bluuebunny/crossref_metadata_2025 huggingface dataset:
Why the adventitious roots of poplar are so colorful: RNAseq and metabolomic analysis reveal flavonols, flavones, and anthocyanins accumulation in canker pathogens-induced adventitious roots in poplar
Authors: Min Li , Yuchen Fu , Jinxin Li , Wanna Shen , Li Wang , Zheng Li , Shiqi Zhang , Huixiang Liu , Xiaohua Su , Jiaping Zhao
Published: March 2024

Recently, we observed a novel allometry on poplar stems, with copious colorful adventitious roots (ARs) induced by fungal canker pathogens. Here, we reveal chemical, physiological, and molecular mechanisms of AR coloration in a poplar-pathogen (Valsa sordida/Botrosphaeria dothidea) interaction system using our phloem girdling-inoculation system. Light-induced coloration in ARs: red/rosy under sunlight and milky white under shading. Chemical and metabolomic analyses indicated that numerous (93 in all 110) and high relative intensities/contents of flavonoids metabolites (mainly including flavonols, flavones, and anthocyanins class) accumulate in red ARs, some flavones and anthocyanins metabolites all contribute to the color of poplar ARs, and cyanidin-3-O-glucoside is the most abundant colorant. Integrated analysis of metabolomic and transcriptomic analysis suggested that sunlight exposure redirected metabolomic flux from the flavonoid biosynthesis pathway to the flavonols and flavones branch pathways, induced by the upregulation of FLS (flavonol synthase/flavanone 3-hydroxylase) and other structural genes. The anthocyanins metabolomic analysis and the downregulation of the ANS (anthocyanin synthase) gene illustrated a retard of metabolomic flux from leucoanthocyanidins to anthocyanidins; meanwhile, metabolomic results and the upregulation of gene BZ1 (Bronze 1, anthocyanin 3-O-glucosyltransferase) illustrated that sunlight triggered a rapid biosynthesis of anthocyanin metabolites in poplar ARs, which based on the substrate level of anthocyanidins. Transcriptomic and RT-qPCR analyses showed that transcriptional factor MYB113, HY5 (ELONGATED HYPOCOTYL5), and COP1 (Ring-finger protein CONSTITUTIVE PHOTOMORPHOGENIC1) genes positively regulate the expression of the flavonoid/anthocyanin biosynthesis structural genes (such as genes encoding BZ1, FLS, LAR, etc.) in both sunlight-exposed red ARs and white ARs after light exposure, suggesting sunlight induces anthocyanins biosynthesis through the interaction between “MBW” complex and COP1-HY5 module. Moreover, results also showed that 1 SPL gene (squamosa promoter-binding-like protein gene, target of miR156), one component of miR156-SPL module, downregulated in sunlight-exposed poplar ARs, implying the biosynthesis flavonoid/anthocyanin be regulated at the posttranscriptional level. Additionally, this study provides a potential AR experimental system for research on flavonoid/anthocyanin biosynthesis in tree species.
Unravelling the Transcriptomic Symphony of Sarcopenia: Key Pathways and Hub Genes Altered by Muscle Ageing and Caloric Restriction Revealed by RNA Sequencing
Authors: Altab Gulam , Merry Brian J. , Beckett Charles W. , Raina Priyanka , Lopes Inês , Goljanek-Whysall Katarzyna , de Magalhães João Pedro
Published: March 2024

Sarcopenia is a disease involving extensive loss of muscle mass and strength with age and is a major cause of disability and accidents in the elderly. Mechanisms purported to be involved in muscle ageing and sarcopenia are numerous but poorly understood, necessitating deeper study. Hence, we employed high-throughput RNA sequencing to explicate the global changes in protein-coding gene expression occurring in skeletal muscle with age. Caloric restriction (CR) is a proven prophylactic intervention against sarcopenia. Therefore, total RNA was isolated from the muscle tissue of both rats fed ad libitum and CR rats. Collected data were subjected to Gene Ontology, pathway, co-expression, and interaction network analyses. This revealed the functional pathways most activated by both ageing and CR, as well as the key “hub” proteins involved in their activation.

RNA-seq revealed 442 protein-coding genes to be upregulated and 377 to be downregulated in aged muscle, compared to young muscle. Upregulated genes were commonly involved in protein folding and the immune response; meanwhile, downregulated genes were often related to developmental biology. CR was found to suppress 69.7% and rescue 57.8% of the genes found to be upregulated and downregulated in aged muscle, respectively. In addition, CR uniquely upregulated 291 and downregulated 304 protein-coding genes. Hub genes implicated in both ageing and CR includedGc,Plg,Irf7,Ifit3,Usp18,Rsad2,BlmandRT1-A2, whilst those exclusively implicated in CR responses includedAlb,Apoa1,Ambp,F2,Apoh,Orm1,Mx1,Oasl2andRtp4. Hub genes involved in ageing but unaffected by CR includedFgg,Fga,FgbandSerpinc1. In conclusion, this comprehensive RNA sequencing study highlighted gene expression patterns, hub genes and signalling pathways most affected by ageing in skeletal muscle. This data may provide the initial evidence for several targets for therapeutic interventions against sarcopenia.
Physiological correlates of a simple saccadic-decision task to extended objects in superior colliculus
Authors: Caziot B. , Cooper B. , Harwood M. R. , McPeek R. M.
Published: March 2024

Our vision is best only in the center of our gaze, and we use saccadic eye movements to direct gaze to objects and features of interest. We make more than 180,000 saccades per day, and accurate and efficient saccades are crucial for most visuo-motor tasks. Saccades are typically studied using small point stimuli, despite the fact that most real-world visual scenes are composed of extended objects. Recent studies in humans have shown that the initiation latency of saccades is strongly dependent on the size of the target (the “size-latency effect”), perhaps reflecting a tradeoff between the cost of making a saccade to a target and the expected information gain that would result. Here, we investigate the neuronal correlates of the size-latency effect in the macaque superior colliculus. We analyzed the latency variations of saccades to different size targets within a stochastic accumulator model framework. The model predicted a steeper increase in activity for smaller targets compared to larger ones. Surprisingly, the model also predicted an increase in saccade initiation threshold for larger targets. We found that the activity of intermediate-layer SC visuomotor neurons is in close agreement with the model predictions. We also found evidence that these effects may be a consequence of the visual responses of SC neurons to targets of different sizes. These results shed new light on the sources of delay within the saccadic system, a system that we heavily depend upon in the performance of most visuo-motor tasks.
Social ageing can protect against infectious disease in a group-living primate
Authors: Siracusa Erin R. , Pavez-Fox Melissa A. , Negron-Del Valle Josué E. , Phillips Daniel , Platt Michael L. , Snyder-Mackler Noah , Higham James P. , Brent Lauren J. N. , Silk Matthew J.
Published: March 2024

The benefits of social living are well established, but sociality also comes with costs, including infectious disease risk. This cost-benefit ratio of sociality is expected to change across individuals’ lifespans, which may drive changes in social behaviour with age. To explore this idea, we combine data from a group-living primate for which social ageing has been described with epidemiological models to show that having lower social connectedness when older can protect against the costs of a hypothetical, directly transmitted endemic pathogen. Assuming no age differences in epidemiological characteristics (susceptibility to, severity, and duration of infection), older individuals suffered lower infection costs, which was explained largely because they were less connected in their social networks than younger individuals. This benefit of ‘social ageing’ depended on epidemiological characteristics and was greatest when infection severity increased with age. When infection duration increased with age, social ageing was beneficial only when pathogen transmissibility was low. Older individuals benefited most from having a lower frequency of interactions (strength) and network embeddedness (closeness) and benefited less from having fewer social partners (degree). Our study provides a first examination of the epidemiology of social ageing, demonstrating the potential for pathogens to influence evolutionary dynamics of social ageing in natural populations.
Three-dimensional spatio-angular fluorescence microscopy with a polarized dual-view inverted selective-plane illumination microscope (pol-diSPIM)
Authors: Chandler Talon , Guo Min , Su Yijun , Chen Jiji , Wu Yicong , Liu Junyu , Agashe Atharva , Fischer Robert S. , Mehta Shalin B. , Kumar Abhishek , Baskin Tobias I. , Jamouille Valentin , Liu Huafeng , Swaminathan Vinay , Nain Amrinder , Oldenbourg Rudolf , La Riviere Patrick , Shroff Hari
Published: March 2024

Polarized fluorescence microscopy is a valuable tool for measuring molecular orientations, but techniques for recovering three-dimensional orientations and positions of fluorescent ensembles are limited. We report a polarized dual-view light-sheet system for determining the three-dimensional orientations and diffraction-limited positions of ensembles of fluorescent dipoles that label biological structures, and we share a set of visualization, histogram, and profiling tools for interpreting these positions and orientations. We model our samples, their excitation, and their detection using coarse-grained representations we call orientation distribution functions (ODFs). We apply ODFs to create physics-informed models of image formation with spatio-angular point-spread and transfer functions. We use theory and experiment to conclude that light-sheet tilting is a necessary part of our design for recovering all three-dimensional orientations. We use our system to extend known two-dimensional results to three dimensions in FM1-43-labelled giant unilamellar vesicles, fast-scarlet-labelled cellulose in xylem cells, and phalloidin-labelled actin in U2OS cells. Additionally, we observe phalloidin-labelled actin in mouse fibroblasts grown on grids of labelled nanowires and identify correlations between local actin alignment and global cell-scale orientation, indicating cellular coordination across length scales.
Drumming Performance and Underlying Muscle Activities in a Professional Rock Drummer with Lower-Limb Dystonia: A Case Study
Authors: Honda Kazuaki , Sata Shizuka , Komine Mizuki , Yamaguchi Satoshi , Kim SungHyek , Kashino Makio , Fujii Shinya
Published: March 2024

Task-specific focal dystonia (TSFD), characterized by the loss of fine motor control and coordination, affects drummers’ lower-limb movements, yet it remains relatively understudied, leaving a gap in understanding its effects on drumming performance and underlying muscle activities. This study explores lower limb dystonia’s impact on drumming performance and underlying muscle activity in a professional rock drummer. The drummer executed an eight-beat pattern on a drum kit, emphasizing kicking the bass drum on the initial beat and performing syncopation of the third beat. Dystonia symptoms primarily manifested in the initial beat, with fewer symptoms on syncopation of the third beat. Analysis revealed decreased bass-drum sound peak amplitude during the initial beat and increased (becoming more negative) synchronization error. Electromyographic (EMG) measurements of ten muscles in the affected right lower limb showed significant changes in the Biceps Femoris (BF), Tibialis Anterior (TA), Extensor Digitorum Longus (EDL), and Extensor Digitorum Brevis (EDB) muscles during symptom onset. Notably, we observed 1) earlier overactivation of the TA and EDL muscles during the leg lift-up motion or preparatory phase of pedaling, 2) reduced activation of the EDB muscle, and 3) increased activation of the BF muscle during the final pedaling movement when symptoms occurred. These findings suggest that lower-limb dystonia symptoms are characterized by a reduction in amplitude and an increase in synchronization error, potentially due to premature overactivation of the ankle dorsiflexor muscles.
BET inhibitors as a therapeutic intervention in gastrointestinal gene signature-positive castration-resistant prostate cancer
Authors: Shukla Shipra , Li Dan , Nguyen Holly , Conner Jennifer , Bayshtok Gabriella , Cho Woo Hyun , Pachai Mohini , Teri Nicholas , Campeau Eric , Attwell Sarah , Trojer Patrick , Ostrovnaya Irina , Gopalan Anuradha , Corey Eva , Chi Ping , Chen Yu
Published: March 2024

A subgroup of castration-resistant prostate cancer (CRPC) aberrantly expresses a gastrointestinal (GI) transcriptome governed by two GI-lineage-restricted transcription factors, HNF1A and HNF4G. In this study, we found that expression of GI transcriptome in CRPC correlates with adverse clinical outcomes to androgen receptor signaling inhibitor treatment and shorter overall survival. Bromo- and extra-terminal domain inhibitors (BETi) downregulated HNF1A, HNF4G, and the GI transcriptome in multiple CRPC models, including cell lines, patient-derived organoids, and patient-derived xenografts, while AR and the androgen-dependent transcriptome were largely spared. Accordingly, BETi selectively inhibited growth of GI transcriptome-positive preclinical models of prostate cancer. Mechanistically, BETi inhibited BRD4 binding at enhancers globally, including both AR and HNF4G bound enhancers while gene expression was selectively perturbed. Restoration of HNF4G expression in the presence of BETi rescued target gene expression without rescuing BRD4 binding. This suggests that inhibition of master transcription factors expression underlies the selective transcriptional effects of BETi.

SIGNIFICANCE

GI transcriptome expression in CRPC is regulated by the HNF1A-HNF4G-BRD4 axis and correlates with worse clinical outcomes. Accordingly, BET inhibitors significantly reduce tumor cell growth in multiple GI-transcriptome-positive preclinical models of CRPC. Our studies point that expression of GI transcriptome could serve as a predictive biomarker to BETi therapy response.
Navigated range expansion promotes migratory culling
Authors: Zhang Yi , Hu Qingjuan , Su Yingtong , Chu Pan , Wei Ting , Li Xuefei , Liu Chenli , Fu Xiongfei
Published: March 2024

Motile organisms can expand into new territories and increase their fitness, while nonmotile viruses usually depend on host migration to spread across long distances. In general, faster host motility facilitates virus transmission. However, recent ecological studies have also shown that animal host migration can reduce viral prevalence by removing infected individuals from the migratory group. Here, we use a bacteria-bacteriophage co-propagation system to investigate how host motility affects viral spread during range expansion. We find that phage spread during chemotaxis-driven navigated range expansion decreases as bacterial migration speed increases. Theoretical and experimental analyses show that the navigated migration leads to a spatial sorting of infected and uninfected hosts in the co-propagating front of bacteria-bacteriophage, with implications for the number of cells left behind. The preferential loss of infected cells in the co-propagating front inhibits viral spread. Further increase in host migration speed leads to a phase transition that eliminates the phage completely. These results illustrate that navigated range expansion of the host can promote the migratory culling of infectious diseases in the migration group.

Significance Statement

Host migration is commonly believed to accelerate the spread of infectious diseases. However, recent ecological studies suggest that migration may impede this spread. In our study, we developed a synthetic host-virus co-propagation model to explore the impact of host range expansion on the interplay between host mobility and virus spatial distribution. Our experimental and theoretical analysis revealed the spatial sorting of uninfected and infected hosts in the navigated propagating front leads to faster back diffusion of infected hosts. This self-organized structure allowed the migrating host population to eradicate the infectious disease, independent of intricate host-virus dynamics.
Clinical multi-omics reveals the role of Tuomin Zhiti Decoction Intervention in Allergic Rhinitis from the perspective of biological network
Authors: Zhao Weibo , Wang Boyang , Kong Lingyao , Wang Qi , Li Shao
Published: March 2024

Background

Increasing evidence showed that seasonal allergic rhinitis (SAR), as an allergy disease, could be alleviated with traditional Chinese medicine (TCM) formula, one example being Tuomin Zhiti Decoction (TZD). However, as a complex composition of TCM herbs, the mechanism of TZD in the treatment of SAR remain unclear.

Purpose

Uncover the mechanism of TZD for treating SAR based on computational analysis and clinical multi-omics experiments.

Study design

Integrate computational analysis including network target analysis and machine learning algorithms with clinical multi-omics experiments and public omics data.

Methods

By analyzing TZD’s composition through a network-based method, we identified the biological effects of each compound, constructing a comprehensive biological network to elucidate TZD’s molecular and pathway mechanisms against AR. Single-arm clinical trials on the gut microbiome and serum transcriptomics corroborated our computational insights. Further validation through public omics data highlighted key TZD compounds, paving the way for future research.

Results

TZD was discovered to exert a regulatory effect on various modules associated with AR, as demonstrated by the constructed biological network. Insights from gut microbiome and serum transcriptomics in clinical trials, where immune-related microbiomes represented by Prevotella, as well as pathways and biological processes including antigen processing and presentation, activation and regulating immune cell surface receptor, were markedly enriched (Pvalue < 0.05), indicated that TZD played a pivotal role in modulating immune processes and the immune cells against AR. With the verification of multi-omics, it was determined that TZD potentially influences immune responses and downstream immune cells like CD4+ T cells, through both direct mechanisms involving antigen and indirect mechanisms mediated by gut microbiomes in the treatment of AR.

Conclusion

Through combination of computational prediction and analysis together with clinical multi-omics, a network target based framework provided a new insight for uncovering the mechanism of TZD for treating AR.
Associations Between Air Pollution and relative Leukocyte Telomere Length Among Northern Swedish Adults: Insights from the Betula Study
Authors: Raza Wasif , Pudas Sara , Kanninen Katja M. , Flanagan Erin , Degerman Sofie , Adolfsson Rolf , Giugno Rosalba , Topinka Jan , Zeng Xiao-wen , Oudin Anna
Published: March 2024

Air pollution is increasingly discussed as a risk factor for dementia, but the biological mechanisms are not yet fully understood. Cellular integrity markers like telomere length are relevant to investigate in relation to air pollution exposure in this context, as they are associated with aging and dementia. Previous studies on air pollution and telomere length have somewhat mixed results, which may partly be due to differences in air pollution modelling, composition, and concentrations. The study aimed to investigate the relationship between source-specific air pollution exposure and telomere length in a low-level air pollution area.

Data were obtained from the Betula project, a longitudinal study in Northern Sweden dedicated to studying aging, memory and dementia. A total of 519 participants who were recruited between 1988 and 1995 were included, whose relative telomere length was measured, and who were followed-up with respect to dementia for more than 20 years. To estimate annual mean air pollution concentrations, a dispersion model linked to each participant’s residential address was employed. We conducted linear regression to explore the associations between annual mean air pollution concentrations at participants’ residences and relative leukocyte telomere length.

In the whole sample, there was no support for air pollution to affect telomere length, with regression slope estimates close to zero and p-values >0.10. There were tendencies for a positive association of longer telomere length and higher exposure to air pollution among individuals who were later diagnosed with dementia (N = 74), but these findings were not conclusive (p-values >0.10). The findings raise questions about susceptibility to air pollution and the state of the inflammatory response in individuals who later will develop dementia. Given the imprecise nature of these estimates, caution is advised in their interpretation however, and validation in other studies is essential.
Autoimmune antibody-induced neuronal hyperactivity triggers pathological Tau in IgLON5 disease
Authors: Askin Bilge , Gómez César Cordero , Duong Sophie Lan-Linh , Kilic Cagla , Goihl Alexander , Newman Andrew , Wagner Jessica , Thomas Valentine , Lamberty Janne , Huebschmann Sabrina , Semenova Ekaterina , Körtvelyessy Peter , Reinhold Dirk , Kornau Hans-Christian , Turko Paul , Neher Jonas J. , Schmitz Dietmar , Rost Benjamin R. , Diez Lisa , Prüss Harald , Wegmann Susanne
Published: March 2024

Anti-IgLON5 disease is an autoimmunity/neurodegeneration overlap disorder in which autoantibodies (AABs) against the neuronal cell surface protein IgLON5 lead to profound brain dysfunction. Brains of patients show Tau pathology, neuroinflammation, and neurodegeneration in multiple brain regions. Through administering patient-derived α-IgLON5 AABs to mice and cultured neurons, we here deciphered the cellular mechanisms of Tau pathology and neurodegeneration in α-IgLON5 disease, highlighting a central role of neuronal activity modulation in the disease pathology. Pathogenic human α-IgLON5 AABs induced acute neuronal hyperactivity, which triggered Tau changes typically found early in Tau-related neurodegenerative diseases like Alzheimer’s disease (AD). α-IgLON5 AAB-induced Tau phosphorylation and somatodendritic resorting selectively occurred in key hippocampal connections, involving dentate gyrus granule cells, mossy fiber projections and commissural fiber tracts. These changes were accompanied by a Tau-specific neuroinflammatory response, involving the complement pathway, microglial MHC class II proteins, T cell receptors, and deregulation of synaptic activity and cell-cell interactions. These findings provide new insights into the origin of autoimmune-triggered α-IgLON5 disease pathology and highlight that, similar to recent reports in AD patients, neuronal hyperactivity may be a disease-overarching driver of Tau pathology.
Interplay of actin nematodynamics and anisotropic tension controls endothelial mechanics
Authors: Dessalles Claire A. , Cuny Nicolas , Boutillon Arthur , Salipante Paul F. , Babataheri Avin , Barakat Abdul I. , Salbreux Guillaume
Published: March 2024

Blood vessels expand and contract actively, while continuously experiencing dynamic external stresses from the blood flow. The mechanical response of the vessel wall is that of a composite material: its mechanical properties depend on a diverse set of cellular mechanical components, which change dynamically as cells respond to external stress. Mapping the relationship between these underlying cellular processes and emergent tissue mechanics is an on-going challenge, in particular in endothelial cells. Here we use a microstretcher mimicking the native environment of blood vessels to assess both the mechanics and cellular dynamics of an endothelial tube in response to a physiological increase in luminal pressure. The characterization of the instantaneous monolayer elasticity reveals a strain-stiffening, actin-dependent and substrate-responsive behavior. In response to a maintained pressure increase, the tissue displays a fluid-like expansion, accompanied by the reorientation of cell shape and of actin fibers. This actin-driven reorientation depends on focal adhesions and adherens junctions, two key mechanosensors. We introduce a mechanical model coupling actin fiber nematodynamics with active and elastic tension generation by actin fibers in the endothelium, which recapitulates the response to pressure of endothelial tubes.
Ongoing hybridisation among clownfishes: the genomic architecture of the Kimbe Bay hybrid zone
Authors: Schmid Sarah , Hartasánchez Diego A. , Gainsford Ashton , Jones Geoffrey P. , Salamin Nicolas
Published: March 2024

Hybrid zones – locations where genetically distinct lineages interact and reproduce – are remarkable resources for exploring the evolutionary trajectory of species. Not only can we learn from hybrid zones about the mechanisms of speciation and how reproductive isolation is maintained, but we can also study their impact on evolutionary processes. Thanks to the advent of next-generation sequencing, we are now able to gain new insight into the structure of hybrid genomes and the factors influencing the outcome of hybridisation. Here, we focus on the Kimbe Bay hybrid zone, a narrow region in the Pacific Ocean where two species of clownfish –Amphiprion chrysopterusandA. sandaracinos– hybridise and give rise to the hybridA. leucokranos. Based on whole-genome sequencing, we found that the hybrid zone is mainly composed of first-generation hybrids, the first evidence of F2 hybrids in the wild and early backcrosses withA. sandaracinos. The recurrent backcrossing with one of the parental species might lead to adaptive introgression, with few adaptive introgressed loci fromA. chrysopterusintegrated into theA. sandaracinosgenomic background. This study builds upon the growing literature body relative to the evolutionary outcomes of hybridisation and its importance in the evolution of many species.
A Mixed Effect Similarity Matrix Regression Model (SMRmix) for Integrating Multiple Microbiome Datasets at Community Level
Authors: He Mengyu , Zhao Ni
Published: March 2024

Background

Recent studies have highlighted the importance of human microbiota in our health and diseases. However, in many areas of research, individual microbiome studies often offer inconsistent results due to the limited sample sizes and the heterogeneity in study populations and experimental procedures. This inconsistency underscores the necessity for integrative analysis of multiple microbiome datasets. Despite the critical need, statistical methods that incorporate multiple microbiome datasets and account for the study heterogeneity are not available in the literature.

Methods

In this paper, we develop a mixed effect similarity matrix regression (SMRmix) approach for identifying community level microbiome shifts between outcomes. SMRmix has a close connection with the microbiome kernel association test, one of the most popular approaches for such a task but is only applicable when we have a single study. SMRmix enables researchers to consolidate findings from diverse microbiome studies.

Results

Via extensive simulations, we show that SMRmix has well-controlled type I error and higher power than some potential competitors. We applied the SMRmix to two real-world datasets. The first, from the HIV-reanalysis consortium, integrated data from 17 studies on gut dysbiosis in HIV. Our analysis confirmed consistent associations between the gut microbiome and HIV infection as well as MSM (men who have sex with men) status, demonstrating greater power than competing methods. The second dataset involved 11 studies on the gut microbiome in colorectal cancer; analysis with SMRmix confirmed significant dysbiosis in affected individuals compared to healthy controls.

Conclusion

The development of SMRmix enables the integration of multiple studies and effectively managing study heterogeneity, and provides a powerful tool for uncovering consistent associations between diseases and community-level microbiome data.
Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer’s Disease fly models
Authors: Park Ye-Jin , Lu Tzu-Chiao , Jackson Tyler , Goodman Lindsey D. , Ran Lindsey , Chen Jiaye , Liang Chung-Yi , Harrison Erin , Ko Christina , Hsu Ao-Lin , Yamamoto Shinya , Qi Yanyan , Bellen Hugo J. , Li Hongjie
Published: March 2024

Peripheral tissues become disrupted in Alzheimer’s Disease (AD). However, a comprehensive understanding of how the expression of AD-associated toxic proteins, Aβ42 and Tau, in neurons impacts the periphery is lacking. UsingDrosophila, a prime model organism for studying aging and neurodegeneration, we generated the Alzheimer’s Disease Fly Cell Atlas (AD-FCA): whole-organism single-nucleus transcriptomes of 219 cell types from adult flies neuronally expressing human Aβ42 or Tau. In-depth analyses and functional data reveal impacts on peripheral sensory neurons by Aβ42 and on various non-neuronal peripheral tissues by Tau, including the gut, fat body, and reproductive system. This novel AD atlas provides valuable insights into potential biomarkers and the intricate interplay between the nervous system and peripheral tissues in response to AD-associated proteins.
CatPred: A comprehensive framework for deep learning in vitro enzyme kinetic parameterskcat,KmandKi
Authors: Boorla Veda Sheersh , Maranas Costas D.
Published: March 2024

Quantification of enzymatic activities still heavily relies on experimental assays, which can be expensive and time-consuming. Therefore, methods that enable accurate predictions of enzyme activity can serve as effective digital twins. A few recent studies have shown the possibility of training machine learning (ML) models for predicting the enzyme turnover numbers (kcat) and Michaelis constants (Km) using only features derived from enzyme sequences and substrate chemical topologies by training onin vitromeasurements. However, several challenges remain such as lack of standardized training datasets, evaluation of predictive performance on out-of-distribution examples, and model uncertainty quantification. Here, we introduce CatPred, a comprehensive framework for ML prediction ofin vitroenzyme kinetics. We explored different learning architectures and feature representations for enzymes including those utilizing pretrained protein language model features and pretrained three-dimensional structural features. We systematically evaluate the performance of trained models for predictingkcat,Km, and inhibition constants (Ki) of enzymatic reactions on held-out test sets with a special emphasis on out-of-distribution test samples (corresponding to enzyme sequences dissimilar from those encountered during training). CatPred assumes a probabilistic regression approach offering query-specific standard deviation and mean value predictions. Results on unseen data confirm that accuracy in enzyme parameter predictions made by CatPred positively correlate with lower predicted variances. Incorporating pre-trained language model features is found to be enabling for achieving robust performance on out-of-distribution samples. Test evaluations on both held-out and out-of-distribution test datasets confirm that CatPred performs at least competitively with existing methods while simultaneously offering robust uncertainty quantification. CatPred offers wider scope and larger data coverage (∼23k, 41k, 12k data-points respectively forkcat, Kmand Ki). A web-resource to use the trained models is made available at:https://tiny.cc/catpred
Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron variant JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study
Authors: de Prost Nicolas , Audureau Etienne , Guillon Antoine , Handala Lynda , Préau Sébastien , Guigon Aurélie , Uhel Fabrice , Hingrat Quentin Le , Delamaire Flora , Grolhier Claire , Tamion Fabienne , Moisan Alice , Darreau Cédric , Thomin Jean , Contou Damien , Henry Amandine , Daix Thomas , Hantz Sébastien , Saccheri Clément , Giordanengo Valérie , Pham Tài , Chaghouri Amal , Bay Pierre , Pawlotsky Jean-Michel , Fourati Slim
Published: March 2024

A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. During the study period (November 2022-January 2024), 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p=0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p=0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Day-28 mortality of JN.1-infected patients was 14.6%.
Bicuspid Aortic Valve Disease With Early Onset Complications: Characteristics And Aortic Outcomes
Authors: Selbst Maximilian A. , Laughlin Megan K. , Ward Colin R. , Michelena Hector , Sabate-Rotes Anna , Bianco Lisa , De Backer Julie , Mosquera Laura Muiño , Yetman Anji T. , Bissell Malenka M , Andreassi Maria Grazia , Foffa Ilenia , Hui Dawn S. , Caffarelli Anthony , Kim Yuli Y. , Guo Dongchuan , Citro Rodolfo , De Marco Margot , Tretter Justin T. , Morris Shaine A. , McBride Kim L. , Body Simon C. ,   EBAV Investigators, Prakash Siddharth K.
Published: March 2024

Bicuspid aortic valve (BAV) is the most common congenital heart malformation in adults but can also cause childhood-onset complications. In multicenter study, we found that adults who experience significant complications of BAV disease before age 30 are distinguished from the majority of BAV cases that manifest after age 50 by a relatively severe clinical course, with higher rates of surgical interventions, more frequent second interventions, and a greater burden of congenital heart malformations. These observations highlight the need for prompt recognition, regular lifelong surveillance, and targeted interventions to address the significant health burdens of patients with early onset BAV complications.
Common cuckoo female host selection is not determined by host quality but can affect cuckoo nestling growth when parasitising Common redstarts
Authors: Abaurrea Teresa , Moreras Angela , Tolvanen Jere , Thomson Robert L. , Thorogood Rose
Published: March 2024

Common cuckoo (Cuculus canorus) females lay their eggs in the nests of other avian hosts, relying on parental care provided by parasitised hosts. Therefore, it would benefit cuckoo females to target high-quality individual hosts, able to provide optimal parental care. Attempts at testing cuckoo female host selection have so far shown mixed results. However, this might be because studies have rarely considered the host nests that are available in space and time during each cuckoo egg-laying event, as well as the implications of host choice on the cuckoo nestling growth. Here we combined long-term monitoring data with an experiment to test whether cuckoo females parasitising Common redstarts (Phoenicurus phoenicurus) target individual hosts to optimise their nestlingś growth. Making use of data collected between 2013 and 2022 from 350+ nest boxes in Oulu (Finland), we first explored whether there is a range of available host nests for the cuckoo female to choose from. Second, we tested if hosts are targeted according to individual quality (using clutch size as a proxy). And third, we investigated the outcomes of cuckoo female host-selection on nestling growth (mass, tarsus length, and wing length) between 2014 and 2019. We conducted a cross-fostering experiment where we either left cuckoo eggs to hatch and be raised in the nest their mother originally chose for them or moved cuckoo eggs to non-parasitised nests. Additionally, we conducted an exploratory analysis to test the quality of the parents caring for the cross-fostered cuckoo nestlings. After accounting for how many host nests were available to the cuckoo female to choose from, we found that nests with bigger clutches were not more likely to be parasitised, and cross-fostering did not affect mass and tarsus length growth. However, both in the wing length growth and in our exploratory analysis of host parental care on cuckoo nestling growth we found that cuckoo nestlings that grew in the nest selected by their mothers, reached higher asymptotic growth at a slower rate. This suggests that while cuckoos may not choose redstart hosts based on their individual quality when parasitising common redstarts, cuckoo female host selection might improve cuckoo nestling growth and thus, have an adaptive significance.
A systematic exploration of unexploited genes for oxidative stress in Parkinson’s disease
Authors: Suzuki Takayuki , Bono Hidemasa
Published: March 2024

Human disease-associated gene data are accessible through databases, including the Open Targets Platform, DisGeNET, miRTex, RNADisease, and PubChem. However, missing data entries in such databases are anticipated because of factors, such as errors/biases by curators and text mining failures. Additionally, the extensive research on human diseases has resulted in challenges to register comprehensive data. The lack of essential data in databases hinders knowledge sharing and should be addressed. Therefore, we propose an analysis pipeline to explore missing entries of unexploited genes in the human disease-associated gene databases. To demonstrate this, we used the pipeline for genes in Parkinson’s disease with oxidative stress, which revealed two unexploited genes: nuclear protein 1 (NUPR1) and ubiquitin-like with PHD and ring finger domains 2 (UHRF2). The proposed methodology and findings facilitate the identification of disease-associated genes that are not completely represented in existing databases, thereby facilitating easier access to the potential human disease-related functional genes.
Negative impact of mild arid conditions in natural rodent populations revealed using markers of physiological condition in natura
Authors: Keilani Hamilcar , Avenant Nico , Caminade Pierre , Pillay Neville , Ganem Guila
Published: March 2024

Understanding how organisms respond to seasonal variations in their environment can be a window to their potential adaptability, a classical problem in evolutionary ecology. In the context of climate change, inducing increased aridity and disruption of seasonality, it is crucial to study the extent and limits of species responsiveness.

Here, the physiological response to food and water shortage during seasonally dry conditions were investigated. We studied populations of two rodent species of the genusRhabdomys, one arid and one mesic, in a semi-arid zone where their range overlap in South Africa. We measured blood concentrations of markers of kidney and liver function, as well as body condition, at the onset and the end of the dry season.

We found similar shifts in blood metabolite levels, in the semi-arid populations of the two species, indicating malnutrition consistent with the observed degradation of habitat quality between the start and the end of the dry season. Furthermore, regardless of the period, differences between the two species in blood metabolite concentrations (e.g. amylase, sodium, alkaline phosphatase) were observed, suggesting contrasting diets and water conservation abilities.

Overall, we show that, as seasonal dry conditions worsen, organisms are increasingly affected by reduced food availability, and local adaptation to arid conditions may provide the arid species with an advantage to cope with semi-arid conditions. Our study suggests that even mild arid conditions could have a negative impact and questions resilience of animals to harsher arid conditions.
Beyond blooms: A novel time series analysis framework predicts seasonal keystone species and sheds light on Arctic pelagic ecosystem stability
Authors: Oldenburg Ellen , Kronberg Raphael M. , Metfies Katja , Wietz Matthias , von Appen Wilken-Jon , Bienhold Christina , Popa Ovidiu , Ebenhöh Oliver
Published: March 2024

A thorough understanding of ecosystem functioning in the Arctic Ocean, a region under severe threat by climate change, requires detailed studies on linkages between biodiversity and ecosystem stability. The identification of keystone species with special relevance for ecosystem stability is of great importance, yet difficult to achieve with established community assessments. In the case of microbes, metabarcoding and metagenomics offer fundamental insights into community structure and function, yet remain limited regarding the ecological relevance of individual taxa. To overcome this limitation, we have developed an analytical approach based on three different methods: Co-Occurrence Networks, Convergent Cross Mapping, and Energy Landscape Analysis. These methods enable the identification of seasonal communities in microbial ecosystems, elucidate their interactions, and predict potential stable community configurations under varying environmental conditions. Combining the outcomes of these three methods allowed us to define 38 keystone species in the Arctic Fram Strait that represent different trophic modes within the food web, and might signify indicator for ecosystem functionality under the impact of environmental change. Our research reveals a clear seasonal pattern in phytoplankton composition, with distinct assemblages characterizing the phases of carbon fixation (polar day) and consumption (polar night). Species interactions exhibited strong seasonality, with significant influence of summer communities on winter communities but not vice versa. Spring harbored two distinct groups: consumers (heterotrophs), strongly linked to polar night, and photoautotrophs (mainly Bacillariophyta). These groups are not causally related, suggesting a “winter reset” with selective effects that facilitates a new blooming period, allowing survivors of the dark phase to emerge. Energy Landscape Analysis showed that winter communities are more stable than summer communities. In summary, the ecological landscape of the Fram Strait can be categorized into two distinct phases: a production phase governed by specialized organisms that are highly responsive to environmental variability, and a heterotrophic phase dominated by generalist species with enhanced resilience.
Phylogenetically distant enzymes localized in cytosol and plastids drive citral biosynthesis in lemongrass
Authors: Gupta Priyanka , Sharma Anuj , Kiran N.R. , Pranav Raj T.K. , Krishna Ram , Nagegowda Dinesh A.
Published: March 2024

Except for the genetic basis of citral-forming alcohol dehydrogenases (ADHs) inLitsea cubebatree, and biochemical studies on citral-forming enzymes from select plants, knowledge regardingin-plantabiosynthesis of citral and its metabolic origin remains limited. Here, we have elucidated the functions of an ADH (CfADH1) and an aldoketo-reductase (CfAKR2b) in citral biosynthesis in lemongrass (Cymbopogon flexuosus), one of the most cultivated aromatic crops for its citral-rich essential oil. Expression of bothCfADH1andCfAKR2bshowed correlation with citral accumulation in different developmental stages. Recombinant CfADH1 and CfAKR2b, despite their sequence unrelatedness, exhibited similar kinetic properties and formed citral from geraniol with NADP cofactor. Virus-induced gene silencing in lemongrass, and transient expression in lemon balm (Melissa officinalis), demonstrated thein-plantainvolvement ofCfADH1andCfAKR2bin citral biosynthesis. While CfADH1 exhibited a dual cytosolic/plastidial localization, CfAKR2b was localized to cytosol. Moreover, feeding lemongrass seedlings with mevalonate- and methylerythritol-phosphate-pathway specific inhibitors combined with volatile profiling supported the role of both pathways in citral formation. Our results demonstrate phylogenetically distant enzymes localized in cytosol and plastids drive citral biosynthesis in lemongrass, indicating an evolutionary scenario aimed at maximizing the utilization of precursor pools from both cytosolic and plastidial pathways for high citral production.
Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated F-actin remodeling
Authors: Lin Kun-Yang , Gujar Mahekta R. , Lin Jiaen , Ding Wei Yung , Huang Jiawen , Gao Yang , Tan Ye Sing , Teng Xiang , Christine Low Siok Lan , Kanchanawong Pakorn , Toyama Yusuke , Wang Hongyan
Published: March 2024

The transitioning of neural stem cells (NSCs) between quiescent and proliferative states is fundamental for brain development and homeostasis. Defects in NSC reactivation are associated with neurodevelopmental disorders.Drosophilaquiescent NSCs extend an actin-rich primary protrusion toward the neuropil. However, the function of the actin cytoskeleton during NSC reactivation is unknown. Here, we reveal the fine F-actin structures in the protrusions of quiescent NSCs by expansion and super-resolution microscopy. We show that F-actin polymerization promotes the nuclear translocation of Mrtf, a microcephaly-associated transcription factor, for NSC reactivation and brain development. F-actin polymerization is regulated by a signaling cascade composed of G-protein-coupled receptor (GPCR) Smog, G-protein αq subunit, Rho1 GTPase, and Diaphanous (Dia)/Formin during NSC reactivation. Further, astrocytes secrete a Smog ligand Fog to regulate Gαq-Rho1-Dia-mediated NSC reactivation. Together, we establish that the Smog-Gαq-Rho1 signaling axis derived from astrocytes, a NSC niche, regulates Dia-mediated F-actin dynamics in NSC reactivation.
Freshwater fish egg dispersal by attaching to waterbirds
Authors: Yao Akifumi , Mashiko Miyuki , Toquenaga Yukihiko
Published: March 2024

Dispersal over geographic barriers plays an essential role in colonization, gene flow, metapopulation dynamics, and invasion (Bowler and Benton 2005). Since dry lands strictly separate freshwater habitats, as expressed by the phrase “islands of water in a sea of dry land” (Faulks, Gilligan, and Beheregaray 2010), dispersal among freshwater waterbodies by themselves is challenging of aquatic organisms. Rumors have existed worldwide that freshwater fish eggs are dispersed by attaching to (ectozoochory) or excretion from (endzoochory) waterbirds (Hirsch et al. 2018). It is well documented that waterbirds disperse aquatic plants, zooplankton, and various aquatic invertebrates, which are co-distributed with fishes (Green et al. 2023). However, there is only two reported cases of empirical evidence of endzoochory in freshwater fishes and no scientific evidence of ectozoochory (Hirsch et al. 2018; Silva et al. 2019; Lovas-Kiss et al. 2020; Green et al. 2023). Here, we show that the southern medaka (Oryzias latipes, hereafter medaka) egg can travel passively by attaching to waterbirds.
Rejuvenation of aged oocyte through exposure to young follicular microenvironment
Authors: Wang HaiYang , Huang Zhongwei , Lee Yaelim , Song XinJie , Shen Xingyu , Shu Chang , Wu Lik Hang , Pakkiri Leroy Sivappiragasam , Lim Poh Leong , Zhang Xi , Drum Chester Lee , Zhu Jin , Li Rong
Published: March 2024

Reproductive aging is a major cause of fertility decline, attributed to decreased oocyte quantity and competence. Follicular somatic cells play crucial roles in the growth and development of the oocyte by providing nutrients and regulatory factors. Here we investigated how oocyte quality is affected by its somatic cell environment by creating chimeric follicles, whereby an oocyte from one follicle was transplanted into and cultured within another follicle whose native oocyte was removed. Somatic cells within the chimeric follicle re-establish connections with the oocyte and support oocyte growth and maturation in a three-dimensional (3D) culture system. We show that young oocytes transplanted into aged follicles exhibited reduced meiotic maturation and developmental potential, whereas the young follicular environment significantly improved the rates of maturation, blastocyst formation and live birth of aged oocytes. Aged oocytes cultured within young follicles exhibited enhanced interaction with somatic cells, more youth-like transcriptome, remodelled metabolome, improved mitochondrial function, and enhanced fidelity of meiotic chromosome segregation. These findings provide the basis for a future follicular somatic cell-based therapy to treat age-associated female infertility.