion into an effector-like state, resulting in a dose-dependent survival benefit in preclinical GB mouse models. This tumor-reactive CD8 T cell response is further supported by intratumoral rIL-12-sensing dendritic cells (DCs) and is accompanied by the co-stimulatory receptor 4-1BB expression on both cell types. Given that DCs and CD8POST cells are functionally suppressed in the tumor microenvironments ofde novoand recurrent glioma patients, we tested whether anti-tumor response at the rIL-12-inflamed tumor site could be enhanced with 4-1BBL, the ligand of 4-1BB. 4-1BBL was delivered using an adeno-associated virus (AAV) vector targeting GFAP-expressing cells and resulted in prolonged survival of rIL-12 treated GB-bearing mice.

This study establishes that tumor antigen-specific CD8 T cell activity can be directed using an AAV-vector-mediated gene therapy approach, effectively enhancing anti-GB immunity.
APOE4exacerbates glucocorticoid stress hormone-induced tau pathology via mitochondrial dysfunction
Authors: Yu Qing , Du Fang , Goodman Jeffrey , Waites Clarissa L.
Published: February 2025

APOE4is the leading genetic risk factor for Alzheimer’s disease, and chronic stress is a leading environmental risk factor. Studies suggest thatAPOE4confers vulnerability to the behavioral and neuropathological effects of chronic stress, representing a potential mechanism by which this genetic variant accelerates Alzheimer’s onset and progression. Whether and howAPOE4-mediated stress vulnerability manifests in neurons of the hippocampus, a brain region particularly susceptible to stress and Alzheimer’s pathology, remains unexplored.

Using a combination ofin vivoandin vitroexperiments in humanizedAPOE4andAPOE3knockin mice and primary hippocampal neurons from these animals, we investigate whether and howAPOE4confers sensitivity to glucocorticoids, the main stress hormones.

We find that a major hallmark of stress/glucocorticoid-induced brain damage, tau pathology (i.e., tau accumulation, hyperphosphorylation, and spreading) is exacerbated inAPOE4versusAPOE3mice. Moreover,APOE4animals exhibit underlying mitochondrial dysfunction and enhanced glucocorticoid receptor activation in the hippocampus, factors that likely contribute to tau pathogenesis in both the presence and absence of stress/glucocorticoids. Supporting this concept, we show that opening of the mitochondrial permeability transition pore drives mitochondrial dysfunction and tau pathology inAPOE4mice, and that pharmacological inhibition of pore opening is protective against ApoE4-mediated mitochondrial damage, tau phosphorylation and spreading, and downstream hippocampal synapse loss. These findings shed light on the mechanisms of stress vulnerability inAPOE4carriers and identify the mitochondrial permeability transition pore as a potential therapeutic target for ameliorating Alzheimer’s pathogenesis in this population.
Developmental Variations in Recurrent Spatiotemporal Brain Propagations from Childhood to Adulthood
Authors: Byeon Kyoungseob , Park Hyunjin , Park Shinwon , Cluce Jon , Mehta Kahini , Cieslak Matthew , Cui Zaixu , Hong Seok-Jun , Chang Catie , Smallwood Jonathan , Satterthwaite Theodore D. , Milham Michael P. , Xu Ting
Published: February 2025

The brain undergoes profound structural and functional transformations from childhood to adolescence. Convergent evidence suggests that neurodevelopment proceeds in a hierarchical manner, characterized by heterogeneous maturation patterns across brain regions and networks. However, the maturation of the intrinsic spatiotemporal propagations of brain activity remains largely unexplored. This study aims to bridge this gap by delineating spatiotemporal propagations from childhood to early adulthood. By leveraging a recently developed approach that captures time-lag dynamic propagations, we characterized intrinsic dynamic propagations along three axes: sensory-association (S-A), 'task-positive' to default networks (TP-D), and somatomotor-visual (SM-V) networks, which progress towards adult-like brain dynamics from childhood to early adulthood. Importantly, we demonstrated that as participants mature, there is a prolonged occurrence of the S-A and TP-D propagation states, indicating that they spend more time in these states. Conversely, the prevalence of SM-V propagation states declines during development. Notably, top-down propagations along the S-A axis exhibited an age-dependent increase in occurrence, serving as a superior predictor of cognitive scores compared to bottom-up S-A propagation. These findings were replicated across two independent cohorts (N = 677 in total), emphasizing the robustness and generalizability of these findings. Our results provide new insights into the emergence of adult-like functional dynamics during youth and their role in supporting cognition.
Directed evolution of a SelB variant that does not require a SECIS element for function
Authors: Ishida Satoshi , Gundlach Arno , Kosonocky Clayton W. , Ellington Andrew D.
Published: February 2025

In bacteria the incorporation of selenocysteine is achieved through the interaction of the selenocysteine specific elongation factor (SelB) with selenocysteine-charged tRNASecand a selenocysteine insertion sequence (SECIS) element adjacent to an opal stop codon in a mRNA. The more generalized, SECIS-independent incorporation of selenocysteine is of interest because of the high nucleophilicity of selenium and the greater durability of diselenide bonds. It is likely that during the course of evolution selenocysteine insertion originally arose without the presence of a SECIS element, relying only on SelB. Herein we undertake experiments to evolve an ancestral version of SelB that is SECIS-independent and show that not only can this protein (SelB-v2) generally incorporate selenocysteine across from stop codons, but also that the new, orthogonal translation factor can be repurposed to other amino acids, such as serine. Given the delicate energetic balancing act already performed by EF-Tu, this achievement raises the possibility that greatly expanded genetic codes that relied in part on SelB-based loading can now be contrived.
Mac/Lac-tosylceramide regulates intestinal homeostasis and secretory cell fate commitment by facilitating Notch signaling
Authors: Tang Kebei , Li Xuewen , Hu Jiulong , Shi Jingyuan , Li Yumei , Chen Yansu , Yin Chang , Wang Fengchao , Xi Rongwen
Published: February 2025

Cell-to-cell communication via Delta-Notch signaling is widely used in various tissues and organs to regulate development and patterning; however, the mechanisms regulating Notch signaling for precise cell fate decisions remain poorly understood. Similar to mammals, the intestinal stem cells (ISCs) in the adultDrosophilamidgut generate both absorptive and secretory cell progeny, guided by differential levels of Notch activation. Here we performed a forward genetic screen inDrosophilaand identified glucosylceramide synthase (GlcT), a rate-limiting enzyme for glycosphingolipid (GSL) production, whose mutation causes the development of secretory cell tumors. Genetic analysis of the GSL synthesis pathway, combined with metabolite rescue experiments, revealed that the tumor formation is linked to a deficiency in Mactosylceramide/Lactosylceramide. This deficiency impaired the endocytic recycling of the Delta, subsequently reducing Notch signaling activation. Conditional knockout ofUGCG, the mammalian ortholog ofGlcT, in mouse small intestine caused an excessive differentiation of goblet cells, phenotypes similar to these caused by Notch inhibition. Our study suggests an evolutionarily conserved role for a specific GSL metabolite in modulating Notch signaling during stem cell fate decisions and provides a molecular connection between ceramide metabolism and Notch signaling in regulating tissue homeostasis and tumor formation.
A kinetics-based model of hematopoiesis reveals extrinsic regulation of skewed lineage output from stem cells
Authors: Rodriguez-Correa Esther , Gruenschlaeger Florian , Nizharadze Tamar , Anstee Natasha , Al-Sabah Jude , Kumpost Vojtech , Sedlmeier Anastasia , Li Congxin , Ball Melanie , Fotopoulou Foteini , Jayarajan Jeyan , Ghezzi Ian , Knoch Julia , Druce Megan , Aurich Theo , Buechler-Schaeff Marleen , Lux Susanne , Hernandez-Malmierca Pablo , Graesel Julius , Vonficht Dominik , Mathioudaki Anna , Zaugg Judith B , Mikut Ralf , Trumpp Andreas , Hoefer Thomas , Huebschmann Daniel , Haas Simon , Milsom Michael D
Published: February 2025

Residing at the top of the hematopoietic hierarchy, long-term hematopoietic stem cells (HSCs) are capable of self-renewal and sustained blood cell regeneration. Over the past decades, single-cell and clonal analyses have revealed substantial functional and molecular heterogeneity within this compartment, challenging the notion that self-renewal is inherently tied to balanced, multi-lineage blood production. However, a cohesive model that explains the relationships among these diverse HSC states remains elusive. Here, we combined single-cell transplantations of over 1,000 highly purified murine long-term HSCs with in-depth phenotyping of their clonal progeny to achieve a detailed, time-resolved understanding of heterogeneous reconstitution outcomes. We identified reconstitution kinetics as an overall unifying metric of HSC functional potency, with the most potent HSCs displaying the greatest delay in hematopoietic reconstitution. Importantly, a progressive acceleration in reconstitution kinetics was also associated with a gradual shift in mature cell production from platelet and erythro-myeloid bias to balanced, and eventually lymphoid bias. Serial single-cell transplantations of HSCs revealed a unidirectional acceleration in reconstitution kinetics accompanied by a gradual decline in functional potency of daughter HSCs, aligning diverse phenotypes along a linear hierarchical trajectory. Mathematical modeling, together with experimental modulation of lineage-biased blood production, demonstrated that apparent lineage biases actually arise from cell-extrinsic feedback regulation and clonal competition between slow- and fast-engrafting clones to occupy the limited compartment sizes of mature lineages. Our study reconciles multiple layers of HSC heterogeneity into a unifying framework, prompting a reevaluation of the meaning of lineage biases in both normal and diseased hematopoiesis, with broad implications for other regenerating tissues during development, homeostasis, and repair.
rTCT: Rodent Triangle Completion Task to facilitate translational study of path integration
Authors: Duncan Stephen , Rehman Sulaiman , Sagen Vladislava , Choi Irene , Lawrence Sami , Kalani Om , Gold Lisette , Goldman Lillian , Ramlo Sophia , Stickel Kylene , Layfield Dylan , Wolbers Thomas , Tiganj Zoran , Newman Ehren L.
Published: February 2025

Path integration is navigation in the absence of environmental landmarks and is a primary cognitive mechanism underlying spatial memory. Path integration performance is primarily assessed in humans using the Triangle Completion Task (TCT). In humans, TCT has shown promise for the early diagnosis of Alzheimer’s disease. In rodents, however, path integration is assessed using a wide variety of tasks but none of which currently provide a homologue for the TCT. As rodents are routinely used as preclinical models, homologous path integration tasks that result in comparable performance metrics between species are important. In the present study we developed and tested a novel rodent version of the triangle completion task to enhance cross species comparability of path integration performance. Rats were able to comprehend and perform the task. A group of Alzheimer’s disease model rats (TgF344-AD) exhibited similar path integration performance to their wild-type littermates; however, analysis of behavioural structure suggests use of differing behavioural strategies. This work establishes a novel rodent homologue of the triangle completion task, facilitating enhanced reverse translational study of human path integration.
A Meta-analysis of Perceptual Pseudoneglect reveals the Functional Anatomy of Perceptual Judgements
Authors: Abdul-Nabi Mura , Niemeier Matthias
Published: February 2025

Major evidence for a right-hemisphere dominance of the brain in spatial and/or attentional tasks comes from lesion studies in patients with spatial neglect. However, the neuroanatomy of the different forms of neglect remains a matter of debate, and it remains unclear how dysfunctions in neglect relate to intact processes. In the healthy brain, perceptual pseudoneglect is the equivalent of neglect as observed in paradigms such as the line bisection task. Therefore, the current study investigated the intact functional anatomy of perceptual pseudoneglect using a meta-analysis to compensate for some of the limitations of individual imaging studies. We collated the data from 24 articles that tested 952 participants with a range of paradigms (landmark task, line bisection, grating-scales task, and number line task) obtaining 337 foci. Using Activation Likelihood Estimation (ALE) we identified a right-hemisphere biased network of cortical areas, including superior and intraparietal regions, the intraoccipital sulcus together with other occipital regions, as well as inferior frontal areas that were associated with perceptual pseudoneglect in partial agreement with lesion studies in patients with neglect. The present results are consistent with a framework of neural computations that explains the neural and behavioural asymmetries of perceptual pseudoneglect as due the need for to an integrated representation of spatial information during perceptual judgments.
Spatial variation in benthic community composition on a minimally disturbed coral reef in the years following a prolonged marine heatwave
Authors: Hansen Rebecca L. G. , Halford Andrew , Maucieri Dominique G. , Baum Julia K.
Published: February 2025

With the increased frequency of marine heatwaves and related coral mass mortality events, it is imperative that we improve our understanding of coral reef recovery processes including how benthic community compositions can change over time. Coral reef benthic communities are influenced by many abiotic factors, but on most reefs local anthropogenic disturbances overshadow these factors thus obscuring their influence. Here, we leverage a dataset from a coral reef with very minimal local anthropogenic disturbance - the uninhabited southern coast of the world's largest atoll (Kiritimati) - to assess spatial variation in benthic community composition three years after the mass coral mortality event driven by the 2015-2016 El Niño. Across forereef sites ranging from 7 to 22 m, scleractinian coral cover remained very low (6.9 +/- 0.4 % SE) while soft coral cover was < 1%. Coral cover was highest at deep sites (18-22 m compared to sites at 7-10 m depth) and exposed locations, where stress-tolerant corals likely made up a larger proportion of the coral community before the mass mortality event. Higher cover of crustose coralline algae at shallow exposed sites, fleshy macroalgae at deep sites, and turf algae at exposed locations were consistent with taxa-specific preferences for light, wave action, and sedimentation. The abundances of the most common genera of juvenile coral (Acropora and Pocillopora) were still low (< 1 juvenile colony per genus per site) and varied only with depth. These findings demonstrate how variation in pre-mortality coral composition can lead to differences in post-mortality benthic communities on low disturbance coral reefs.
RAB18 Orchestrates Signaling Protein Ciliary Homeostasis by Facilitating BBSome Diffusion through the Transition Zone for Ciliary Entry
Authors: Sun Wei-Yue , Zhang Jingchao , Wei Yan , Zhao Linda S. , Fan Zhen-Chuan
Published: February 2025

The BBSome acts as an intraflagellar transport (IFT) cargo adaptor that connects transmembrane and membrane-anchored signaling proteins to the process of IFT within cilia. This function is critical for ciliary homeostasis maintenance of signaling proteins, allowing for successfully sensing and transducing extracellular stimuli inside the cell. It is established that, upon reaching the proximal ciliary region just above the transition zone (TZ), a diffusion barrier, via retrograde IFT, the BBSome, carrying signaling proteins, disengages from IFT and diffuses through the TZ for ciliary retrieval. This TZ passage event is promoted by the Arf-like 3 GTPase, which utilizes the BBSome autonomously of IFT association as its major effector. While it is known that the intact BBSome is recruited to the basal bodies before entering cilia, the precise mechanism by which it crosses the TZ to access cilia remains elusive. In our study onChlamydomonas reinhardtii, we disclose that the Ras-associated binding (Rab) GTPase RAB18 is concentrated in a basal body region that overlaps with the BBSome. Positioned at this location, RAB18 in a GTP-bound state (RAB18-GTP) is anchored to the membrane, allowing it to diffuse into cilia. Throughout this process, the BBSome functions as a RAB18 effector, binding to RAB18-GTP and subsequently being recruited to diffuse through the TZ for ciliary entry in an IFT-independent manner. This collaboration between the BBSome and RAB18 is pivotal in maintaining the signaling protein phospholipase D ciliary homeostasis, providing a precise mechanistic understanding of the inward BBSome TZ passage essential for proper ciliary signaling.

Significance statement

Although certain ciliary signaling proteins cross the transition zone (TZ) for ciliary removal via the RABL2-ARL3 module-mediated outward BBSome TZ diffusion pathway, how the BBSome passes the TZ for ciliary entry remains unclear. Here, we show that RAB18, in its GTP-bound state, anchors to the membrane at the basal bodies. As a RAB18 effector, the BBSome is recruited to cross the TZ for ciliary entry via lateral transport between plasma and ciliary membranes. Once inside cilia, the BBSome integrates into anterograde IFT trains and subsequently functions as a phospholipase D (PLD) adaptor, ensuring PLD removal from cilia. This study highlights RAB18’s pivotal role in facilitating BBSome entry into cilia, unveiling a regulatory mechanism crucial for maintaining ciliary signaling protein homeostasis.
Remote Cortical Network for Frontal Cognitive Symptoms derived from Tau Accumulation in Progressive Supranuclear Palsy
Authors: Hori Yuki , Endo Hironobu , Tagai Kenji , Kataoka Yuko , Goto Ryoji , Kurose Shin , Momota Yuki , Kokubo Naomi , Seki Chie , Moriguchi Sho , Shimada Hitoshi , Shinotoh Hitoshi , Tokuda Takahiko , Takahata Keisuke , Minamimoto Takafumi , Higuchi Makoto , Hirabayashi Toshiyuki
Published: February 2025

Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterized by movement impairments and frontal cognitive dysfunctions. While motor symptoms are linked with subcortical tau deposits, mechanisms underlying the frontal cognitive symptoms remain unclear due to limited tau accumulation in the frontal cortex and heterogeneous tau distribution. Here, we combined high-contrast tau PET with normative connectome to identify a common network extended from tau deposits underlying the frontal cognitive symptoms in PSP. Regions with tau deposition were connected to a common cortical network that was not detectable through atrophy-based analyses. This network was primarily overlapped with canonical action-mode and frontoparietal networks. While the degree of subcortical tau deposition or atrophy correlated with motor symptoms, only connectivity between tau deposition sites and the derived cortical network explained the frontal cognitive deficits. These findings propose network mechanisms underlying frontal cognitive impairments in PSP, emphasizing the role for remote effects of pathological tau deposits.
Integration of conditioned threat with pre-existing memories
Authors: de Vries Olivier T. , Kindt Merel , van Ast Vanessa A.
Published: February 2025

How does negative affect spread through existing memories? Whereas many studies have investigated generalization of learned threat responses across perceptual and semantic dimensions, little attention has been given to the possibility that Pavlovian threat responses may spread beyond what is directly learned to previously encoded memories that overlap in content. Here, we increased the demand on associative memory in a modified sensory preconditioning task to investigate this. First, participants encoded 40 unique episodes, each consisting of two neutral stimuli. On the following day, one of each pair was newly associated with either an aversive or a neutral stimulus. Another day later, both stimuli of the original memories were found to trigger enhanced pupil dilation if one was indirectly linked to an aversive stimulus. This effect was independent of whether the associations encoded on day 1 were accurately retained on the day of testing, and confined to trials on which the indirectly associated stimulus was consciously brought to mind, suggesting the formation of a link that directly connects preconditioned stimuli to subsequently learned aversive outcomes. The present study demonstrates that the human defensive system is remarkably adept at quickly anticipating threat based on information acquired over separate events, and gives a first glimpse into the associative structures that enable this ability.
Optically pumped vector magnetometer using a strong bias magnetic field
Authors: Schönau Thomas , Scholtes Theo , Wittkämper Florian , Sekels Alexander , Hiebel Stefan , Oelsner Gregor , Stolz Ronny
Published: February 2025

We present an approach allowing an optically pumped magnetometer (OPM) to be operated within the Earth’s magnetic field as a vector magnetometer, the sensitive axis of which can be freely defined. This approach enables the measurement of any vector component of the Earth’s magnetic field with the same sensitivity. The OPM is realized by a microfabricated cesium-vapor cell with nitrogen buffer gas, which is immersed in a constant homogeneous bias field of approximately 730μT. Since this bias field is about one order of magnitude stronger than the Earth’s magnetic field, it defines the sensitive axis of the OPM. The bias field is generated by solid-state magnets and has been designed to exhibit a very low relative inhomogeneity (<±10−4 in relative units) within the vapor-cell dimensions as well as a point of vanishing temperature dependence at around 40∘C. The OPM utilizes the light-narrowing effect, which enables effective suppression of spin-exchange relaxation even in such a large magnetic field amplitude. Based on this implementation, we demonstrate a white-noise floor of below 60fT/Hz in the frequency interval between 100Hz and 600 Hz and a 3-dB sensor bandwidth of >5kHz. Our approach enables unshielded ultrasensitive vectorial measurement capabilities that are relevant in many important applications.

Published by the American Physical Society
2025
Gribov copies in the quark propagator
Authors: Kalusche Gerhard , Lawlor Dale , Skullerud Jon-Ivar
Published: February 2025

We study the impact of Gribov copies on the quark propagator in lattice 2-color quantum chromodynamics (QCD). We find that the Gribov noise is comparable to the gauge noise for smaller volumes but becomes less significant for larger spatial volumes. The Gribov noise in the quark propagator is found to be comparable to, but smaller than in the gluon propagator on the same ensembles. No correlation is found between the values of either of the quark propagator form factors and the value of the gauge fixing functional, nor between the two form factors.

Published by the American Physical Society
2025
Hilbert space of quantum field theory in de Sitter spacetime
Authors: Penedones Joao , Salehi Vaziri Kamran , Sun Zimo
Published: February 2025

We study the decomposition of the Hilbert space of quantum field theory in (d+1)-dimensional de Sitter spacetime into unitary irreducible representations (UIRs) of its isometry group SO(1,d+1). First, we consider multiparticle states in free theories starting from the tensor product of single-particle UIRs. Second, we study conformal multiplets of a bulk conformal field theory with symmetry group SO(2,d+1). Our main tools are the Harish-Chandra characters and the numerical diagonalization of the (truncated) quadratic Casimir of SO(1,d+1). We introduce a continuous density that encodes the spectrum of irreducible representations contained in a reducible one of SO(1,d+1). Our results are complete for d=1 and d=2. In higher dimensions, we rederive and extend several results previously known in the literature. Our work provides the foundation for future nonperturbative bootstrap studies of quantum field theory in de Sitter spacetime.

Published by the American Physical Society
2025
In situ
dynamic four-dimensional strong-field ionization tomography
Authors: Shlomo Noam , Frumker Eugene
Published: February 2025

We present an dynamic four-dimensional (4D=3D space + 1D time) laser induced strong field ionization tomography technique, particularly suited for probing far-from-equilibrium systems, such as supersonic and hypersonic pulsed gas jets. By employing a femtosecond laser, temporal resolution is primarily limited by electronic jitter, typically to a few tens of picoseconds. Our proof-of-principle experiment revealed an intriguing phenomenon: a “squeezing” of the gas pulse as it propagates downstream, manifesting as a shortening of the normalized temporal profile of the gas pulse density along the propagation axis, while simultaneously expanding transversely.

Published by the American Physical Society
2025
Scalable Networking of Neutral-Atom Qubits: Nanofiber-Based Approach for Multiprocessor Fault-Tolerant Quantum Computers
Authors: Sunami Shinichi , Tamiya Shiro , Inoue Ryotaro , Yamasaki Hayata , Goban Akihisa
Published: February 2025

Neutral atoms are among the leading platforms toward realizing fault-tolerant quantum computation (FTQC). However, scaling up a single neutral-atom device beyond 104 atoms to meet the demands of FTQC for practical applications remains a challenge. To overcome this challenge, we clarify the criteria and technological requirements for further scaling based on multiple neutral atom quantum processing units (QPUs) connected through photonic networking links. Our quantitative analysis shows that nanofiber optical cavities have the potential as an efficient atom-photon interface to enable fast entanglement generation between atoms in distinct neutral-atom modules, allowing multiple neutral-atom QPUs to operate cooperatively without sacrificing computational speed. Using state-of-the-art millimeter-scale nanofiber cavities with the finesse of thousands, over a hundred atoms can be coupled to the cavity mode with an optical tweezer array, with expected single-atom cooperativity exceeding 100 for telecom-band transition of ytterbium atoms. This enables efficient time-multiplexed entanglement generation with a predicted Bell-pair generation rate of 105s−1 while maintaining a small footprint for channel multiplexing. These proposals and results indicate a promising pathway for building large-scale multiprocessor fault-tolerant quantum computers using neutral atoms, nanofiber optical cavities, and fiber-optic networks.

Published by the American Physical Society
2025
New online beam intensity synchronous monitoring system in scanning transmission X-ray microscopy
Authors: Jiao Yuchen , Zhang Xiangzhi , Xu Zijian , Yao Zhen , Sun Tianxiao , Zhang Yufei , Zhao Bo , Guo Zhi , Wang Yong , Zhen Xiangjun , Liu Haigang , Liang Shasha , Li Haitao , Zhao Xuanyu , He Jian , Tai Renzhong
Published: February 2025

The scanning transmission X-ray microscopy (STXM) platform based on synchrotron radiation has achieved nanoscale imaging with chemical sensitivity using spectro-microscopy techniques. However, the quality of STXM imaging is affected by the stability of the beam intensity. The top-up operation mode of synchrotrons to maintain a constant electron beam intensity introduces periodic fluctuations in the X-ray beam intensity, leading to notable imaging noise that decreases both contrast and precision. To address this issue, a high-speed real-time beam intensity monitoring system was designed and implemented at the BL08U1A beamline of the Shanghai Synchrotron Radiation Facility. This system utilizes an yttrium–aluminium–garnet crystal along with dual detectors having an acquisition frequency of up to 1 MHz and a synchronization error of less than 20 ns between them. This system can precisely and synchronously monitor the X-ray beam intensity variations which are used to remove noise due to electron injection from STXM images, thereby markedly improving the quality of STXM imaging.
Stablecoins and emerging market currencies: a time-varying analysis
Authors: Napari Ayuba , Khan Asad Ul Islam , Kaplan Muhittin , Vergil Hasan
Published: February 2025

Purpose

Owing to the growing evidence of crypto asset connectedness and correlation with traditional financial assets, this study sought to determine if there is a time-varying correlation and/or connectedness between the stablecoin market and the currencies of emerging market and developing economies (EMDEs) with significant cryptocurrency penetration.

Design/methodology/approach

This study uses a probabilistic principal component analysis (PPCA) to create stablecoin and EMDEs currency returns and volatility indices for EMDEs with significant cryptocurrency penetration. We then employ a time-varying correlation and time-varying parameter vector autoregressive (TVP-VAR) connectedness measures to document the time-dependent correlation and connectedness between the EMDE currencies and the stablecoin market.

Findings

The result points to a spillover of return shocks from the EMDE currencies to the stablecoin market prior to and after the COVID-19 pandemic. This is indicative of a flight-to-safety role of stablecoins for EMDE currencies. This calls for increased attention to the stablecoin market by money market investors and monetary authorities.

Originality/value

The paper contributes to the growing cryptocurrency and finance literature by empirically examining the level of connectedness between stablecoins and emerging market currencies. Knowing the relationship (correlation) and shock spillover (connectedness) between the stablecoins and the EMDE currencies will be valuable to currency investors’ diversification and hedging strategies, and to macroeconomic policymakers in designing and implementing regulation.
Environmental sustainability and the happy-productive worker: examining the impact on employee well-being and work performance in educational institutions
Authors: Sheeran Zane , Sutton Anna , Cooper-Thomas Helena Dorothy
Published: February 2025

Purpose

The happy-productive worker hypothesis posits that employee well-being is an important factor in work performance. Educational institutions around the world are facing both internal and external pressures to integrate sustainability into their practices, with the goal of protecting the planet and ultimately boosting profits. This paper explores the potential wider benefits of sustainability, including its relationship with employee well-being and performance, by investigating the influence of organisational sustainability on the happy-productive worker hypothesis.

Design/methodology/approach

Educational institution employees from the UAE and USA (n = 199; 66.3% teachers) completed an online questionnaire measuring their well-being, perceptions of their organisations’ environmental sustainability and three self-reported job performance measures (task performance, contextual performance and counter-productive workplace behaviours). Regression and mediation analyses were conducted to test hypothesised relationships.

Findings

Both well-being and sustainability were positively associated with work performance. Furthermore, sustainability accounted for additional variance in performance beyond that accounted for by well-being. Sustainability partially mediated the relationship between well-being and performance, providing evidence of the importance of sustainability in the workplace.

Originality/value

This study contributes to an emerging field by investigating the relationship between an organisation’s sustainability and benefits of this for employees in terms of well-being as well as work performance. The findings provide further support for the happy-productive worker hypothesis and also the first evidence that educational institutions’ sustainability can mediate this relationship.
Tyrannical leadership and knowledge hiding: the mediating role of psychological distress and moderating role of psychological resilience
Authors: Tran Pham Toan Khanh
Published: February 2025

Purpose

Based on the conservation of resources (COR) theory, this study explores the impact of tyrannical leadership on knowledge hiding through the mediating role of psychological distress. Furthermore, this study investigates the moderating role of psychological resilience in the tyrannical leadership, psychological distress and knowledge hiding relationships.

Design/methodology/approach

Quantitative data were collected from 364 employees working in the manufacturing and service sectors in Vietnam. Partial least squares structural equation modeling (PLS-SEM) was employed to test the proposed model.

Findings

The results show that tyrannical leadership and psychological distress enhance employees’ knowledge-hiding behaviors. Moreover, psychological distress mediates the nexus between tyrannical leadership and knowledge-hiding, while psychological resilience moderates these relationships.

Practical implications

The empirical findings of this investigation offer significant insights for managers to better undermine the negative effects of tyrannical leadership and enhance the psychological well-being of employees.

Originality/value

This study is probably the first attempt to explore how psychological distress mediates the impact of tyrannical leadership on knowledge hiding. This study also extends the current knowledge by considering the moderating role of psychological resilience in the relations between tyrannical leadership, psychological distress and knowledge hiding.
Sustainability consciousness, peer influence and sustainable consumption behaviour: the role of altruism among business students in Ghana
Authors: Sabah Welbeck Edem Emerald , Larbi Emmanuel Amemeotia
Published: February 2025

Purpose

This study aims to assess the impact of sustainability consciousness, altruism and peer influence on sustainable consumption behaviour of young adults.

Design/methodology/approach

Structured questionnaires were administered to 452 undergraduate students attending public universities in the southern part of Ghana. Partial least square structural equation modelling was used to test and analyse the hypothesized relationships.

Findings

Findings from this study indicate that sustainability consciousness and altruism significantly influence sustainable consumption. The respondents also suggest that their association with peers does not significantly affect sustainable consumption. Finally, the outcome of the analysis revealed that altruism partially mediates the nexus between sustainability consciousness and sustainable consumption.

Originality/value

The research directs attention to how the behaviour of undergraduate students who are sympathetic to the environment may influence their consumption behaviours. This study also demonstrates that sustainability awareness and knowledge by individuals play a vital role in shaping consumption behaviour, which may ultimately preserve resources for future generations.