bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-distance gene flow and recombination shape the evolutionary history of a maize pathogen
Authors: Rogério Flávia , Oosterhout Cock Van , De Mita Stéphane , Cuevas-Fernández Francisco Borja , García-Rodríguez Pablo , Becerra Sioly , Gutiérrez-Sánchez Silvia , Jacquat Andrés G. , Bettiol Wagner , Hosaka Guilherme Kenichi , Ulla Sofia B. , Hiltbrunner Jürg , Santiago Rogelio , Revilla Pedro , Dambolena José S. , Vicente-Villardón José L. , Buhiniček Ivica , Sukno Serenella A. , Thon Michael R. 
Published: July 2024

AbstractThe evolutionary history of crop pathogens is shaped by a complex interaction of natural and anthropogenic factors. The ascomycete fungusColletotrichum graminicolacauses maize anthracnose. The disease can result in significant yield losses and is also an important model for genetic studies. We conducted a comprehensive investigation into the evolutionary genomics ofC. graminicolausing a collection of 212 isolates from 17 countries. Genomic analyses supported the existence of three geographically isolated genetic lineages, with a significant pattern of isolation by distance. We identified two distinct gene flow patterns, driven by short and long-distance dispersion, likely resulting from the natural spread of the pathogen and the exchange of contaminated seeds. We present evidence of genetic introgression between lineages, suggesting a long history of recombination. We identified significant recombination events coalescing at distinct points in time, with the North American lineage displaying evidence of most ancient recombination. Demographic modeling indicated that North America is an intermediate between Brazil, Europe and an ancestral, unsampled source population, hypothesized to be Mesoamerican. Our analyses revealed that the global genomic structure ofC. graminicolais shaped by geographic differentiation driven by long-distance migration and a long history of recombination and introgression. We show historical relationships among these lineages, identifying a potential route for fungal spread, with the North American population emerging ancestrally, followed sequentially by the Brazilian and European populations. Our research indicates that the European lineage is more virulent, which has implications for the potential emergence of new outbreaks of maize anthracnose in Europe.
Drivers of temporal bias in biodiversity recording by citizen scientists
Authors: Rosário Inês.T. , Tiago Patrícia. , Chozas Sergio , Capinha César 
Published: July 2024

AbstractCitizen science data is increasingly important for ecological research, biodiversity conservation and monitoring. However, these data often suffer from biases due to uneven recording efforts by citizen scientists. Biases caused by intra-annual differences in recording activity can be particularly severe, hindering the use of citizen science data in research areas such as population dynamics and phenology. Therefore, understanding the factors driving recording activity is essential.In this study, we provide a detailed assessment of how weather and calendar-related factors influence biodiversity recording activity by citizen scientists at a daily resolution. To perform this, we analyse the recording patterns for six tree species in the Iberian Peninsula, which maintain a fairly consistent appearance throughout the year. Observation data were collected from iNaturalist, a leading platform for citizen-science data. We used boosted regression trees (BRT) to compare observed recording activity patterns with those expected by chance. Our analysis included a comprehensive set of explanatory variables, such as day of the week, month, holidays, temperature, accumulated precipitation, wind intensity, and snow depth.The BRT models effectively identified the drivers of recording activity, with the correlation between predicted and observed temporal patterns (left out of model training) ranging from 0.47 to 0.96, depending on the species. The day of the week, daily temperature, and month of the year consistently emerged as the main drivers. Recording activity was higher on weekends, to some extent on Fridays, and during the spring months. Extreme low and high temperatures generally correlated with lower recording activity, although there were exceptions. Wind speed and precipitation had a moderate influence, with higher wind intensity and accumulated precipitation leading to decreased activity. Holidays and accumulated snow had very minor relevance across species.Our findings show that citizen scientists record more frequently on weekends, during mild weather, and in spring. By addressing these biases, we can maximize the utility of citizen-collected data for research and applied purposes, ensuring robust and reliable conclusions that enhance ecological understanding and conservation efforts.
Investigating the temporal effects of ovarian failure on single muscle fibre contractility using a chemically-induced ovarian failure model in mice
Authors: Mashouri Parastoo , Saboune Jinan , Pyle W. Glen , Power Geoffrey A. 
Published: July 2024

AbstractWe investigated the effects of chemically-induced ovarian failure on single muscle fibre contractility of the soleus and extensor digitorum longus (EDL) muscles throughout ovarian failure, thereby mimicking the menopausal transition into late-stage menopause: [(D60;peri-menopause), (D120;onset of menopause), (D134;early-onset menopause), (D176;late-stage menopause)]. We used 4-vinylcyclohexene diepoxide (VCD) to induce ovarian failure in sexually-mature female mice. At D120 and D176, mice with VCD-induced ovarian failure produced higher force as compared with controls (p<0.05). On D134, however, VCD had lower force production compared with controls (p<0.05). The cross-sectional area of the soleus fibres from the VCD group was larger at D120 compared with controls (p<0.05), but not at any other time point (p>0.05). As well, at D120-D176, the proportion of Type II fibres relative to Type I increased for the soleus, but not the EDL. No differences in rate of force redevelopment (Ktr) was observed for the soleus (p>0.05), while calcium sensitivity increased by late-stage menopause (p<0.05). There were no differences in force, cross-sectional area, stiffness, Ktr, or calcium sensitivity between groups for the EDL (p>0.05). Muscle contractility across the peri-menopausal transition into late-stage menopause is both muscle and phase-dependent, emphasizing the complexity of changing hormones throughout the lifespan on muscle contractile function.
RAF2Net: Automated grading of Renal cell Carcinoma utilizing Attention-enhanced deep learning models through Feature Fusion
Authors: Kundu Shreyan , Roy Nirban , Talukdar Rahul , Das Semanti , Mukhopadhyay Souradeep , Basu Mallik Biswadip 
Published: July 2024

AbstractIt is anticipated that the number of instances of kidney cancer will continue to rise globally, which motivates changes to the current diagnostic framework in order to address emerging issues. Renal cell carcinoma (RCC) accounts for 80–85% of all renal tumors and is the most common kind of kidney cancer. Based on kidney histopathology images, this study presented a completely automated, robust, and computationally efficient Renal Cell Carcinoma Grading Network (RAF2Net). Our suggested model incorporates 3 different Mobilenet backbones with intelligent feature fusion. Moreover, the attention blocks help us give more importance to the important pixels, which are majorly responsible for classification. For comparison purposes, Similar tests were conducted using transfer learning methods with pre-trained ImageNet weights and deep learning models created from scratch. To show the efficacy of the suggested method, we have computed evaluation parameters like Accuracy, Precision, F score, Recall, Confusion Matrix, and TSNE. Based on the provided KMC dataset, the experimental result demonstrates that the proposed RAF2Net outperforms the nine most recent classification methods regarding prediction Accuracy, Recall, Precision, and F score with a value greater than 92%.
Transient Non-local Interactions Dominate the Dynamics of Measles Virus NTAIL
Authors: Otteson Lillian , Nagy Gabor , Kunkel John , Kodis Gerdenis , Zheng Wenwei , Bignon Christophe , Longhi Sonia , Grubmüller Helmut , Vaiana Andrea C. , Vaiana Sara M. 
Published: July 2024

AbstractThe RNA genome of measles virus is encapsidated by the nucleoprotein within a helical nucleocapsid that serves as template for both transcription and replication. The intrinsically disordered domain of the nucleoprotein (NTAIL), partly protruding outward from the nucleocapsid, is essential for binding the polymerase complex responsible for viral transcription and replication. As for many IDPs, binding of NTAILoccurs through a short molecular recognition element (MoRE) that folds upon binding, with the majority of NTAILremaining disordered. Though NTAILregions far from the MoRE influence the binding affinity, interactions between them and the MoRE have not been investigated in depth. Using an integrated approach, relying on photo-induced electron transfer (PET) experiments between tryptophan and cysteine pairs placed at different positions in the protein under varying salt and pH conditions, combined with simulations and analytical models, we identified transient interactions between two disordered regions distant in sequence, which dominate NTAILdynamics, and regulate the conformational preferences of both the MoRE and the entire NTAILdomain. Co-evolutionary analysis corroborates our findings, and suggests an important functional role for the same intramolecular interactions. We propose mechanisms by which these non-local interactions may regulate binding to the phosphoprotein, polymerase recruitment, and ultimately viral transcription and replication. Our findings may be extended to other IDPs, where non-local intra-protein interactions affect the conformational preferences of intermolecular binding sites.
A potent and selective reaction hijacking inhibitor ofPlasmodium falciparumtyrosine tRNA synthetase exhibits single dose oral efficacyin vivo
Authors: Xie Stanley C. , Tai Chia-Wei , Morton Craig J. , Ma Liting , Huang Shih-Chung , Wittlin Sergio , Du Yawei , Hu Yongbo , Dogovski Con , Salimimarand Mina , Griffin Robert , England Dylan , de la Cruz Elisa , Deni Ioanna , Yeo Tomas , Burkhard Anna Y. , Striepen Josefine , Schindler Kyra A. , Crespo Benigno , Gamo Francisco J. , Khandokar Yogesh , Hutton Craig A. , Rabie Tayla , Birkholtz Lyn-Marié , Famodimu Mufuliat T. , Delves Michael J. , Bolsher Judith , Koolen Karin M. J. , van der Laak Rianne , Aguiar Anna C. C. , Pereira Dhelio B. , Guido Rafael V. C. , Creek Darren J. , Fidock David A. , Dick Lawrence R. , Brand Stephen L. , Gould Alexandra E. , Langston Steven , Griffin Michael D.W. , Tilley Leann 
Published: July 2024

AbstractThePlasmodium falciparumcytoplasmic tyrosine tRNA synthetase (PfTyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidine ribose sulfamate, ML901, as a potent pro-inhibitor ofPfTyrRS. Here we examined the stage specificity of action of ML901, showing very good activity against the schizont stage, but lower trophozoite stage activity. We explored a series of ML901 analogues and identified ML471, which exhibits improved potency against trophozoites and enhanced selectivity against a human cell line. Additionally, it has no inhibitory activity against human ubiquitin-activating enzyme (UAE)in vitro. ML471 exhibits low nanomolar activity against asexual blood stageP. falciparumand potent activity against liver stage parasites, gametocytes and transmissible gametes. It is fast-acting and exhibits a longin vivohalf-life. ML471 is well-tolerated and shows single dose oral efficacy in the SCID mouse model ofP. falciparummalaria. We confirm that ML471 is a pro-inhibitor that is converted into a tight binding Tyr-ML471 conjugate by thePfTyrRS enzyme. A crystal structure of thePfTyrRS/ Tyr-ML471 complex offers insights into improved potency, while molecular docking into UAE provides a rationale for improved selectivity.
Enhanced anti-tumor effects through continuous administration of engineered CAR-macrophages derived from pluripotent stem cell-derived myeloid cell lines
Authors: Atsumi Yuya , Niwa Akira , Kumaki Tatsuro , Yagyu Shigeki , Nakazawa Yozo , Saito Megumu K. 
Published: July 2024

AbstractEven after chimeric antigen receptor (CAR)-based immunotherapy has dramatically changed therapeutic approaches for malignancies, balancing therapeutic efficacy with labor and financial cost remains a major problem for immunotherapy. Current study developed a cost-effective and enhanced approach to chimeric antigen receptor (CAR)-macrophage therapy for cancer and demonstrated its therapeutic effects by repeated administration of anti-HER2 CAR macrophages generated from human pluripotent stem cell (PSC)-derived immortalized myeloid cell lines (ML). These ML-derived CAR macrophages (CAR-ML-MPs) exhibit potent antigen-specific killing activity against HER2-expressing tumor cells by phagocytosisin vitroand effectively inhibit tumor progressionin vivo, which is enhanced by repeated administration. CAR-ML-MPs provide a promising off-the-shelf cellular resource for tumor adoptive cell immunotherapy, solving the cost and time problems associated with conventional CAR-based immunotherapy.
Boosting the Predictive Power of Protein Representations with a Corpus of Text Annotations
Authors: Duan Haonan , Skreta Marta , Cotta Leonardo , Rajaonson Ella Miray , Dhawan Nikita , Aspuru-Guzik Alán , Maddison Chris J. 
Published: July 2024

AbstractProtein language models are trained to predict amino acid sequences from vast protein databases, while learning to represent proteins as feature vectors. These vector representations have enabled impressive applications, from predicting mutation effects to protein folding. One of the reasons offered for the success of these models is that conserved sequence motifs tend to be important for protein fitness. Yet, the relationship between sequence conservation and fitness can be confounded by the evolutionary and environmental context. Should we therefore look to other data sources that may contain more direct functional information? In this work, we conduct a comprehensive study examining the effects of training protein models to predict nineteen types of text annotations from UniProt. Our results show that finetuning protein models on a subset of these annotations enhances the models’ predictive capabilities on a variety of function prediction tasks. Notably, our model outperforms the search algorithm BLAST, which none of the pre-trained protein models accomplished in our evaluation. Our results suggest that a much wider array of data modalities, such as text annotations, may be tapped to improve protein language models. We host our model checkpoints onhttps://huggingface.co/h4duan.
Highly ordered clustering of TNFα and BAFF ligand-receptor-adaptor complexes bound to lipid membranes
Authors: Lim Chan Seok , Lee Jisun , Kim Ji Won , Lee Jie-Oh 
Published: July 2024

SUMMARYWe report the cryo-EM structures of clusters of TNF receptor family proteins, TNFR1 and BAFFR. The receptor-ligand complexes were anchored to a flat lipid layer to mimic the membrane-bound state. We observed that the TNFα-TNFR1 complex forms highly ordered binary, bent, trigonal, and linear quadruple clusters of trimers on the lipid membrane. A non-competitive antagonist of TNFR1 disrupted these clusters without interfering with ligand binding. Moreover, we found that the BAFF-BAFFR complex forms pentagonal, double-pentagonal, or half-spherical clusters of trimers. Mutations in BAFF that inhibit BAFFR receptor activation prevented ordered clustering without disrupting receptor binding. TRAF3 induced a structural shift in the BAFF-BAFFR cluster, resulting in a flat hexagonal cluster. Our data demonstrated that precisely structured clustering is essential for the activation of these receptors. The lipid monolayer method will aid in studying the clusters of other transmembrane proteins and facilitate the discovery of therapeutic agents that regulate their clustering.
Metabolic profiling using benchtop NMR identifies the metabolomic signature of persistent CAR-T cells
Authors: Song Suk-Heung , Ryan Herb , Hoefflin Jens , Kyung Taeyoon , Mace Joshua , Raman Jai , Eshghi Shawdee 
Published: July 2024

AbstractAnalytical technologies for engineered biological systems hold great promise in addressing various challenges in modern pharmaceuticals and biomedical therapies. These endeavors often follow a design-build-test-learn approach, utilizing biological data from genetic circuits, signal pathways, metabolites, and proteins to optimize biological systems. Deciphering large and intricate datasets can prove to be a formidable task. Principal component analysis (PCA) tool is an invaluable method for reducing dataset complexity and enhancing interpretability while minimizing information loss, simultaneously. PCA tool achieves this by creating new, uncorrelated variables that capture the maximum variance in the data. Herein chimeric antigen receptors (CARs) T cells metabolomic study presents a slightly inverse problem, where PCA is applied to model sparse extracellular metabolites data from CAR-T cells, resulting in a two-component model. Using an benchtop NMR spectrometer only six metabolites could be annotated, nevertheless, the PCA model could identify differences in the metabolites of CAR-T cells based on the design of CARs, specifically the combinations of the intracellular domain (ICDs). It’s noteworthy that the behavior and fate of CAR-T cells are distinctly influenced by the type of ICDs used upon antigen recognition.
Size evolution of gigantic genomes suggests stochastic outcomes of transposable element/host silencing interactions
Authors: Wang Jie , Zhang Guangpu , Sun Cheng , Chang Liming , Wang Yingyong , Yang Xin , Chen Guiying , Itgen Michael W. , Haley Ava , Tang Jiaxing , Mueller Rachel Lockridge 
Published: July 2024

AbstractSize evolution among gigantic genomes involves gain and loss of many gigabases of transposable elements (TEs), sequences that parasitize host genomes. Animals suppress TEs using piRNA and KRAB-ZFP pathways. TEs and hosts coevolve in an arms race, where suppression strength reflects TE fitness costs. In enormous genomes, additional TE costs become miniscule. How, then, do TEs and host suppression invoke further addition of massive DNA amounts? We analyzed TE proliferation histories, deletion rates, and community diversities in six salamander genomes (21.3 - 49.9 Gb), alongside gonadal expression of TEs and suppression pathways. TE activity is higher in testes than ovaries, attributable to lower KRAB-ZFP suppression. Unexpectedly, genome size/expansion is uncorrelated with TE deletion rate, proliferation history, expression, and host suppression. Also, TE community diversity increases with genome size, contrasting theoretical predictions. TE/host antagonism in gigantic genomes likely produces stochastic TE accumulation, determined by noisy intermolecular interactions in huge genomes/cells.
Relevance of the synergy of surveillance and populational networks in understanding the Usutu virus outbreak within common blackbirds (Turdus merula) in Metropolitan France, 2018
Authors: Bouchez-Zacria Malika , Calenge Clément , Villers Alexandre , Lecollinet Sylvie , Gonzalez Gaelle , Quintard Benoit , Leclerc Antoine , Baurier Florence , Paty Marie-Claire , Faure Éva , Eraud Cyril , Decors Anouk 
Published: July 2024

AbstractUsutu virus (USUV) was first isolated in Africa in 1959 and has since spread to and through Europe with a typical enzootic mosquito-bird cycle. In France, it was first detected in birds in 2015, but during summer 2018 the spread of USUV was particularly significant throughout the country, killing mainly common blackbirds (Turdus merula) and to a lesser extent great grey owls (Strix nebulosa), among other captive and non-captive wild bird species. Previous studies of USUV in France have focused on reconstructing pathways of introduction, but not on structural aspects of virus spread within the country. Data (RT-PCR of geolocated dead birds) on this 2018 outbreak were collected through both an event-based wildlife network named SAGIR and the health surveillance of the French-speaking Association of Zoo Veterinarians (AFVPZ). In addition, common blackbird populations could be monitored through another network (REZOP). Statistical analysis (spatial, temporal, spatiotemporal and environmental determinants) of the SAGIR and AFVPZ network data helped to highlight the early appearance of separate large clusters of USUV cases in mid-July 2018, the subsequent diffusion into smaller and secondary clusters at the end of August 2018, and a meanwhile enlargement of the first clusters with an increase in the number of cases. High human density (top 10.5% densest areas in France) and wetland concentration (top 19.3% most likely wetland areas) were significant factors in USUV case locations. Using generalised additive mixed models on REZOP data, we also highlighted the decline in common blackbird population trends in areas with medium and even more with high USUV pressure (areas defined based on SAGIR-AFVPZ data) following the 2018 outbreak (respectively −7.4% [−11.4; −3.9]95%and −15.7% [−16.2; −9.1]95%). A large area (radius ∼150 km) in the centre and centre-west of France, and smaller areas in the south-east, north and north-east of France (each with a radius ∼ 50 km) were particularly affected. We conclude on the importance to work with synergistic networks to assess infection spread in wild bird species, as well as the negative impact of an emerging arbovirus. The responsiveness of such a network system could be improved by automating alerts.
Assessing the effectiveness of multi-session online emotion recognition training in autistic adults
Authors: Reed Zoe E , Bastiani Oliver , Eastwood Andy , Penton-Voak Ian S , Jarrold Christopher , Munafò Marcus R , Attwood Angela S 
Published: July 2024

AbstractPurposeDifficulties with emotion recognition can occur in neurodevelopmental conditions, including in autistic individuals. Providing interventions to support this would therefore be beneficial, particularly in terms of downstream effects on wellbeing, social relationships and education.MethodsIn this online experimental study, we examined the effect of a recently developed facial emotion recognition training task versus a sham/control task in an adult population identifying as autistic over four sessions in a 2-week period, with a fifth follow-up session (N=184).ResultsOur main analyses showed that facial emotion recognition accuracy was greater in Session 4 in the active group, with an estimated improvement of 14% (equivalent to approximately 7 additional correct responses), compared to 2% (equivalent to approximately 1 additional correct responses) in the sham group. Additional analyses suggested training effects were generalisable to facial stimuli that participants had not been trained on and were still present, although attenuated, two weeks later. We also observed some self-reported improvements in social interactions post-training.ConclusionOverall, this study demonstrated improved emotion recognition in an adult autistic sample with this training task. Future work is needed to investigate the effect of this emotion recognition training on emotion recognition accuracy in autistic children, where support could be most beneficial.