bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of landscape partitioning indicate low levels of resource competition among neighbouring Guinea baboon (Papio papio) parties
Authors: Ohrndorf Lisa , Mundry Roger , Beckmann Jörg , Fischer Julia , Zinner Dietmar 
Published: September 2024

AbstractBackgroundAccess to critical resources, including food, water, or shelter, significantly determines individual fitness. As these resources are limited in most habitats, animals may employ strategies of landscape partitioning to mitigate the impact of direct resource competition. Territoriality may be regarded as an aggressive form of landscape partitioning but in non-territorial species, other forms exist. Animals living in groups with greater flexibility in their association patterns, such as multilevel societies with fission-fusion dynamics, may adjust their grouping and space use patterns to short-term variations in ecological conditions such as food availability, predation pressure, or the presence of conspecific groups. This flexibility may allow them to balance the costs of competition while reaping the benefits of better predator detection and defence.MethodsWe explored patterns of landscape partitioning among neighbouring Guinea baboon (Papio papio) parties in the Niokolo-Koba National Park, Senegal. Guinea baboons live in a multilevel society in which parties predictably form higher-level associations (“gangs”). We used four years of locational data from individuals equipped with GPS collars to estimate annual home ranges, home range overlap, and minimum distances between parties. We examined whether food availability and predator presence levels affected the cohesion between parties in 2022.ResultsWe found substantial home range and core area overlap among parties (33 to 100%). We found no effect of food availability or predator presence on the distance to the closest neighbouring party; the minimum distance between parties was less than 100 m on average.ConclusionsOur results suggest a low level of feeding competition between our study parties. Whether this is a general feature of Guinea baboons or particular to the situation in the Niokolo-Koba National Park remains to be investigated.
Modulation of Stemness and Differentiation Regulators by Valproic Acid in Medulloblastoma Neurospheres
Authors: Freire Natália Hogetop , Herlinger Alice Laschuk , Vanini Julia , Dalmolin Matheus , Fernandes Marcelo A. C. , Nör Carolina , Ramaswamy Vijay , Brunetto de Farias Caroline , Brunetto André Tesainer , Brunetto Algemir Lunardi , Gregianin Lauro José , da Cunha Jaeger Mariane , Taylor Michael D. , Roesler Rafael 
Published: September 2024

AbstractChanges in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest. These effects were accompanied by enhanced H3K9 histone acetylation (H3K9ac) and decreased expression of theMYConcogene. VPA impaired the expansion of MB neurospheres enriched in stemness markers and reducedMYCwhile increasingTP53expression in these neurospheres. In addition, VPA induced morphological changes consistent with neuronal differentiation and the increased expression of differentiation marker genesTUBB3andENO2. The expression of stemness genesSOX2,NES, andPRTGwas differentially affected by VPA in MB cells with differentTP53status. VPA increased H3K9 occupancy of the promoter region ofTP53. Among the genes regulated by VPA, the stemness regulatorsMYCandNESshowed an association with patient survival in specific MB subgroups. Our results indicate that VPA may exert antitumor effects in MB by influencing histone acetylation, which may result in the modulation of stemness, neuronal differentiation, and the expression of genes associated with patient prognosis in specific molecular subgroups. Importantly, the actions of VPA in MB cells and neurospheres include a reduction in the expression ofMYCand an increase inTP53.
Clustering individuals using INMTD: a novel versatile multi-view embedding framework integrating omics and imaging data
Authors: Li Zuqi , Windels Sam F. L. , Malod-Dognin Noël , Weinberg Seth M. , Marazita Mary L. , Walsh Susan , Shriver Mark D. , Fardo David W. , Claes Peter , Pržulj Nataša , Van Steen Kristel 
Published: September 2024

AbstractMotivationCombining omics and images, can lead to a more comprehensive clustering of individuals than classic single-view approaches. Among the various approaches for multi-view clustering, nonnegative matrix tri-factorization (NMTF) and nonnegative Tucker decomposition (NTD) are advantageous in learning low-rank embeddings with promising interpretability. Besides, there is a need to handle unwanted drivers of clusterings (i.e. confounders).ResultsIn this work, we introduce a novel multi-view clustering method based on NMTF and NTD, named INMTD, that integrates omics and 3D imaging data to derive unconfounded subgroups of individuals. In the application to real-life facial-genomic data, INMTD generated biologically relevant embeddings for individuals, genetics and facial morphology. By removing confounded embedding vectors, we derived an unconfounded clustering with better internal and external quality; the genetic and facial annotations of each derived subgroup highlighted distinctive characteristics. In conclusion, INMTD can effectively integrate omics data and 3D images for unconfounded clustering with biologically meaningful interpretation.Availability and implementationhttps://github.com/ZuqiLi/INMTD
Impact of complex spatial population structure on early and long-term adaptation in rugged fitness landscapes
Authors: Servajean Richard , Alexandre Arthur , Bitbol Anne-Florence 
Published: September 2024

AbstractWe study how rugged fitness landscapes are explored by spatially structured populations with demes on the nodes of a graph, connected by migrations. In the weak mutation and rare migration regime, we find that, in most landscapes, migration asymmetries associated with some suppression of natural selection allow the population to reach higher fitness peaks first. In this sense, suppression of selection can make early adaptation more efficient. However, the time it takes to reach the first fitness peak is then increased. We also find that suppression of selection tends to enhance finite-size effects. Finite structures can adapt more efficiently than very large ones, especially in high-dimensional fitness landscapes. We extend our study to frequent migrations, suggesting that our conclusions hold in this regime. We then investigate the impact of spatial structure with rare migrations on long-term evolution by studying the steady state of the population with weak mutation, and introducing an associated steady-state effective population size. We find that suppression of selection is associated to small steady-state effective population sizes, and thus to small average steady-state fitnesses.
An optimized pipeline for high-throughput bulk RNA-Seq deconvolution illustrates the impact of obesity and weight loss on cell composition of human adipose tissue
Authors: Ahn Cheehoon , Divoux Adeline , Zhou Mingqi , Seldin Marcus M , Sparks Lauren M , Whytock Katie L 
Published: September 2024

SUMMARYCellular heterogeneity of human adipose tissue, is linked to the pathophysiology of obesity and may impact the response to energy restriction and changes in fat mass. Here, we provide an optimized pipeline to estimate cellular composition in human abdominal subcutaneous adipose tissue (ASAT) from publicly available bulk RNA-Seq using signature profiles from our previously published full-length single nuclei (sn)RNA-Seq of the same depot. Individuals with obesity had greater proportions of macrophages and lower proportions of adipocyte sub-populations and vascular cells compared with lean individuals. Two months of diet-induced weight loss (DIWL) increased the estimated proportions of macrophages; however, two years of DIWL reduced the estimated proportions of macrophages, thereby suggesting a bi-phasic nature of cellular remodeling of ASAT during weight loss. Our optimized high-throughput pipeline facilitates the assessment of composition changes of highly characterized cell types in large numbers of ASAT samples using low-cost bulk RNA-Seq. Our data reveal novel changes in cellular heterogeneity and its association with cardiometabolic health in humans with obesity and following weight loss.Lead contactKatie Whytock (Katie.Whytock@adventhealth.com)
A comparative assessment of self-limiting genetic control strategies for population suppression
Authors: Han Yue , Champer Jackson 
Published: September 2024

AbstractGenetic control strategies are promising solutions for control of pest populations and invasive species. Methods utilizing repeated releases of males such as Sterile Insect Technique (SIT), Release of Insects carrying a Dominant Lethal (RIDL), self-limiting gene drives, and gene disruptors are highly controllable methods, ensuring biosafety. Although models of these strategies have been built, detailed comparisons are lacking, particularly for some of the newer strategies. Here, we conducted a thorough comparative assessment of self-limiting genetic control strategies by individual-based simulation models. Specifically, we find that repeated releases greatly enhance suppression power of weak and self-limiting gene drives, enabling population elimination with even low efficiency and high fitness costs. Moreover, dominant female sterility further strengthens self-limiting systems that can either use gene drive or disruptors that target genes without a mechanism to bias their own inheritance. Some of these strategies are highly persistent, resulting in relatively low release ratios even when released males suffer high fitness costs. To quantitively evaluate different strategies independent from ecological impact, we proposed constant-population genetic load, which achieves over 95% accuracy in predicting simulation outcomes for most strategies, though it is not as precise in a few frequency-dependent systems. Our results suggest that many new self-limiting strategies are safe, flexible, and more cost-effective than traditional SIT and RIDL, and thus have great potential for population suppression of insects and other pests.
High-Throughput Empirical and Virtual Screening to Discover Novel Inhibitors of Polyploid Giant Cancer Cells in Breast Cancer
Authors: Ma Yushu , Shih Chien-Hung , Cheng Jinxiong , Chen Hsiao-Chun , Wang Li-Ju , Tan Yanhao , Chiu Yu-Chiao , Chen Yu-Chih 
Published: September 2024

AbstractTherapy resistance in breast cancer is increasingly attributed to polyploid giant cancer cells (PGCCs), which arise through whole-genome doubling and exhibit heightened resilience to standard treatments. Characterized by enlarged nuclei and increased DNA content, these cells tend to be dormant under therapeutic stress, driving disease relapse. Despite their critical role in resistance, strategies to effectively target PGCCs are limited, largely due to the lack of high-throughput methods for assessing their viability. Traditional assays lack the sensitivity needed to detect PGCC-specific elimination, prompting the development of novel approaches. To address this challenge, we developed a high-throughput single-cell morphological analysis workflow designed to differentiate compounds that selectively inhibit non-PGCCs, PGCCs, or both. Using this method, we screened a library of 2,726 FDA Phase 1-approved drugs, identifying promising anti-PGCC candidates, including proteasome inhibitors, FOXM1, CHK, and macrocyclic lactones. Notably, RNA-Seq analysis of cells treated with the macrocyclic lactone Pyronaridine revealed AXL inhibition as a potential strategy for targeting PGCCs. Although our single-cell morphological analysis pipeline is powerful, empirically testing all existing compounds is impractical and inefficient. To overcome this limitation, we trained a machine learning model to predict anti-PGCC efficacyin silico, integrating chemical fingerprints and compound descriptions from prior publications and databases. The model demonstrated a high correlation with experimental outcomes and predicted efficacious compounds in an expanded library of over 6,000 drugs. Among the top-ranked predictions, we experimentally validated two compounds as potent PGCC inhibitors. These findings underscore the synergistic potential of integrating high-throughput empirical screening with machine learning-based virtual screening to accelerate the discovery of novel therapies, particularly for targeting therapy-resistant PGCCs in breast cancer.
Targeting CCRL2 enhances therapeutic outcomes in a tuberculosis mouse model
Authors: Wang Tianyin , Quijada Darla , Ahmenda Taha , Castillo Jennie Ruelas , Naji Nour Sabiha , Peske J David , Karakousis Petros C. , Paul Suman , Karantanos Theodoros , Karanika Styliani 
Published: September 2024

AbstractTuberculosis (TB) remains among the leading infectious causes of death. Due to the limited number of antimicrobials in the TB drug discovery pipeline, interest has developed in host-directed approaches to improve TB treatment outcomes. C-C motif chemokine-like receptor 2 (CCRL2) is a unique seven-transmembrane domain receptor that is upregulated by inflammatory signals and mediates leucocyte migration. However, little is known about its role in the setting of TB infection. Here, we show thatMycobacterium tuberculosis(Mtb) infection increases CCRL2 protein expression in macrophages and in mouse lungs. To target selectively CCRL2-expressing cellsin vivo,we developed a novel mouse anti-CCRL2 antibody-drug conjugate (ADC) linked with the cytotoxic drug SG3249. We tested its adjunctive therapeutic efficacy against TB when combined with the first-line regimen for drug-susceptible TB (isoniazid, rifampin, pyrazinamide, ethambutol; RHZE). The anti-CCRL2 ADC treatment potentiated RHZE efficacy in Mtb-infected mice and decreased gross lung inflammation. CCRL2 expression in lung dendritic cells and alveolar macrophages was lower in mice receiving anti-CCRL2 ADC treatment + RHZE compared to those receiving RHZE alone or the control group, although the total innate cell populations did not differ across treatment groups. Interestingly, neutrophils were completely absent in the anti-CCRL2 ADC treatment + RHZE group, unlike in the other treatment groups. IFN-γ+ and IL17-Α+ T-cell responses, which are associated with optimal TB control, were also elevated in the anti-CCRL2 ADC treatment + RHZE group. Collectively, our findings suggest that CCRL2-targeting approaches may improve TB treatment outcomes, possibly through selective killing of Mtb-infected innate immune cells.
Perforin-2 is dispensable for host defense againstAspergillus fumigatusandCandida albicans
Authors: Aufiero Mariano A. , Hung Li-Yin , Herbert De’Broski R. , Hohl Tobias M. 
Published: September 2024

ABSTRACTMyeloid phagocytes are essential for antifungal immunity against pulmonaryAspergillus fumigatusand systemicCandida albicansinfections. However, the molecular mechanisms underlying fungal clearance by phagocytes remain incompletely understood. In this study, we investigated the role of perforin-2 (Mpeg1) in antifungal immunity. We found thatMpeg1-/-mice generated on a mixed C57BL/6J-DBA/2 background exhibited enhanced survival, reduced lung fungal burden, and greater neutrophil fungal killing activity compared to wild-type C57BL/6J (B6) mice, suggesting that perforin-2 may impair antifungal immune responses. However, when we comparedMpeg1-/-mice with co-housedMpeg+/+littermate controls, these differences were no longer observed, indicating that initial findings were likely influenced by differences in the murine genetic background or the microbiota composition. Furthermore, perforin-2 was dispensable for antifungal immunity duringC. albicansbloodstream infection. These results suggest that perforin-2 is not essential for host defense against fungal infections in otherwise immune competent mice and highlight the importance of generating co-housed littermate controls to minimize murine genetic and microbiota-related factors in studies of host defense mechanisms.IMPORTANCEAspergillus fumigatusis the leading cause of invasive aspergillosis (IA), which is associated with significant mortality, particularly in immunocompromised patients such as those with acute leukemia or undergoing hematopoietic stem cell transplants, where death rates reach 40-50% despite standard care. Treatments for IA remain limited and resistance to antifungals is emerging, leading the World Health Organization to recently classifyA. fumigatusas a critical priority fungal pathogen. A greater understanding of how the immune system clearsA. fumigatuscould lead to host-directed therapies that could complement our current armamentarium of antifungal drugs and improve patient outcomes. Our findings reveal that perforin-2 is not essential for antifungal immunity againstA. fumigatusin otherwise immune-competent mice and underscore the necessity of using co-housed littermate controls to avoid confounding factors in immunological studies.
Probiotic acoustic biosensors for noninvasive imaging of gut inflammation
Authors: Buss Marjorie T. , Zhu Lian , Kwon Jamie H. , Tabor Jeffrey J. , Shapiro Mikhail G. 
Published: September 2024

ABSTRACTInflammatory bowel diseases (IBD) affect millions of people globally, result in severe symptoms, and are difficult to diagnose and monitor – often necessitating the use of invasive and costly methods such as colonoscopies or endoscopies. Engineered gut bacteria offer a promising alternative due to their ability to persist in the gastrointestinal (GI) tract and sense and respond to specific environmental signals. However, probiotics that have previously been engineered to report on inflammatory and other disease biomarkers in the Gl tract rely on fluorescent or bioluminescent reporters, whose signals cannot be resolved in situ due to the poor penetration of light in tissue. To overcome this limitation, we introduce probiotic biosensors that can be imaged in situ using ultrasound – a widely available, inexpensive imaging modality providing sub-mm spatial resolution deep inside the body. These biosensors are based on the clinically approved probiotic bacteriumE. coliNissle, which we engineered to transiently colonize the GI tract, sense inflammatory biomarkers, and respond by expressing air-filled sound-scattering protein nanostructures called gas vesicles. After optimizing biomolecular signaling circuits to respond sensitively to the biomarkers thiosulfate and tetrathionate and produce strong and stable ultrasound contrast, we validated our living biosensors in vivo by noninvasively imaging antibiotic-induced inflammation in mice. By connecting cell-based diagnostic agents to ultrasound, this “diagnostic yogurt” will make it easier, cheaper, and less painful to diagnose and monitor IBD or other GI conditions.
Application ofhsp60amplicon sequencing to characterize microbial communities associated with juvenile and adultEuprymna scolopessquid
Authors: Smith Steph , Bongrand Clotilde , Lawhorn Susannah , Ruby Edward G. , Septer Alecia N. 
Published: September 2024

AbstractThe symbiotic relationship betweenVibrio (Aliivibrio) fischeriand the Hawaiian bobtail squid,Euprymna scolopes, serves as a key model for understanding host-microbe interactions. Traditional culture-based methods have primarily isolatedV. fischerifrom the light organs of wild-caught squid, yet culture-independent analyses of this symbiotic microbiome remain limited. This study aims to enhance species-level resolution of bacterial communities associated withE. scolopesusinghsp60amplicon sequencing. We validated ourhsp60sequencing approach using pure cultures and mixed bacterial populations, demonstrating its ability to distinguishV. fischerifrom other closely-related vibrios and the possibility of using this approach for strain-level diversity with further optimization. This approach was applied to whole-animal juvenile squid exposed to either seawater or a clonalV. fischeriinoculum, as well as ventate samples and light organ cores from wild-caught adults.V. fischeriaccounted for the majority of the identifiable taxa for whole-animal juvenile samples and comprised 94%-99% of amplicon sequence variants (ASVs) for adult light organ core samples, confirming thatV. fischeriis the dominant, if not sole, symbiont typically associated withE. scolopeslight organs. In one ventate sample,V. fischericomprised 82% of reads, indicating the potential for non-invasive community assessments using this approach. Analysis of non-V. fischeriASVs revealed thatBradyrhizobium spp. and other members of the Rhodobacterales order are conserved across juvenile and adult samples. These findings provide insight into the presence of additional microbial associations with the squid host tissue outside of the light organ that have not been previously detected through traditional culture methods.
Mimicking mechanics: A comparison of meat and meat analogs
Authors: St. Pierre Skyler R. , Kuhl Ellen 
Published: September 2024

AbstractThe texture of meat is one of the most important features to mimic when developing meat analogs. Both protein source and processing method impact the texture of the final product. We can distinguish three types of mechanical tests to quantify the textural differences between meat and meat analogs: puncture-type, rheological torsion tests, and classical mechanical tests of tension, compression, and bending. Here we compile the shear force and stiffness values of whole and comminuted meats and meat analogs from the two most popular tests for meat, the Warner-Bratzler shear test and the double-compression texture profile analysis. Our results suggest that, with the right fine-tuning, today’s meat analogs are well capable of mimicking the mechanics of real meat. While Warner-Bratzler shear tests and texture profile analysis provide valuable information about the tenderness and sensory perception of meat, both tests suffer from a lack of standardization, which limits cross-study comparisons. Here we provide guidelines to standardize meat testing and report the meat stiffness as the single most informative mechanical parameter. Collecting big standardized data and sharing them with the community at large could empower researchers to harness the power of generative artificial intelligence to inform the systematic development of meat analogs with desired mechanical properties and functions, taste and sensory perception.