bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Physical Activity from Wearable Devices and Chronic Disease Risk: Insights from the All of Us Research Program
Authors: Hou Yu , Cui Erjia , Ikramuddin Sayeed , Zhang Rui
Published: November 2024

Background

Physical activity is widely recognized as a key modifiable factor for reducing the risk of chronic diseases. Wearable devices such as Fitbit offer a unique opportunity to objectively measure physical activity metrics, providing insights into the association between different types of physical activity and chronic disease risk.

Objective

This study aims to examine the association between physical activity metrics derived from Fitbit devices and the incidence of various chronic diseases among participants from the All of Us Research Program.

Methods

Physical activity metrics included daily steps, elevation gain, and activity durations at different intensities (e.g., very active, lightly active, and sedentary). Cox proportional hazards models and multiple regression models were used to assess the relationship between these metrics and the incidence of chronic diseases represented by Phecodes. Age, sex, and body mass index (BMI) were included as covariates.

Results

A total of 15,538 participants provided Fitbit activity data, of which 9,320 also had electronic health records (EHR). Increased daily step count, elevation gain, and very active minutes were significantly associated with a reduced risk of several chronic conditions, including obesity, Type 2 diabetes, and major depressive disorder. Conversely, increased sedentary time was linked to higher risks for conditions such as obesity, Type 2 diabetes, and essential hypertension. Multiple regression analyses confirmed these associations.

Conclusion

Our findings highlight the beneficial effects of increased physical activity, particularly daily steps and elevation gain, on reducing the risk of chronic diseases. Conversely, sedentary behavior remains a significant risk factor for the development of several conditions. These insights may inform personalized activity recommendations aimed at reducing disease burden and improving population health outcomes.
Granger causality connectivity analysis of persistent atrial fibrillation dynamics reveals mechanistic insights into the posterior wall
Authors: Barker Joseph , Sau Arunashis , Bajaj Nikesh , Jenkins Alex , Sharp Alex , Shi Xili , Li Xinyang , Karim Nabeela , Handa Balvinder , Chambers Richard , Betts Timothy , Peters Nicholas S , Wong Tom , Ng Fu Siong
Published: November 2024

Background

Pulmonary vein isolation (PVI) is the mainstay of ablation for atrial fibrillation (AF). Adjunctive posterior wall isolation (PWI) has not demonstrated convincing additional benefit. To provide mechanistic underpinnings as to why empirical PWI does not improve outcomes, we undertook Granger Causality (GC) analysis of patient-specific AF dynamics before and after ablation.

Methods

A prospective cohort study was undertaken at Royal Brompton Hospital. Consecutive patients undergoing PVI with left atrial electro-anatomical noncontact mapping (AcQmap; Acutus Medical) were included. GC analysis was undertaken before and after PVI but before adjunctive ablation.

Results

In 21 consecutive patients, Causality Pairing Index, a Granger Causality-based measure of AF organisation, was unchanged post PVI; overall 0.087±0.012 vs. 0.086±0.015, p = 0.64, or by region (posterior wall; 0.084±0.020 vs 0.079±0.017, p = 0.20, rest of LA 0.087±0.013 vs 0.086±0.016, p = 0.80). Directional dispersion, quantifying conduction heterogeneity, was lower in the PW compared to the rest of the LA (0.093±0.036 vs 0.11±0.043, p = 0.017) and increased following PVI (0.093±0.036 vs 0.12±0.043, p = 0.045), while there was no change in the rest of the LA (0.11±0.034 vs 0.11±0.030, p =0.52). Net outflow for left atrial posterior wall decreased following PVI (pre −0.0086±0.047 vs −0.033±0.054, p=0.011), suggesting that in the majority of cases the posterior wall becomes a net sink after PVI

Conclusion

We describe the first application of GC to global, simultaneous AF mapping data. GC analysis suggests, on average, the posterior wall is a net sink following PVI, and therefore PWI will not be beneficial in the majority of patients, providing mechanistic insight into null randomised control trials for PWI. GC is positioned as a valuable clinical decision tool to select the minority of patients that may benefit from PWI to guide personalised PsAF ablation strategies.

Clinical Perspective

What is Known:

Pulmonary vein isolation (PVI) is a standard treatment for atrial fibrillation (AF) ablation, but adjunctive posterior wall isolation (PWI) has not demonstrated consistent additional clinical benefit.

What the Study Adds:

Granger Causality analysis of AF dynamics indicates that, following PVI, the left atrial posterior wall becomes a net sink in most cases.

This finding provides mechanistic insight into why PWI does not improve outcomes for most patients, explaining the null results in randomised trials.

The study supports using Granger Causality as a decision tool to personalise ablation strategies, identifying the minority of patients who may benefit from PWI.

Graphical Abstract
Sex-Related Differences in Endovascular Treatment Outcomes for Acute Large Infarcts: The ANGEL-ASPECT Subgroup Analysis
Authors: Sun Dapeng , Guo Xin , Jiao Liwen , Nguyen Thanh N , Abdalkader Mohamad , Pan Yuesong , Wang Mengxing , Luo Gang , Jia Baixue , Tong Xu , Ma Ning , Gao Feng , Mo Dapeng , Raynald  , Huo Xiaochuan , Miao Zhongrong ,   ANGEL-ASPECT study group
Published: November 2024

Background and Purpose

The outcomes of endovascular therapy (EVT) across sexes for large infarcts remains unclear. This study aimed to evaluate the impact of sex on the outcomes of EVT for patients with large infarct.

Methods

In this secondary analysis of the ANGEL-ASPECT trial, we compared baseline characteristics and clinical outcomes between men and women, and each cohort further divided into EVT and medical management (MM) groups. The primary outcome was the 90-day modified Rankin Scale (mRS) score distribution. Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 48 h and mortality within 90 days.

Results

There were 177 of 455 patients enrolled in the ANGEL-ASPECT trial who were women. 53.7% (95/177) of women and 48.6% (135/278) of men underwent EVT, respectively. The treatment effect of EVT didn’t vary in both sexes with large infarcts (all P >0.05 for interaction). Compared to MM, EVT improved 90-day functional outcomes for both men (3[2-5] vs. 4[3-5], common odds ratio [cOR]: 1.92, 95% CI: 1.26–2.95, P=0.003) and women (4[3-6] vs. 5[4-6], cOR: 2.50, 95% CI: 1.41–4.44, P=0.002). The sICH rate wasn’t different in both treatment groups across both sexes (Men: 5.2% vs. 2.8%, RR: 2.04, 95%CI: 0.56-7.47, P=0.28; Women:7.4% vs. 2.4%, RR:3.00, 95%CI:0.57-15.68, P=0.19).

Conclusion

In patients with large ischemic infarct, the treatment effect of EVT didn’t differ between women and men, with better outcomes with EVT versus MM, without an increased risk of sICH. These findings emphasize the need for equal attention and care for both sexes with large infarcts in clinical practice.
GHT-SELEX demonstrates unexpectedly high intrinsic sequence specificity and complex DNA binding of many human transcription factors
Authors: Jolma Arttu , Hernandez-Corchado Aldo , Yang Ally W.H. , Fathi Ali , Laverty Kaitlin U. , Brechalov Alexander , Razavi Rozita , Albu Mihai , Zheng Hong ,   The Codebook Consortium, Kulakovskiy Ivan V. , Najafabadi Hamed S. , Hughes Timothy R.
Published: November 2024

A long-standing challenge in human regulatory genomics is that transcription factor (TF) DNA-binding motifs are short and degenerate, while the genome is large. Motif scans therefore produce many false-positive binding site predictions. By surveying 179 TFs across 25 families using >1,500 cyclicin vitroselection experiments with fragmented, naked, and unmodified genomic DNA – a method we term GHT-SELEX (Genomic HT-SELEX) – we find that many human TFs possess much higher sequence specificity than anticipated. Moreover, genomic binding regions from GHT-SELEX are often surprisingly similar to those obtainedin vivo(i.e. ChIP-seq peaks). We find that comparable specificity can also be obtained from motif scans, but performance is highly dependent on derivation and use of the motifs, including accounting for multiple local matches in the scans. We also observe alternative engagement of multiple DNA-binding domains within the same protein: long C2H2 zinc finger proteins often utilize modular DNA recognition, engaging different subsets of their DNA binding domain (DBD) arrays to recognize multiple types of distinct target sites, frequently evolving via internal duplication and divergence of one or more DBDs. Thus, contrary to conventional wisdom, it is common for TFs to possess sufficient intrinsic specificity to independently delineate cellular targets.
Elovl1 inhibition reduced very long chain fatty acids in a mouse model of adrenoleukodystrophy
Authors: Huang Jeremy Y. , Freed Brian , Hanus Martin , Keefe Kelly , Chiang Ming Sum Ruby , Brezzani Alexander , Luo Yongyi , Li Yihang , Lam Becky , Holley Stephanie , Gans Joseph , Dostalova Zuzana , Tang Buyun , Phaneuf Clifford , Teeple Erin , Parisi Laura , Guo Lilu , Zhao Zhonglin , Kinton Sofia N. , Dwyer Jacquelyn , Teixeira Sandrine , Ma Hong , Asmussen Gary , McLaren Rajashree , Wang Donghui , Baker Ann , Siegel Craig S. , Fink David , Randall Kristen , Belenky Alexei , Venugopal Suchitra , Gaglia Giorgio , Johnson Jennifer , Bangari Dinesh S. , Sardi S. Pablo , Zhang Bailin , Michel Alexander , Proto Jonathan D. , Kloss Alla , Gladysheva Tatiana , Kayatekin Can
Published: November 2024

Adrenoleukodystrophy (ALD) is a rare neurometabolic disease caused by mutations in theABCD1gene, which encodes for the peroxisomal very long chain fatty acid (VLCFAs) transporter. It is a debilitating disorder, which has a spectrum of clinical presentations. The most severe form is a rapidly progressing demyelinating disease called cerebral ALD or CALD. Patients with cALD have a life expectancy of 2-4 years after onset and symptoms often manifest in childhood. The other forms are adrenomyeloneuropathy or AMN, which is a slower progressing degeneration of the spinal cord, and adrenal insufficiency (Addison disease). Since the accumulation of VLCFAs are a common factor in all ALD pathologies, we identified therapeutic approach that could correct this metabolic defect. We developed a substrate reduction therapy (SRT) for ALD in the form of an inhibitor of the lipid elongase principally responsible for the generation of VLCFAs, Elovl1. This small molecule was able to successfully reduce the accumulation of VLCFA in the brain and spinal cord ofABCD1−/ymice. We used single nuclei RNA seq to identify the pathways altered in theABCD1−/ymouse and corrected with Elovl1 inhibition. Though many lipid metabolism genes and pathways were indeed corrected, treatment with the Elovl1 inhibitor unexpectedly led to profound transcriptional changes beyond correction of pathways altered by loss ofABCD1. These data suggest that Elovl1 inhibition may have broader consequences inABCD1−/ymice than correction of lipid homeostasis.
An integrative approach to prioritize candidate causal genes for complex traits in cattle
Authors: Ghoreishifar Mohammad , Macleod Iona M. , Chamberlain Amanda J. , Liu Zhiqian , Lopdell Thomas J. , Littlejohn Mathew D. , Xiang Ruidong , Pryce Jennie E. , Goddard Michael E.
Published: November 2024

Genome-wide association studies (GWAS) have identified many quantitative trait loci (QTL) associated with complex traits, predominantly in non-coding regions, posing challenges in pinpointing the causal variants and their target genes. Three types of evidence can help identify the gene through which QTL act: (1) proximity to the most significant GWAS variant, (2) correlation of gene expression with the trait, and (3) the gene’s physiological role in the trait. However, there is still uncertainty in the success of these methods in identifying the correct genes. Here we test the ability of these methods in a comparatively simple series of traits associated with the concentration of polar lipids in milk.

We conducted single-trait GWAS for ∼14 million imputed variants and 56 individual milk polar lipid (PL) phenotypes in 336 cows. A meta-analysis of multi-trait GWAS identified 10,063 significant SNPs at FDR ≤ 10% (P≤ 7.15E-5). Transcriptome data from blood (∼12.5K genes, 143 cows) and mammary tissue (∼12.2K genes, 169 cows) were analysed using the genetic score omics regression (GSOR) method. This method links observed gene expression to genetically predicted phenotypes and was used to find associations between gene expression and 56 PL phenotypes. GSOR identified 2,186 genes in blood and 1,404 in mammary tissue associated with at least one PL phenotype (FDR ≤ 1%). We partitioned the genome into non-overlapping windows of 100 Kb to test for overlap between GSOR-identified genes and GWAS signals. We found a significant overlap between these two datasets, indicating GSOR significant genes were more likely to be located within 100 Kb windows that have GWAS signals compared to those without (P= 0.01; odds ratio = 1.47). These windows included 70 significant genes expressed in mammary tissue and 95 in blood. Compared to all expressed genes in each tissue, these genes were enriched for lipid metabolism gene ontology (GO). That is, 7 of the 70 significant mammary transcriptome genes (P< 0.01; odds ratio = 3.98) and 5 of the 95 significant blood genes (P< 0.10; odds ratio = 2.24) were involved in lipid metabolism GO. The candidate causal genes includeDGAT1,ACSM5,SERINC5,ABHD3,CYP2U1,PIGL,ARV1,SMPD5, andNPC2, with some overlap between the two tissues.

The overlap between GWAS, GSOR, and GO analyses suggests that together these methods can identify genes mediating QTL, though their power remains limited, as reflected by modest odds ratios. Larger sample sizes would enhance the power of these analyses, but issues like linkage disequilibrium would remain.
System-level characterization of engineered and evolved formatotrophicE. colistrains
Authors: Yilmaz Suzan , Kanis Boas , Hogers Rensco A. H. , Benito-Vaquerizo Sara , Kahnt Jörg , Glatter Timo , Dronsella Beau , Erb Tobias J. , Suarez-Diez Maria , Claassens Nico J.
Published: November 2024

One-carbon compounds, such as formate, are promising and sustainable feedstocks for microbial bioproduction of fuels and chemicals. Growth ofEscherichia colion formate was recently achieved by introducing the reductive glycine pathway (rGlyP) into its genome, which is theoretically the most energy-efficient aerobic formate assimilation pathway. While adaptive laboratory evolution was used to enhance the growth rate and biomass yield significantly, still the best performing formatotrophicE. colistrain did not approach the theoretical optimal biomass yield of the rGlyP. In this study, we investigated these previously engineered formatotrophicE. colistrains to find out why the biomass yield was sub-optimal and how it may be improved. Through a combination of metabolic modelling, genomic and proteomic analysis, we identified several potential metabolic bottlenecks and future targets for optimization. This study also reveals further insights in the evolutionary mutations and related changes in proteome allocation that supported the already substantially improved growth of formatotrophicE. colistrain. This systems-level analysis provides key insights to realize high-yield, fast growing formatotrophic strains for future bioproduction.
A systematic and meta-analytic review of non-verbal auditory memory in the brain
Authors: Campo Fulvia Francesca , Carlomagno Francesco , Yılmaz Betül , Quaranta Luis , Carraturo Giulio , Rivolta Davide , Brattico Elvira
Published: November 2024

While sounds are essential for human development, existing research primarily emphasizes visual and spatial memory and speech in relation to auditory processes, with a lack of a cohesive understanding of memory mechanisms for non-verbal sounds. This systematic review and coordinate-based meta-analysis of neuroimaging findings aims to comprehensively organize the literature for identifying the key brain mechanisms involved in short-term memory, working memory, and long-term memory for non-verbal auditory information. Additionally, we aimed to identify whether and how individual differences in neural memory processes related to auditory expertise (musicianship), aging or auditory impairments such as amusia are explored in the literature. Our review included ninety studies meeting the selection criteria, with only thirteen studies containing brain coordinates could be included in the meta-analysis. The coordinate-based meta-analysis identified a frontal hub for non-verbal auditory memory encompassing the medial frontal gyrus, cingulate gyrus and superior frontal gyrus.
UniOP: a universal operon prediction for high-throughput prokaryotic (meta-)genomic data using intergenic distance
Authors: Su Hong , Zhang Ruoshi , Söding Johannes
Published: November 2024

The study of the deluge of metagenomic and genomic sequences is challenging due to the severe lack of function information. Predicting operons, groups of functionally related genes in prokaryotic genomes, is critical for bridging this gap. However, existing methods for operon prediction heavily rely on experimental data, functional annotations, or extensive characterization of homologous genes, making it difficult to accurately predict operons in newly sequenced or poorly characterized genomes. Here, we introduce UniOP, an unsupervised approach that uses a statistical model to predict operons from intergenic distances directly derived from the target genomic sequence. UniOP not only outperforms alternative approaches on ten complete genomes but also shows superior results on 3269 metagenome-assembled genomes across 13 bacterial and 2 archaeal phyla. Furthermore, we explored enhancing UniOP by incorporating the conservation of gene neighborhood and strandedness in respective genomes and examined the influence of Pfam annotations and motif searching on its performance.
Single-cell spatial transcriptomics of fixed, paraffin-embedded biopsies reveals colitis-associated cell networks
Authors: Mennillo Elvira , Lotstein Madison L. , Lee Gyehyun , Johri Vrinda , Ekstrand Christina , Tsui Jessica , Hou Julian , Leet Donna E. , He Jun Yan , Mahadevan Uma , Eckalbar Walter , Oh David Y. , Fragiadakis Gabriela K. , Kattah Michael G. , Combes Alexis J.
Published: November 2024

Background & Aims

Imaging-based, single-cell spatial transcriptomics (iSCST) using formalin-fixed, paraffin-embedded (FFPE) tissue could transform translational research by retaining all tissue cell subsets and spatial locations while enabling the analysis of archived specimens. We aimed to develop a robust framework for applying iSCST to archived clinical FFPE mucosal biopsies from patients with inflammatory bowel disease (IBD).

Methods

We performed a comprehensive benchmarking comparison of three iSCST platforms capable of analyzing FFPE specimens. We analyzed FFPE mucosal biopsies (n=57) up to 5 years old from non-IBD controls (HC; n=9) and patients with ulcerative colitis (UC;n=11). After platform-specific cell segmentation, we applied a uniform data processing pipeline to all datasets, including transcript detection, cell annotation, differential gene expression, and neighborhood enrichment. Transcriptomic signatures identified with iSCST were validated using external, publicly available bulk transcriptomic datasets.

Results

A custom 290-plex Xenium gene panel exhibited the highest sensitivity and specificity for transcript detection, enabling precise identification and quantification of diverse cell subsets and differentially expressed genes across cell types and disease states. We mapped transcriptionally distinct fibroblast subsets to discrete spatial locations and identified inflammation-associated fibroblasts (IAFs) and monocytes as a colitis-associated cellular neighborhood. We also identified signatures associated with Vedolizumab (VDZ) responsiveness. VDZ non-responders were characterized by an IAF-monocyte transcriptional signature, while responders exhibited enrichment of epithelial gene sets.

Conclusions

Our optimized iSCST framework for archived FFPE biopsies provides unique advantages for assessing the role of colitis-associated cellular networks in routinely collected clinical samples. FFPE-based biomarkers could integrate with existing clinical workflows and potentially aid in risk-stratifying patients.
SIMPL: Scalable and hassle-free optimization of neural representations from behaviour
Authors: George Tom M , Glaser Pierre , Stachenfeld Kimberly , Barry Caswell , Clopath Claudia
Published: November 2024

Abstract

High-dimensional neural activity in the brain is known to encode low-dimensional, time-evolving, behaviour-related variables. A fundamental goal of neural data analysis consists of identifying such variables and their mapping to neural activity. The canonical approach is to assume the latent variablesarebehaviour and visualize the subsequent tuning curves. However, significant mismatches between behaviour and the encoded variables may still exist — the agent may be thinking of another location, or be uncertain of its own — distorting the tuning curves and decreasing their interpretability. To address this issue a variety of methods have been proposed to learn this latent variable in an unsupervised manner; these techniques are typically expensive to train, come with many hyperparameters or scale poorly to large datasets complicating their adoption in practice. To solve these issues we propose SIMPL (Scalable Iterative Maximization of Population-coded Latents), an EM-style algorithm which iteratively optimizes latent variables and tuning curves. SIMPL is fast, scalable and exploits behaviour as an initial condition to further improve convergence and identifiability. We show SIMPL accurately recovers latent variables in biologically-inspired spatial and non-spatial tasks. When applied to a large rodent hippocampal dataset SIMPL efficiently finds a modified latent space with smaller, more numerous, and more uniformly-sized place fields than those based on behaviour, suggesting the brain may encode space with greater resolution than previously thought.
Nimodipine reduces microglial activationin vitroas evidenced by morphological phenotype, phagocytic activity and next generation RNA sequencing
Authors: Pesti István , Varga Valentin , Qorri Erda , Frank Rita , Kata Diana , Vinga Krisztián , Szarvas Péter Archibald , Menyhárt Ákos , Gulya Károly , Bari Ferenc , Farkas Eszter
Published: November 2024

Background

Nimodipine, an L-type voltage-gated calcium channel blocker, achieves vasorelaxation by suppressing Ca2+-dependent activation of cerebrovascular smooth muscle cells and is used to prevent delayed ischemic deficit following subarachnoid hemorrhage. Our preclinical drug repurposing studies raised the possibility that nimodipine may attenuate the pro-inflammatory shift in microglial function in response to brain injury. We analyzed the effects of nimodipine on activated microglia at the level of morphological and functional phenotypes, as well as their transcriptomic profile.

Methods

Live brain slice preparations from C57BL/6 mice and primary microglia cultures from the cortex of neonatal Sprague Dawley rats were used. Brain slices were subjected to ischemia, and microglial cultures were activated with lipopolysaccharide (LPS; 20 ng/ml). Both preparations were treated with nimodipine (5-10-20 μM). The degree of arborization was evaluated in Iba1-stained microglia and expressed as a transformation index (TI). Phagocytic activity of cultured microglia was visualized using fluorescent microbeads. TNFα levels in the cultures were measured with ELISA. Total RNA was isolated from microglia and processed for next generation RNA sequencing to determine differentially expressed genes.

Results

Nimodipine suppressed the ameboid morphological transformation and increased phagocytosis triggered by ischemia in brain slices and LPS in microglia cultures. At the transcriptional level, LPS resulted in a pro-inflammatory microglial phenotype, affecting the expression of cytokines, the complement system and phagocytosis-related genes. Focusing on the role of calcium in microglial activation, LPS increased RNA transcription of ionotropic purinergic and some TRP channels but decreased the expression of voltage- and ligand-gated calcium channels. In the endoplasmic reticulum, LPS downregulated gene expression of Ryr and IP3 receptors and increased transcription of the SERCA calcium pump gene. Nimodipine co-administered with LPS altered the expression of 110 genes in the opposite direction to LPS activation, of which at least 20 were associated with microglial immune response, 7 with cell adhesion and 2 with autophagy regulation.

Conclusion

The effect of nimodipine goes beyond cerebral vasorelaxation. Nimodipine attenuates microglial activation by modulating Ca2+-dependent gene expression involved in intracellular signaling cascades to drive microglial immune responses. Consideration should be given to expanding the medical field of indication of nimodipine.
A translocation-competent pore is required forShigella flexnerito escape from the double membrane vacuole during intercellular spread
Authors: Raab Julie E. , Harju Tucker B. , Toperzer Jody D. , Duncan-Lowey Jeffrey K. , Goldberg Marcia B. , Russo Brian C.
Published: November 2024

Type 3 secretion systems (T3SSs) enable bacterial virulence by translocating virulence proteins (effectors) into host cells.Shigella flexnerirequire T3SS to invade and to spread between cells in the colon. In order to spread,S. flexneriforms membrane protrusions that push into the adjacent host cell. These protrusions are resolved into double membrane vacuoles (DMVs) that the bacteria quickly escape. The mechanisms required for escape from the DMV are poorly understood, but the T3SS translocon pore protein IpaC is essential. Here, we show IpaC forms a pore that is competent for translocation of T3SS effectors as bacteria spread between cells. To do so, we used a genetic approach to test mutations of IpaC that disrupt its ability to translocate and to form pores. We show that during spread, IpaC is efficiently inserted into the plasma membrane, the membrane-embedded IpaC forms pore complexes, and the IpaC-dependent pores translocate effectors that are necessary forS. flexnerito escape the DMV. We further show that T3SS activation is regulated through a distinct mechanism at spread compared to at invasion; activation of T3SS secretion does not require pore formation during spread. Thus, we show that a distinct regulation of the T3SS duringS. flexneriintercellular spread enables the placement of effectors both aroundS. flexneriand across membranes of the DMV. Altogether, this study provides new insights into howS. flexneriescapes the DMV.

IMPORTANCE

The type 3 secretion system (T3SS) is required for virulence in many bacterial pathogens that infect humans. The T3SS forms a pore through which virulence proteins are delivered into host cells to enable bacterial infection. Our work investigates theShigellatranslocon pore protein IpaC, which is essential not only for bacteria to invade cells, but also for bacteria to spread between cells. An ability to spread between cells is essential for pathogenesis, thus understanding the mechanisms that enable spread is important for understanding howS. flexneriinfection causes illness. We show that IpaC delivers virulence factors across the host membrane forS. flexnerito efficiently spread. This study furthers our understanding of the mechanisms involved in T3SS secretion and of translocon pore function duringS. flexneriintercellular spread.
A toolkit for testing membrane localisation tags across species
Authors: Karapidaki Irene , Momose Tsuyoshi , Zilliox Marie , Averof Michalis
Published: November 2024

Transgenic markers and tools have revolutionised how we study cells and developing organisms. Some of the elements needed to construct those tools are universally applicable (e.g. fluorescent proteins), while others are species-specific (e.g.cis-regulatory elements driving transcription). Membrane localisation signals targeting proteins to the plasma membrane have been identified in several model organisms. Unfortunately, these do not work equally well in different species, developmental stages and cell types. To generate a toolkit of membrane localisation tags that can be screened rapidly in diverse species, we collected 11 membrane localisation tags –known to localise proteins to the plasma membrane through different mechanisms– and fused them to the red fluorescent protein mScarlet3. Each tagged construct was placed downstream of a T7 promoter, allowing thein vitroproduction of tagged reporter mRNAs, which can be readily delivered to embryos or cell types of interest. The tags in this kit include signals for trafficking to the plasma membrane through the exocytic pathway with a transmembrane domain (SP-CD8tm) or a GPI anchor (SP-GPI), lipid-binding domains (PH, LactC2), signals for prenylation, palmitoylation and myristoylation (H-Ras, K-Ras, K-Ras-6R, GAP43, Lyn, Src64B), and a domain that targets proteins to the plasma membrane independently of exocytosis or lipid modification (RitC). We demonstrate the use of this toolkit in early embryos of the crustaceanParhyale hawaiensisand primary polyps of the hydrozoanClytia hemisphaerica.
Bonding states underpinning structural transitions in
IrTe2
observed with micro-ARPES
Authors: Nicholson C. W. , Watson M. D. , Pulkkinen A. , Rumo M. , Kremer G. , Ma K. Y. , von Rohr F. O. , Cacho C. , Monney C.
Published: November 2024

Competing interactions in low-dimensional materials can produce nearly degenerate electronic and structural phases. We investigate structural phase transitions in layered IrTe2 for which a number of potential transition mechanisms have been postulated. The spatial coexistence of multiple phases on the micron scale has prevented a detailed analysis of the electronic structure. By exploiting micro-angle-resolved photoemission spectroscopy obtained with synchrotron radiation we extract the electronic structure of the multiple structural phases in IrTe2 in order to address the mechanism underlying the phase transitions. We find direct evidence of lowered energy states that appear in the low-temperature phases, states previously predicted by calculations and extended here. Our results validate a proposed scenario of bonding and antibonding states as the driver of the phase transitions.

Published by the American Physical Society
2024
resbos2 and the CDF
W
mass measurement
Authors: Isaacson Joshua , Fu Yao , Yuan C.-P.
Published: November 2024

The recent collider detector at fermilab (CDF) W mass measurement of 80,433±9  MeV is the most precise direct measurement. However, this result deviates from the Standard Model predicted mass of 80,359.1±5.2  MeV by 7σ. The CDF experiment used an older version of the esos code that was only accurate at NNLL+NLO, while the esos2 code is able to make predictions at N3LL+NNLO accuracy. We determine that the data-driven techniques used by CDF capture most of the higher order corrections, and using higher order corrections would have an impact on the CDF result in total at the 10 MeV level. Additionally, we investigate the effects from handling the width of the W boson on the mass, PDF correlations, and scale uncertainties. We find that these contributions are consistent with those obtained by CDF.

Published by the American Physical Society
2024
Dark matter as the trigger of flavor changing neutral current decays of the top quark
Authors: Jueid Adil , Kanemura Shinya
Published: November 2024

We suggest a simplified model that simultaneously addresses the dark matter problem and gives rise to top-quark flavor changing neutral current (FCNC) interactions at the one-loop order. The model consists of two extra SU(2)L gauge singlets: a colored mediator of spin zero (S) and a right-handed fermion (χ); both are odd under an Z2 symmetry. The right-handed fermion plays the role of the dark matter candidate. In this model, the presence of the two dark sector particles generates one-loop induced FCNC decays of the top quark into light quarks and bosons such as the gluon, the photon, the Z boson, or the Higgs boson. As a case study, we analyze the top-quark FCNC decays into light quarks (u or c) and Z or Higgs bosons. We then study the reliable solutions to the dark matter problem by estimating the regions in the parameter space that are consistent with the measurement of the dark matter relic density. We also revisit the bounds from the searches of dark matter in events with at least one high-pT jet and large missing transverse energy at the Large Hadron Collider (LHC). We then define four benchmark points that are consistent with the existing constraints from collider experiments and cosmology. We finally estimate, for these benchmark scenarios, the rates of a broad range of channels that can be used to probe the connection between the top FCNC transitions and dark matter, both at the HL-LHC and at a future 100 TeV collider.

Published by the American Physical Society
2024
Muonic force and nonstandard neutrino interactions at muon colliders
Authors: Jana Sudip , Klett Sophie
Published: November 2024

The discovery of neutrino oscillations implies that neutrinos are massive and mixed, necessitating an extension of the Standard Model, which may require the introduction of nonstandard neutrino interactions (NSIs). We investigate the potential of a high-energy muon collider to probe such NSIs with muons, specifically focusing on muonic forces. By analyzing the monophoton signal from the process μ+μ−→νν¯γ, we explore four-fermion contact interactions involving two muons and two neutrinos. Moreover, we examine minimal models that generate scalar and vector-mediated NSIs and study their phenomenology. Projected sensitivities for the strength of NSIs, εαβμμ, are presented at a 95% confidence level for a center-of-mass energy of 3 TeV and integrated luminosities of L=1 and 10  ab−1, showcasing the complementarity between a muon collider and other experimental probes.

Published by the American Physical Society
2024
Double and triple Higgs boson production to probe the electroweak phase transition
Authors: Biermann Lisa , Borschensky Christoph , Englert Christoph , Mühlleitner Margarete , Naskar Wrishik
Published: November 2024

The production of three Higgs bosons could be a stretch goal for the LHC and a strategic case for future colliders. In this work, we analyse the phenomenological prospects of (neutral) triple Higgs compared to di-Higgs boson production, for a range of Higgs-sector extensions from a strong first-order electroweak phase transition perspective. In parallel, we include constraints from existing exotics and Higgs boson measurements that further limit the parameter space of such models. Resonance contributions offer large modifications in particular for triple Higgs production, albeit starting from a small SM expectation. With enhancements of order 40 over the SM, however, experimental efforts to obtain limits at the HL-LHC are well motivated and well placed. This is further highlighted by the potential of these processes to inform the investigation of the thermal history of our Universe.

Published by the American Physical Society
2024
Dark matter limits from the tip of the red giant branch of globular clusters
Authors: Hong Haozhi , Vincent Aaron C.
Published: November 2024

Capture and annihilation of weakly interacting massive particle (WIMP)-like dark matter in red giant stars can lead to faster-than-expected ignition of the helium core, and thus a lower tip of the red giant branch (TRGB) luminosity. We use data to place constraints on the dark matter-nucleon cross section using 22 globular clusters with measured TRGB luminosities, and place projections on the sensitivity resulting from 161 clusters with full phase space distributions observed by . Although limits remain weaker than those from Earth-based direct detection experiments, they represent a constraint that is fully independent of dark matter properties in the solar neighborhood, probing its properties across the entire Milky Way galaxy. Based on our findings, it is likely that the use of the TRGB as a standard candle in H0 measurements is very robust against the effects of dark matter.

Published by the American Physical Society
2024
Can one hear the shape of a crystal?
Authors: Wang Haina , Torquato Salvatore
Published: November 2024

Isospectrality is a general fundamental concept often involving whether various operators can have identical spectra, i.e., the same set of eigenvalues. In the context of the Laplacian operator, the famous question “Can one hear the shape of a drum?” concerns whether different shaped drums can have the same vibrational modes. The isospectrality of a lattice in d-dimensional Euclidean space Rd is a tantamount to whether it is uniquely determined by its theta series, i.e., the radial distribution function g2(r). While much is known about the isospectrality of Bravais lattices across dimensions, little is known about this question of more general crystal (periodic) structures with an n-particle basis (n≥2). Here, we ask what is nmin(d), the minimum value of n for inequivalent (i.e., unrelated by isometric symmetries) crystals with the same theta function in space dimension d? To answer these questions, we use rigorous methods as well as a precise numerical algorithm that enables us to determine the minimum multiparticle basis of inequivalent isospectral crystals. Our algorithm identifies isospectral four-, three- and two-particle bases in one, two, and three spatial dimensions, respectively. For many of these isospectral crystals, we rigorously show that they indeed possess identically the same g2(r)'s for all values of r. Based on our analyses, we conjecture that nmin(d)=4, 3, 2 for d=1, 2, 3, respectively. The identification of isospectral crystals enables one to study the degeneracy of the ground-state under the action of isotropic pair potentials. Indeed, using inverse statistical-mechanical techniques, we find an isotropic pair potential whose low-temperature configurations in two dimensions obtained via simulated annealing can lead to both of two isospectral crystal structures with n=3, the proportion of which can be controlled by the cooling rate. Our findings provide general insights into the structural and ground-state degeneracies of crystal structures as determined by radial pair information.

Published by the American Physical Society
2024
Parent Berry Curvature and the Ideal Anomalous Hall Crystal
Authors: Tan Tixuan , Devakul Trithep
Published: November 2024

We study a model of electrons moving in a parent band of uniform Berry curvature. At sufficiently high parent Berry curvature, we show that strong repulsive interactions generically lead to the formation of an anomalous Hall crystal: a topological state with spontaneously broken continuous translation symmetry. Our results are established via a mapping to a problem of Wigner crystallization in a regular 2D electron gas. Interestingly, we find that a periodic electrostatic potential induces a competing state with opposite Chern number. Our theory offers a unified perspective for understanding several aspects of the recently observed integer and fractional quantum anomalous Hall effects in rhombohedral multilayer graphene and provides a recipe for engineering new topological states.

Published by the American Physical Society
2024
Bifurcation Enhances Temporal Information Encoding in the Olfactory Periphery
Authors: Choi Kiri , Rosenbluth Will , Graf Isabella R. , Kadakia Nirag , Emonet Thierry
Published: November 2024

Living systems continually respond to signals from the surrounding environment. Survival requires that their responses adapt quickly and robustly to the changes in the environment. One particularly challenging example is olfactory navigation in turbulent plumes, where animals experience highly intermittent odor signals while odor concentration varies over many length- and timescales. Here, we show theoretically that olfactory receptor neurons (ORNs) can exploit proximity to a bifurcation point of their firing dynamics to reliably extract information about the timing and intensity of fluctuations in the odor signal, which have been shown to be critical for odor-guided navigation. Close to the bifurcation, the system is intrinsically invariant to signal variance, and information about the timing, duration, and intensity of odor fluctuations is transferred efficiently. Importantly, we find that proximity to the bifurcation is maintained by mean adaptation alone and therefore does not require any additional feedback mechanism or fine-tuning. Using a biophysical model with calcium-based feedback, we demonstrate that this mechanism can explain the measured adaptation characteristics of ORNs.

Published by the American Physical Society
2024
Who cares about environmental, social and governance performance? Family versus non-family firms
Authors: Zhao Jiyang , Wang Xiaohong
Published: November 2024

Purpose

This paper aims to explore the nexus between family involvement and environmental, social and governance (ESG) performance based on socioemotional wealth theory, and it also analyzes the potential influence mechanism.

Design/methodology/approach

Based on the categorization of China Stock Market & Accounting Research database, this study divides the Chinese listed firms into family and nonfamily firms and applies multiple regression methods to test the theoretical hypotheses.

Findings

Family involvement can incentivize corporations to enhance corporate transparency, which can in turn enhance their ESG performance. The role of family involvement in bolstering corporate ESG performance is negatively contingent on external financing constraints.

Originality/value

There are insufficient studies on the nexus between family ownership and ESG performance. The findings provide insights into helping policymakers formulate targeted measures to encourage corporations to be more active in promoting ESG initiatives.
Does language concreteness influence consumers’ perceived deception in online reviews?
Authors: Shi Xiaoxiao , Shan Wei , Du Zhaohua , Evans Richard David , Zhang Qingpu
Published: November 2024

Purpose

Although online reviews have become a key source of information for consumer purchasing decisions, little is known about how the concreteness of language used in these reviews influences perceptions of deception. This study aims to address this important gap by drawing on psycholinguistic research and Language Expectancy Theory to examine how and when the concreteness of online reviews (abstract vs concrete) impacts consumers’ perceived deception.

Design/methodology/approach

Two scenario-based experiments were conducted to examine how the concreteness of online reviews (abstract vs concrete) influences consumers’ perceptions of deception, considering the mediating role of psychological distance to online reviews and the moderating effects of Machiavellianism (Mach) and reviewer identity disclosure.

Findings

Online reviews that include concrete language lead to lower perceived deception by reducing consumers’ psychological distance from the review. For consumers with higher levels of Mach, online reviews written in abstract (vs concrete) language result in higher perceived deception via psychological distance, while for consumers with lower Mach, online reviews written in concrete (vs abstract) language result in higher perceived deception via psychological distance.

Research limitations/implications

To the best of the authors’ knowledge, this study is one of the first to highlight the relevance of linguistic style (i.e. concrete review vs abstract review) on consumers’ perceived deception toward online reviews in the context of e-commerce.

Practical implications

The framework enables managers of online retailing platforms to identify the most effective strategies to decrease consumers’ perceived deception via the appropriate utilize of linguistic styles of online reviews.

Originality/value

This study contributes to both theory and practice by deepening knowledge of how and when the concreteness of online reviews (abstract vs concrete) affects consumers’ perceived deception and by helping managers of online retailing platforms make the most effective\ strategies for reducing consumers’ perceived deception toward online reviews during online shopping.
During and after COVID-19: understanding entertainment consumption shifts through habit and customer value perspectives
Authors: Soren Anup Anurag
Published: November 2024

Purpose

As situational changes result in changing consumption patterns, this study aims to understand the entertainment consumption shifts during and after the COVID-19 pandemic lockdown. Particularly, how users’ habits and use behavior have changed and how these constructs subsequently impact their continuance intention has been investigated. The study proposes a research model based on customer value and habit theory.

Design/methodology/approach

The study proposes a research model based on customer value and habit theory. The data collected during (n = 192) and after (n = 138) COVID-19 situation in the over-the-top (OTT) platforms setting through purposive sampling was analyzed using partial least square structural equation modeling (PLS-SEM).

Findings

The study elucidates that customer perceived value (utilitarian and hedonic values) impacts habit and continuance intention in different situations: during and after COVID-19. It was also shown that habit partially mediates the influence of utilitarian and hedonic values on continuance intention. Further, the extent of use had a negative moderation effect on the habit-continuance intention relationship during COVID-19 but did not moderate the relationship in the post-COVID-19 situation. Finally, it was demonstrated that the effect of utilitarian value increased, whereas that of hedonic value decreased on the continuance intention of OTT platforms in the after-COVID-19 situation compared to during COVID-19.

Practical implications

Although set up in the OTT context, the practitioners from other online entertainment services, and any online service in general, may utilize the study findings to reinforce habit and continuance intentions to address unwanted consequences due to situational changes. The study suggests to the OTT service providers ways to facilitate the habit formation of OTT users. The study recommends constant monitoring of the extent of the use of OTT consumers and user engagement tactics for nurturing the OTT consumption habits of heavy users. The recommendations for maintaining and strengthening the perceived value-continuance intention relationship were also made, which would help the OTT service providers immensely.

Originality/value

The study establishes the mediation effect of habit and the robustness of perceived value in determining continuance intention in varying situations. The results also highlighted the changes in the impact of perceived value and habit on the continuance intention of OTT platforms. The study also advances the literature by demonstrating the differential influence of the extent of use on the habit-continuance intention relationship during and after COVID-19.