bluuebunny/crossref_metadata_2025 huggingface dataset:
The discovery of antimicrobial peptides from the gut microbiome of cockroachBlattella germanicausing deep learning pipeline
Authors: Chen Sizhe , Qi Huitang , Zhu Xingzhuo , Liu Tianxiang , Teng Yingda , Gong Qiuyu , Jia Cangzhi , Liu Tian , Chen S , Qi H , Zhu X , Liu T , Teng Y , Gong Q , Jia C , Liu T
Published: February 2024

Antimicrobial peptides (AMPs) are candidates for use against antibiotic-resistant microorganisms. However, due to high cytotoxicity and poor performance in biological contexts, most AMPs are unable to satisfy the requirements. The gut microbiomes of pathogenic species likeBlattella germanicarepresent unexploited reservoirs of naturally evolved biocompatible AMPs. Here we developed a lightweight AI pipeline called AMPidentifer with two nine-layers Dense-Net blocks and one embedded new self-attention module to enable the discovery of biocompatible AMPs from microbiome. The core structure of AMPidentifer is simple, not requiring complexing code basis. On the independent test dataset, it showed robust performance and avoided high false-positive results. From the gut microbiome ofB. germanica, new AMP candidates with potential low toxicities and antimicrobial activities were identified by AMPidentifer. The selected two AMPs demonstrated good antimicrobial effectsin vitroandin vivo. The Cys residue was demonstrated to perform different action mechanisms in the antimicrobial activity of two AMPs, providing insights for future rational design. New efficient AMPs with low cytotoxicity identified by the new high-throughput AI pipeline from the gut microbiome ofB. germanicasuccessfully showed an important interdisciplinary strategy for discovering bio-safe AMPs from nature.

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The Graphic Abstract
Contributions of short and long-range white matter tracts in dynamic compensation with aging
Authors: Chakraborty Priyanka , Saha Suman , Deco Gustavo , Banerjee Arpan , Roy Dipanjan
Published: February 2024

Brain function is shaped by the local and global connections between its dynamical units and biological parameters. With aging, the anatomical connectivity undergoes significant deterioration (e.g., long-range white matter fiber loss), which affects the brain’s overall function. Despite the structural loss, previous research has shown that normative patterns of functions remain intact across the lifespan, defined as the compensatory mechanism of the aging brain. However, the crucial components in guiding the compensatory preservation of the dynamical complexity and the underlying mechanisms remain uncovered. Moreover, it remains largely unknown how the brain readjusts its biological parameters to maintain optimal brain dynamics with age; in this work, we provide a parsimonious mechanism using a whole-brain generative model to uncover the role of sub-communities comprised of short-range and long-range connectivity in driving the dynamic compensation process in the aging brain. We utilize two neuroimaging datasets to demonstrate how short—and long-range white matter tracts affect compensatory mechanisms. We unveil their modulation of intrinsic global scaling parameters, such as global coupling strength and conduction delay, via a personalized large-scale brain model. Our two key findings suggest that (1) the optimal coupling strength and delay play complementary roles in preserving the brain’s optimal working state. (2) Short-range tracts predominantly amplify global coupling strength with age, potentially representing an epiphenomenon of the compensatory mechanism. This mechanistically explains the significance of short-range connections in compensating for the major loss of long-range connections during aging. This insight could help identify alternative avenues to address aging-related diseases where long-range connections are significantly deteriorated.
The unified proposal for classification of human respiratory syncytial virus below the subgroup level
Authors: Goya Stephanie , Ruis Christopher , Neher Richard A. , Meijer Adam , Aziz Ammar , Hinrichs Angie S. , von Gottberg Anne , Roemer Cornelius , Amoako Daniel G. , Acuña Dolores , McBroome Jakob , Otieno James R. , Bhiman Jinal N. , Everatt Josie , Muñoz-Escalante Juan C. , Ramaekers Kaat , Duggan Kate , Presser Lance D. , Urbanska Laura , Venter Marietjie , Wolter Nicole , Peret Teresa C. T. , Salimi Vahid , Potdar Varsha , Borges Vítor , Viegas Mariana
Published: February 2024

A globally implemented unified classification for human respiratory syncytial virus (HRSV) below the subgroup level remains elusive. Here, we formulate the global consensus of HRSV classification based on the challenges and limitations of our previous proposals and the future of genomic surveillance. From a high-quality dataset of 1,480 HRSV-A and 1,385 HRSV-B genomes submitted to NCBI and GISAID up to March 2023, we categorized HRSV-A/B sequences into lineages based on phylogenetic clades and amino acid markers. We defined 24 lineages within HRSV-A and 16 within HRSV-B, providing guidelines for prospective lineages definition. Our classification demonstrated robustness in its applicability to both complete and partial genomes. In addition, it allowed the observation of notable lineage replacements and the identification of lineages exclusively detected since the COVID-19 pandemic. We envision that this unified HRSV classification proposal will strengthen and facilitate HRSV molecular epidemiology on a global scale.
Enabling Advanced Multi-Modal Neuroimaging Analysis within a Trusted Research Environment
Authors: Hotchkiss L , Squires E , Gallacher J E , Newbury M , Morris C , Lyons RA , Thompson S
Published: February 2024

Introduction

Globally, 55 million individuals have dementia, with an increasing annual incident of 10 million. Enabling development of new multi-modal models can improve the current diagnostic pathways and potentially contribute to early diagnosis and treatment of dementia. Here, we report how multi-modal resources is achieved within the successful Trusted Research Environment (TRE) providing access to 60+ cohort datasets for dementia research, the Dementias Platform UK (DPUK).

Objectives

We aimed to identify the challenges of the storage, distribution and analysis of neuroimaging data and how we could implement a comprehensive infrastructure to deal with these. The problems we specifically aimed to address were how to: anonymise scans, store large amounts of data, standardise datasets to a common format, extract metadata, provision the data, and allow for analysis.

Methods

While, data within majority of existing research platforms are focused on a single aspect, DPUK data provides an enriched view of disease dynamic for dementia cohorts by providing access to linkable brain imaging and genomic data at the individual-level. We document various stages and capacities required for multi-modal neuroimaging analysis for dementia and conclude that achieving research ready assets to enable neuroimaging analysis for dementia from existing resources requires an engineered process to facilitate multiple aspects of curation, provisioning and large scale analysis.

Results

We developed an ingest pipeline for neuroimaging data to meet the requirements set out in the objectives. This involved standardising all datasets to the Brain Imaging Data Structure, defacing scans and anonymising data, using MinIO for data storage and extracting metadata from header information for data discovery and provisioning.

Conclusion

The neuroimaging ingest pipeline developed has allowed for the distribution of imaging datasets within DPUK which has facilitated multi-modal research on anonymised and standardised data. Our pipelines create research-ready datasets in a simplified way, reducing the time and effort of getting these datasets ready for data sharing and making the process easier for the data owners.
Difference in TMPRSS2 usage by Delta and Omicron variants of SARS-CoV-2: Implication for a sudden increase among children
Authors: Kakee Sosuke , Kanai Kyosuke , Tsuneki-Tokunaga Akeno , Okuno Keisuke , Namba Noriyuki , Tomita Katsuyuki , Chikumi Hiroki , Kageyama Seiji
Published: February 2024

It has been postulated from a combination of evidence that a sudden increase in COVID-19 cases among pediatric patients after onset of the Omicron wave was attributed to a reduced requirement for TMPRSS2-mediated entry in pediatric airways with lower expression levels of TMPRSS2. Epidemic strains were isolated from the indigenous population in an area, and the levels of TMPRSS2 required for Delta and Omicron variants were assessed. As a result, Delta variants proliferated fully in cultures of TMPRSS2-positive Vero cells but not in TMPRSS2-negative Vero cell culture (350-fold, Delta vs 9.6-fold, Omicron). There was no obvious age-dependent selection of Omicron strains affected by the TMPRSS2 (9.6-fold, Adults vs. 12-fold, Children). A phylogenetic tree was generated and Blast searches (up to 100 references) for the spread of strains in the study area showed that each strain had almost identical homology (>99.5%) with foreign isolates, although indigenous strains had obvious differences from each other. This suggested that the differences had been present abroad for a long period. Therefore, the lower requirement for TMPRSS2 by Omicron strains might be applicable to epidemic strains globally. In conclusion, the property of TMPRSS2-independent cleavage makes Omicron proliferate with ease and allows epidemics among children with fewer TMPRSS2 on epithelial surfaces of the respiratory organs.
Primary causes and direct medical cost of heart failure among adults admitted with acute decompensated heart failure in a public tertiary hospital, Kenya
Authors: Wauye Victor M. , Oduor Chrispine O. , Barasa Felix A. , Ngeno G. Titus
Published: February 2024

Heart failure (HF) is a major contributor of cardiovascular morbidity and mortality globally. Despite its adverse impact on health outcomes in low- and middle-income countries such as Kenya, data on the direct medical cost of HF hospitalization is limited.

This was a prospective study conducted at Moi Teaching and Referral Hospital. Patients with HF were identified by sequential medical chart abstraction. Primary causes were extracted from echocardiogram reports and adjudicated by a cardiologist. Direct medical cost of hospitalization was derived using activity-based costing, micro-costing method, and payers’ system perspective. Drivers of overall cost were explored using linear regression models.

142 participants were consecutively recruited from September to November 2022. 51.4% were females, and the overall mean age was 54 (SD 20). The leading primary cause was cor pulmonale (CP), 28.9%; then dilated cardiomyopathy (DCM), 26.1%; rheumatic heart disease (RHD), 19.7%; hypertensive heart disease (HHD), 16.9%; ischaemic heart disease (IHD), 6.3%; and pericardial disease (PD), 2.1%. Overall direct cost of HF hospitalization was Kshs. 11,470.94 (SD 8,289.57) per patient per day, with the mean length of hospital stay of 10.1 (SD 7.1). RHD incurred the highest costs, Kshs. 15,299.08 (SD 13,196.89) per patient per day, then IHD, Kshs. 12,966.47 (SD 6656.49), and DCM, Kshs.12,268.08 (SD 7,816.12). Cost of medications was the leading driver, β = 0.56 (0.55 – 0.56), followed by inpatient fees, β = 0.27 (0.27 – 0.28) and laboratory investigations, β = 0.19 (0.18 – 0.19).

Cor pulmonale, CM, RHD and HHD were the major causes of HF. The overall direct medical cost of hospitalization was extremely expensive compared with the average monthly household income per capita in Kenya. Widespread insurance cover is therefore recommended to cushion families against such catastrophic health expenditures beside public health measures aimed at addressing primary causes of HF.
Genomic epidemiology and evolution of rhinovirus in western Washington State, 2021-22
Authors: Goya Stephanie , Wendm Seffir T. , Xie Hong , Nguyen Tien V. , Barnes Sarina , Shankar Rohit R. , Sereewit Jaydee , Cruz Kurtis , Pérez-Osorio Ailyn C. , Mills Margaret G. , Greninger Alexander L
Published: February 2024

Background

Human rhinoviruses (RV) primarily cause the common cold, but infection outcomes vary from subclinical to severe cases, including asthma exacerbations and fatal pneumonia in immunocompromised individuals. To date, therapeutic strategies have been hindered by the high diversity of serotypes. Global surveillance efforts have traditionally focused on sequencing VP1 or VP2/VP4 genetic regions, leaving gaps in understanding RV true genomic diversity.

Methods

We sequenced 1,003 RV genomes from nasal swabs of symptomatic and asymptomatic individuals to explore viral evolution during two epidemiologically distinct periods in Washington State: when the COVID-19 pandemic affected the circulation of other seasonal respiratory viruses except for RV (February – July 2021), and when the seasonal viruses reemerged with the severe RSV and influenza outbreak (November-December 2022). We constructed maximum likelihood and BEAST-phylodynamic trees to characterize intra-genotype evolution.

Results

We detected 100 of 168 known genotypes, identified two new genotypes (A111 and C59), and observed inter-genotypic recombination and genotype cluster swapping from 2021 to 2022. We found a significant association between the presence of symptoms and viral load, but not with RV species or genotype. Phylodynamic trees, polyprotein selection pressure, and Shannon diversity revealed co-circulation of divergent clades within genotypes with high amino acid constraints throughout polyprotein.

Discussion

Our study underscores the dynamic nature of RV genomic epidemiology within a localized geographic region, as more than 20% of existing genotypes within each RV species co-circulated each month. Our findings also emphasize the importance of investigating correlations between rhinovirus genotypes and serotypes to understand long-term immunity and cross-protection.
Impact of loss-of-function in angiopoietin-like 4 on the human phenome
Authors: Gagnon Eloi , Bourgault Jérome , Gobeil Émilie , Thériault Sébastien , Arsenault Benoit J.
Published: February 2024

Background

Carriers of the E40K loss-of-function variant in Angiopoietin-like 4 (ANGPTL4), have lower plasma triglyceride levels as well as lower rates of coronary artery disease (CAD) and type 2 diabetes (T2D). These genetic data suggest ANGPTL4 inhibition as a potential therapeutic target for cardiometabolic diseases. However, it is unknown whether the association between E40K and human diseases is due to linkage disequilibrium confounding. The broader impact of genetic ANGPTL4 inhibition is also unknown, raising uncertainties about the safety and validity of this target.

Methods

To assess the impact of ANGPLT4 inhibition, we evaluated the impact of E40K and other loss-of-function variants inANGPTL4on a wide range of health markers and diseases.. The E40K impact was assessed in 29 publicly available genome-wide association meta-analyses of European ancestry on cardiometabolic traits and diseases as well as 1589 diseases assessed in electronic health record within FinnGen (n=309,154). To ensure that these relationships were truly causal, and not driven by other correlated variants, we used the Bayesian fine mapping algorithm CoPheScan.

Results

The CoPheScan posterior probability of E40K being the causal variant for triglyceride was 99.99%, validating the E40K to proxy lifelong lower activity of ANGPTL4. The E40K mutation was associated with lower risk of CAD (odds ratio [OR]=0.84, 95% CI=0.81 to 0.87, p=3.6e-21) and T2D (OR=0.91, 95% CI=0.87 to 0.95, p=2.8e-05) in GWAS meta-analyses, with results replicated in FinnGen. These significant results were also replicated using other rarer loss-of-function variants identified through whole exome sequencing in 488,278 participants of various ancestry in the UK Biobank. Using a Mendelian randomization study design, the E40K variant effect on cardiometabolic diseases was concordant with lipoprotein lipase enhancement (r=0.85), but not hepatic lipaseenhancement (r=-0.10), suggesting that ANGPTL4 effects on cardiometabolic diseases are potentially mainly mediated through lipoprotein lipase. The E40K variant did not significantly increase the risk of any of the 1589 diseases tested in FinnGen.

Conclusion

ANGPTL4 inhibition may represent a potentially safe and effective target for cardiometabolic diseases prevention or treatment.
AMPK-activator ATX-304 reduces oxidative stress and improves MASLD via metabolic switching
Authors: Holm Emanuel , Vermeulen Isabeau , Parween Saba , López-Pérez Ana , Cillero-Pastor Berta , Vandenbosch Michiel , Remeseiro Silvia , Hörnblad Andreas
Published: February 2024

Abstract

Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease worldwide for which there are no approved treatments. Adenosine monophosphate-activated protein kinase (AMPK) is an interesting therapeutical target since it acts as a central regulator of cellular metabolism. Despite efforts to target the AMPK, no direct activators has yet been approved for treatment of this disease. This study investigates the effect of AMPK activator ATX-304 in a preclinical mouse model of progressive fatty liver disease. The data demonstrate that ATX-304 diminishes body fat mass, lowers blood cholesterol levels, mitigates liver steatosis, and ameliorates the development of liver fibrosis. The beneficial effects of ATX-304 treatment are accompanied by a shift in the liver metabolic program, including increased lipid oxidation, reduced lipid synthesis, as well as remodeling of cholesterol and lipid transport. We also observed variations in lipid distribution among liver lobes in response to ATX-304, and a shift in the zonal distribution of lipid droplets upon treatment. Taken together, our data suggest that ATX-304 holds promise as a potential treatment for Metabolically Associated Fatty Liver Disease (MAFLD), including in human patients.
NOTUM-MEDIATED WNT SILENCING DRIVES EXTRAVILLOUS TROPHOBLAST CELL LINEAGE DEVELOPMENT
Authors: Shukla Vinay , Irusta Ayelen Moreno , Varberg Kaela M , Kuna Marija , Iqbal Khursheed , Galligos Anna M , Aplin John D , Choudhury Ruhul H , Okae Hiroaki , Arima Takahiro , Soares Michael J
Published: February 2024

Trophoblast stem (TS) cells have the unique capacity to differentiate into specialized cell types, including extravillous trophoblast (EVT) cells. EVT cells invade into and transform the uterus where they act to remodel the vasculature facilitating the redirection of maternal nutrients to the developing fetus. Disruptions in EVT cell development and function are at the core of pregnancy-related disease. WNT-activated signal transduction is a conserved regulator of morphogenesis of many organ systems, including the placenta. In human TS cells, activation of canonical WNT signaling is critical for maintenance of the TS cell stem state and its downregulation accompanies EVT cell differentiation. We show that aberrant WNT signaling undermines EVT cell differentiation. Notum, palmitoleoyl-protein carboxylesterase (NOTUM), a negative regulator of canonical WNT signaling, was prominently expressed in first trimester EVT cells developing in situ and upregulated in EVT cells derived from human TS cells. Furthermore, NOTUM was required for optimal human TS cell differentiation to EVT cells. Activation of NOTUM in EVT cells is driven, at least in part, by endothelial PAS domain 1 (also called hypoxia-inducible factor 2 alpha). Collectively, our findings indicate that canonical WNT signaling is essential for maintenance of human trophoblast cell stemness and regulation of human TS cell differentiation. Downregulation of canonical WNT signaling via the actions of NOTUM is required for optimal EVT cell differentiation.
Delaying cefiderocol resistance development in NDM-producingEnterobacter cloacaecomplex by combining cefiderocol with aztreonamin vitro
Authors: Göpel Lisa , Tran Nguyen Minh Thu , Tran Thanh Tung , Hauswaldt Susanne , Nur Canbulat Özge , Rupp Jan , Boutin Sébastien , Nurjadi Dennis
Published: February 2024

Background

The rapid development of cefiderocol resistance poses a significant concern, particularly in Enterobacterales that produce New Delhi metallo-β-lactamase (NDM). This study explores the potential of inhibiting the development of cefiderocol resistance by combining cefiderocol with aztreonam.

Methods

A resistance induction experiment using 20 clinical isolates was performed to assess the impact of cefiderocol-aztreonam on preventing cefiderocol resistance development at 4x and 10x cefiderocol MIC, with and without aztreonam (2, 4, 8 µg/ml). Additionally, serial passaging with doubling cefiderocol concentrations was performed with and without aztreonam. Whole genome sequencing (WGS) was performed to identify potential genetic factors associated with the phenotype.

Results

Among the 20E. cloacaecomplex isolates, 40% (8/20) exhibited a significant reduction in cefiderocol MIC (≥4-fold MIC reduction) in the presence of 4 µg/ml aztreonam. Combining cefiderocol with a fixed concentration of 4 µg/ml aztreonam inhibited cefiderocol resistance development in these eight isolates at an inoculum of 107cfu/ml. Additional resistance induction experiments through serial passaging indicated a delayed emergence of cefiderocol-resistant clones when cefiderocol was combined with aztreonam. WGS analysis revealed a significant positive association betweenblaCTX-M-15,blaOXA-1, and other co-localized genes with a substantial MIC reduction for cefiderocol-aztreonam compared to cefiderocol alone.

Conclusion

Our study suggested that cefiderocol resistance development in NDM-producingE. cloacaecomplex can be delayed or inhibited by combining cefiderocol with aztreonam, even in the presence of multiple β-lactamase genes. A MIC reduction of at least 4-fold emerges as the most reliable predictor for inhibiting resistance development with this dual β-lactam combination.
Working memory constraints for visuomotor retrieval strategies
Authors: Velázquez-Vargas Carlos A. , Taylor Jordan A.
Published: February 2024

Recent work has shown the fundamental role that cognitive strategies play in visuomotor adaptation. While algorithmic strategies, such as mental rotation, are flexible and generalizable, they are computationally demanding. To avoid this computational cost, people can instead rely on memory retrieval of previously successful visuomotor solutions. However, such a strategy is likely subject to strict stimulus-response associations and rely heavily on working memory. In a series of five experiments, we sought to estimate the constraints in terms of capacity and precision of working memory retrieval for visuomotor adaptation. This was accomplished by leveraging different variations of visuomotor item-recognition and visuomotor rotation recall tasks where we associated unique rotations with specific targets in the workspace and manipulated the set size (i.e., number of rotation-target associations). Notably, from Experiment 1 to 4, we found key signatures of working memory retrieval and not mental rotation. In particular, participants were less accurate and slower for larger set sizes and less recent items. Using a Bayesian-latent mixture model, we found that such decrease in performance is the result of both an increase in guessing behavior and of less precise samples from memory. In addition we estimated that participants’ working memory capacity was limited to 2-5 items, after which guessing increasingly dominated performance. Finally, in Experiment 5, we showed how the constraints observed across Experiments 1 to 4 can be overcome when relying on long-term memory retrieval. Our results point to the opportunity of studying other sources of memories where visuomotor solutions can be stored (e.g., episodic memories) to achieve successful adaptation.
Atlas for the Lateralized Visuospatial Attention Networks (ALANs): Insights from fMRI and Network Analyses
Authors: Labache Loïc , Petit Laurent , Joliot Marc , Zago Laure
Published: February 2024

Hemispheric specialization is central to human evolution and fundamental to human cognitive abilities. While being a defining feature of functional brain architecture, hemispheric specialization is overlooked to derive brain parcellations. Alongside language, which is typically lateralized in the left hemisphere, visuospatial attention is set to be its counterpart in the opposite hemisphere. However, it remains uncertain to what extent the anatomical and functional underpinnings of lateralized visuospatial attention mirror those supporting language. Building on our previous work, which established a lateralized brain atlas for language, we propose a comprehensive cerebral lateralized atlas delineating the anatomo-functional bases of visuospatial attention, ALANs. Combining task and resting-state functional connectivity analyses, we identified 95 lateralized brain areas comprising five networks supporting visuospatial attention processes. Among them, we can find two large-scale networks: the ParietoFrontal and TemporoFrontal networks. We identify hubs playing a pivotal role in the intra-hemispheric interaction within visuospatial attentional networks. The rightward lateralized ParietoFrontal encompasses one hub, the inferior frontal sulcus, while the TemporoFrontal network encompasses two right hubs: the inferior frontal cortex (pars triangularis and the anterior insula) and the posterior part of the superior temporal sulcus. Together, these networks encompass the homotope of the language network from the left hemisphere. This atlas of visuospatial attention provides valuable insights for future investigations into the variability of visuospatial attention and hemispheric specialization research. Additionally, it facilitates more effective comparisons among different studies, thereby enhancing the robustness and reliability of research in the field of attention.
Scaling Properties for Artificial Neural Network Models of a Small Nervous System
Authors: Simeon Quilee , Venâncio Leandro , Skuhersky Michael A. , Nayebi Aran , Boyden Edward S. , Yang Guangyu Robert
Published: February 2024

The nematode wormC. elegansprovides a unique opportunity for exploringin silicodata-driven models of a whole nervous system, given its transparency and well-characterized nervous system facilitating a wealth of measurement data from wet-lab experiments. This study explores the scaling properties that may govern learning the underlying neural dynamics of this small nervous system by using artificial neural network (ANN) models. We investigate the accuracy of self-supervised next time-step neural activity prediction as a function of data and models. For data scaling, we report a monotonic log-linear reduction in mean-squared error (MSE) as a function of the amount of neural activity data. For model scaling, we find MSE to be a nonlinear function of the size of the ANN models. Furthermore, we observe that the dataset and model size scaling properties are influenced by the particular choice of model architecture but not by the precise experimental source of theC. elegansneural data. Our results fall short of producing long-horizon predictive and generative models ofC. eleganswhole nervous system dynamics but suggest directions to achieve those. In particular our data scaling properties extrapolate that recording more neural activity data is a fruitful near-term approach to obtaining better predictive ANN models of a small nervous system.
Pheromone representation in the ant antennal lobe changes with age
Authors: Hart Taylor , Lopes Lindsey E. , Frank Dominic D. , Kronauer Daniel J.C.
Published: February 2024

While the neural basis of age-related decline has been extensively studied (1–3), less is known about changes in neural function during the pre-senescent stages of adulthood. Adult neural plasticity is likely a key factor in social insect age polyethism, where individuals perform different tasks as they age and divide labor in an age-dependent manner (4–9). Primarily, workers transition from nursing to foraging tasks (5,10), become more aggressive, and more readily display alarm behavior (11–16) as they get older. While it is unknown how these behavioral dynamics are neurally regulated, they could partially be generated by altered salience of behaviorally relevant stimuli (4,6,7). Here, we investigated how odor coding in the antennal lobe (AL) changes with age in the context of alarm pheromone communication in the clonal raider ant (Ooceraea biroi) (17). Similar to other social insects (11,12,16), older ants responded more rapidly to alarm pheromones, the chemical signals for danger. Using whole-AL calcium imaging (18), we then mapped odor representations for five general odorants and two alarm pheromones in young and old ants. Alarm pheromones were represented sparsely at all ages. However, alarm pheromone responses within individual glomeruli changed with age, either increasing or decreasing. Only two glomeruli became sensitized to alarm pheromones with age, while at the same time becoming desensitized to general odorants. Our results suggest that the heightened response to alarm pheromones in older ants occurs via increased sensitivity in these two core glomeruli, illustrating the importance of sensory modulation in social insect division of labor and age-associated behavioral plasticity.
Pathogenic variants inCRXhave distinctcis-regulatory effects on enhancers and silencers in photoreceptors
Authors: Shepherdson James L. , Friedman Ryan Z. , Zheng Yiqiao , Sun Chi , Oh Inez Y. , Granas David M. , Cohen Barak A. , Chen Shiming , White Michael A.
Published: February 2024

Dozens of variants in the gene for the homeodomain transcription factor (TF) cone-rod homeobox (CRX) are linked with human blinding diseases that vary in their severity and age of onset. How different variants in this single TF alter its function in ways that lead to a range of phenotypes is unclear. We characterized the effects of human disease-causing variants on CRXcis-regulatory function by deploying massively parallel reporter assays (MPRAs) in mouse retina explants carrying knock-ins of two variants, one in the DNA-binding domain (p.R90W) and the other in the transcriptional effector domain (p.E168d2). The degree of reporter gene dysregulation in these mutantCrxretinas corresponds with their phenotypic severity. The two variants affect similar sets of enhancers, and p.E168d2 has distinct effects on silencers.Cis-regulatory elements (CREs) near cone photoreceptor genes are enriched for silencers that are derepressed in the presence of p.E168d2. Chromatin environments of CRX-bound loci are partially predictive of episomal MPRA activity, and distal elements whose accessibility increases later in retinal development are enriched for CREs with silencer activity. We identified a set of potentially pleiotropic regulatory elements that convert from silencers to enhancers in retinas that lack a functional CRX effector domain. Our findings show that phenotypically distinct variants in different domains of CRX have partially overlapping effects on itscis-regulatory function, leading to misregulation of similar sets of enhancers while having a qualitatively different impact on silencers.
Preferential formation of Z-RNA over intercalated motifs in long noncoding RNA
Authors: Bhatt Uditi , Cucchiarini Anne , Luo Yu , Evans Cameron W. , Mergny Jean-Louis , Iyer K. Swaminathan , Smith Nicole M.
Published: February 2024

Secondary structure is a principal determinant of lncRNA function, predominantly regarding scaffold formation and interfaces with target molecules. Noncanonical secondary structures that form in nucleic acids have known roles in regulating gene expression and include G-quadruplexes (G4s), intercalated motifs (iMs), and R-loops (RLs). In this paper, we used the computational tools G4-iM Grinder and QmRLFS-finder to predict the formation of each of these structures throughout the lncRNA transcriptome in comparison to protein-coding transcripts. The importance of the predicted structures in lncRNAs in biological contexts was assessed by combining our results with publicly available lncRNA tissue expression data followed by pathway analysis. The formation of predicted G4 (pG4) and iM (piM) structures in select lncRNA sequences was confirmed in vitro using biophysical experiments under near-physiological conditions. We find that the majority of the tested pG4s form highly stable G4 structures, and identify many previously unreported G4s in biologically important lncRNAs. In contrast, none of the piM sequences are able to form iM structures, consistent with the idea that RNA is unable to form stable iMs. Unexpectedly, these C-rich sequences instead form Z-RNA structures, which have not been previously observed in regions containing cytosine repeats and represent an interesting and underexplored target for protein–RNA interactions. Our results highlight the prevalence and potential structure-associated functions of noncanonical secondary structures in lncRNAs, and show G4 and Z-RNA structure formation in many lncRNA sequences for the first time, furthering the understanding of the structure–function relationship in lncRNAs.
Differences in molecular sampling and data processing explain variation among single-cell and single-nucleus RNA-seq experiments
Authors: Chamberlin John T. , Lee Younghee , Marth Gabor T. , Quinlan Aaron R.
Published: February 2024

A mechanistic understanding of the biological and technical factors that impact transcript measurements is essential to designing and analyzing single-cell and single-nucleus RNA sequencing experiments. Nuclei contain the same pre-mRNA population as cells, but they contain a small subset of the mRNAs. Nonetheless, early studies argued that single-nucleus analysis yielded results comparable to cellular samples if pre-mRNA measurements were included. However, typical workflows do not distinguish between pre-mRNA and mRNA when estimating gene expression, and variation in their relative abundances across cell types has received limited attention. These gaps are especially important given that incorporating pre-mRNA has become commonplace for both assays, despite known gene length bias in pre-mRNA capture. Here, we reanalyze public data sets from mouse and human to describe the mechanisms and contrasting effects of mRNA and pre-mRNA sampling on gene expression and marker gene selection in single-cell and single-nucleus RNA-seq. We show that pre-mRNA levels vary considerably among cell types, which mediates the degree of gene length bias and limits the generalizability of a recently published normalization method intended to correct for this bias. As an alternative, we repurpose an existing post hoc gene length–based correction method from conventional RNA-seq gene set enrichment analysis. Finally, we show that inclusion of pre-mRNA in bioinformatic processing can impart a larger effect than assay choice itself, which is pivotal to the effective reuse of existing data. These analyses advance our understanding of the sources of variation in single-cell and single-nucleus RNA-seq experiments and provide useful guidance for future studies.
Pangenome-genotyped structural variation improves molecular phenotype mapping in cattle
Authors: Leonard Alexander S. , Mapel Xena M. , Pausch Hubert
Published: February 2024

Expression and splicing quantitative trait loci (e/sQTL) are large contributors to phenotypic variability. Achieving sufficient statistical power for e/sQTL mapping requires large cohorts with both genotypes and molecular phenotypes, and so, the genomic variation is often called from short-read alignments, which are unable to comprehensively resolve structural variation. Here we build a pangenome from 16 HiFi haplotype-resolved cattle assemblies to identify small and structural variation and genotype them with PanGenie in 307 short-read samples. We find high (>90%) concordance of PanGenie-genotyped and DeepVariant-called small variation and confidently genotype close to 21 million small and 43,000 structural variants in the larger population. We validate 85% of these structural variants (with MAF > 0.1) directly with a subset of 25 short-read samples that also have medium coverage HiFi reads. We then conduct e/sQTL mapping with this comprehensive variant set in a subset of 117 cattle that have testis transcriptome data, and find 92 structural variants as causal candidates for eQTL and 73 for sQTL. We find that roughly half of the top associated structural variants affecting expression or splicing are transposable elements, such as SV-eQTL forSTN1andMYH7and SV-sQTL forCEP89andASAH2. Extensive linkage disequilibrium between small and structural variation results in only 28 additional eQTL and 17 sQTL discovered when including SVs, although many top associated SVs are compelling candidates.
Vortex solutions in a binary immiscible Bose-Einstein condensate
Authors: Doran R. , Baggaley A. W. , Parker N. G.
Published: February 2024

We consider the mean-field vortex solutions and their stability within a two-component Bose-Einstein condensate in the immiscible limit. A variational approach is employed to study a system consisting of a majority component which contains a single quantized vortex and a minority component which fills the vortex core. We show that a super-Gaussian function is a good approximation of the two-component vortex solution for a range of atom numbers of the infilling component by comparing the variational solutions to the full numerical solutions of the coupled Gross-Pitaevskii equations. We subsequently examine the stability of the vortex solutions by perturbing the infilling component away from the center of the vortex core, thereby demonstrating their stability to small perturbations. Finally, we consider the dynamics of infilled vortices.

Published by the American Physical Society
2024
Genus drop in hyperelliptic Feynman integrals
Authors: Marzucca Robin , McLeod Andrew J. , Page Ben , Pögel Sebastian , Weinzierl Stefan
Published: February 2024

The maximal cut of the nonplanar crossed box diagram with all massive internal propagators was long ago shown to encode a hyperelliptic curve of genus 3 in momentum space. Surprisingly, in Baikov representation, the maximal cut of this diagram only gives rise to a hyperelliptic curve of genus 2. To show that these two representations are in agreement, we identify a hidden involution symmetry that is satisfied by the genus 3 curve, which allows it to be algebraically mapped to the curve of genus 2. We then argue that this is just the first example of a general mechanism by means of which hyperelliptic curves in Feynman integrals can drop from genus g to ⌈g/2⌉ or ⌊g/2⌋. We find an algorithm to test for the presence of genus drop, and highlight further instances of this mechanism in Feynman integrals.

Published by the American Physical Society
2024
Aberration-driven tilted emission in degenerate cavities
Authors: Gurevich S. V. , Maucher F. , Javaloyes J.
Published: February 2024

The compensation of chromatic dispersion opened new avenues and extended the level of control upon pattern formation in the . In this paper, we propose the use of a nearly degenerate laser cavity as a general framework allowing for the exploration of higher contributions to diffraction in the domain. Our approach leverages the interplay between optical aberrations and the proximity to the self-imaging condition, which allows us to cancel or reverse paraxial diffraction. As an example, we show how spherical aberrations materialize into a transverse bi-Laplacian operator and, thereby, explain the stabilization of temporal solitons traveling off-axis in an unstable mode-locked broad-area surface-emitting laser. We disclose an analogy between these regimes and the dynamics of a quantum particle in a double-well potential.

Published by the American Physical Society
2024
Stability of
PT
and anti-
PT
-symmetric Hamiltonians with multiple harmonics
Authors: Cen Julia , Joglekar Yogesh N. , Saxena Avadh
Published: February 2024

Hermitian Hamiltonians with time-periodic coefficients can be analyzed via Floquet theory, and have been extensively used for engineering Floquet Hamiltonians in standard quantum simulators. Generalized to non-Hermitian Hamiltonians, time periodicity offers avenues to engineer the landscape of Floquet quasienergies across the complex plane. We investigate two-level non-Hermitian PT and anti-PT-symmetric Hamiltonians with coefficients that have multiple harmonics using Floquet theory. By analytical and numerical calculations, we obtain their regions of stability, defined by real Floquet quasienergies, and contours of exceptional point (EP) degeneracies. We extend our analysis to study the phases that accompany these cyclic changes with the biorthogonality approach. Our results demonstrate that these time-periodic Hamiltonians generate a rich landscape of stable (real) and unstable (complex) regions.

Published by the American Physical Society
2024
Interacting random-field dipole defect model for heating in semiconductor-based qubit devices
Authors: Choi Yujun , Joynt Robert
Published: February 2024

Semiconductor qubit devices suffer from the drift of important device parameters as they are operated. The most important example is a shift in qubit operating frequencies. This effect appears to be directly related to the heating of the system as gate operations are applied. We show that the main features of this phenomenon can be explained by the two-level systems that can also produce charge noise if these systems are considered to form an interacting random-field glass. The most striking feature of the theory is that the frequency shift can be nonmonotonic in temperature. The success of the theory and the questions it raises considerably narrow the possible models for the two-level systems.

Published by the American Physical Society
2024
Study on the structure and corrosion resistance of MoS2/MgO micro-arc oxidation composite ceramic coating on the surface of ZK60 magnesium alloy
Authors: Chen Xiaowen , Xie Wanlin , Tang Song , Zhang Meng , Song Hao , Ran Qingzheng , Zhang Defen
Published: February 2024

Purpose

The purpose of this study is to examine the impact of MoS2 on the microstructure and characteristics of micro-arc oxidized (MAO) ceramic coatings created on ZK60 magnesium alloy through the addition of varying concentrations of MoS2 particles to the electrolyte, aiming to enhance the corrosion resistance of magnesium alloy.

Design/methodology/approach

The surface morphology, roughness and phase composition of the coatings were analyzed using scanning electron microscopy, a hand-held roughness tester and an X-ray diffractometer, respectively, and the corrosion resistance of the MAO coatings prepared by the addition of different contents of MoS2 particles was tested and analyzed using an electrochemical workstation.

Findings

The results demonstrate that MoS2/MgO composite coatings have been successfully prepared on the surface of magnesium alloys through micro-arc oxidation. Furthermore, the corrosion resistance of the ZK60 magnesium alloy prepared with the addition of 1.0 g/L MoS2 was the best compared to the other samples.

Originality/value

MoS2 particles were able to penetrate the coatings successfully during the micro-arc oxidation process, acting as a barrier in the micropores to prevent the corrosion medium from touching the surface, thus improving the corrosion resistance of the sample. The electrochemical workstation was used to study the corrosion resistance of the MoS2/MAO coating on the ZK60 magnesium alloy.
Measuring systemic risk in China: a textual analysis
Authors: Ma Wenbo , Li Kai , Pan Wei-Fong , Wang Xinjie
Published: February 2024

Purpose

The purpose of this paper is to construct an index for systemic risk in China.

Design/methodology/approach

This paper develops a systemic risk index for China (SRIC) using textual information from 26 leading newspapers in China. Our index measures the systematic risk from 21 topics relating to China’s economy and provides narratives of the sources of systemic risk.

Findings

SRIC effectively predicts changes in GDP, aggregate financing to the real economy and the purchasing managers’ index. Moreover, SRIC explains several other commonly used macroeconomic indicators. Our risk measure provides a helpful monitoring tool for policymakers to manage systemic risk.

Originality/value

The paper construct an index of systemic risk based on the information extracted from newspaper articles. This approach is new to the literature.
Teachers’ affective and physical well-being: emotional intelligence, emotional labour and implications for leadership
Authors: Karakus Mehmet , Toprak Mustafa , Caliskan Omer , Crawford Megan
Published: February 2024

Purpose

This study aims to examine the role of teachers’ emotional intelligence (EI) and emotional labour (EL) strategies in their affective and physical well-being.

Design/methodology/approach

The quantitative data were collected from 436 primary school teachers. Likert-type scales were used to measure the variables. Confirmatory factor analyses were performed for the construct validity of the scales, and path analysis was used to test the hypothesised model.

Findings

The final structural equation model suggests that teachers' EI levels and display of appropriate EL strategies significantly reduce their stress, anxiety, burnout and psychosomatic complaints (PSCs). The final model shows that the deep acting strategy, which includes more adaptive emotion regulation strategies, improves teachers’ affective and physical well-being, while the surface acting strategy has a detrimental effect on their well-being.

Originality/value

To the best of the authors’ knowledge, this study is the first in the literature to highlight the importance of school teachers’ EI and EL strategies in managing stress, anxiety, burnout (affective well-being),and alleviating PSCs (physical well-being) within a single structural equation model. The findings have implications for educational leaders in fostering teachers’ emotional competencies and resources.
Principles and practices of modular course design in higher engineering education
Authors: Mesutoglu Canan , Stollman Saskia , Lopez Arteaga Ines
Published: February 2024

Purpose

Few resources exist to incorporate principles of modular approach to course design. This research aimed to help instructors by presenting principles for practical and empirically informed modular course design in engineering education.

Design/methodology/approach

In the first phase, a systematic literature review was completed to identify categories addressing a modular course design. Search and screening procedures resulted in 33 qualifying articles describing the development of a modular course. In the second phase, 6 expert interviews were conducted to elaborate on the identified categories.

Findings

Guided by the interview results and the ADDIE (Analyze, Design, Develop, Implement, and Evaluate) course design model, the categories were compiled into six design principles. To present the design principles in relation to the guiding principles of modular approach, an overarching conceptual model was developed.

Originality/value

Here, we present our innovation; a foundation for an evidence-based systematic approach to modular course design. Implications have value for supporting flexibility and autonomy in learning.