bluuebunny/crossref_metadata_2025_split huggingface dataset:
Admixture and environmental fluctuations shape the evolutionary history of a predator radiation in East Africa’s Lake Tanganyika
Authors: Rick Jessica A. , Junker Julian , Lewanski Alexander L. , Swope Brittany , McGlue Michael M. , Sweke Emmanuel A. , Kimirei Ismael A. , Seehausen Ole , Wagner Catherine E. 
Published: January 2025

AbstractTop predators have oversized impacts on food webs and ecosystem dynamics, and introducing a novel predator to a naive environment can have dramatic consequences for endemic biodiversity. Lake Tanganyika is unique among African lakes in the diversity of the pelagic top predators in the genusLates, where four species are endemic to the lake. Using a combination of reduced-representation and whole genome resequencing data, and pairing these with phylogenetic and demographic modeling approaches, we find thatLatescolonization of Lake Tanganyika was much more recent (∼1–2 Mya) than other major and diverse clades within the lake. Demographic modeling suggests that diversification amongLatesspecies within the lake occurred during a time period of dramatic changes in lake levels driven by glacial-interglacial cycles, supporting a role of these fluctuations as a “species pump” for lacustrine taxa. We further find that these lake level fluctuations likely contributed to multiple bouts of admixture amongLatesspecies during the mid- to late-Pleistocene (∼90–500 Kya). Together, our findings suggest a dynamic and environmentally linked evolutionary history of theLatesradiation with the potential for dramatic ecosystem consequences for the taxa already present in Lake Tanganyika prior toLatescolonization and diversification.Significance StatementWhen introduced to novel ecosystems, top predators can cause major alterations to biodiversity and food webs. Species introductions to novel habitats can also provide invading taxa with ecological opportunities that facilitate evolutionary diversification. Here, we find evidence that the radiation of endemic top predators in East Africa’s Lake Tanganyika originated surprisingly recently, and that these species have experienced periods of hybridization with a widespread riverine relative throughout their history. These findings have major implications for the history of the lake and suggest that the introduction of Nile perch into Lake Victoria, which caused dramatic ecosystem and food web changes, may be a contemporary analog to the historical events in Lake Tanganyika.
Bridging Earth and Space: A Flexible and Resilient Federated Learning Framework Deployed on the International Space Station
Authors: Casaletto James A. , Foley Patrick , Fernandez Mark , Sanders Lauren M. , Scott Ryan T. , Ranjan Shubha , Jain Shashi , Haynes Nate , Boerma Marjan , Costes Sylvain V. , Mackintosh Graham 
Published: January 2025

AbstractThe public and commercial space industries are planning longer duration and more distant space missions, including the establishment of a habitable lunar base and crewed missions to Mars. To support Earth-independent scientific and medical operations, such missions can leverage artificial intelligence and machine learning models to assist with crew healthcare, spacecraft maintenance, and other critical tasks. However, transferring large volumes of data between Earth and space for model development consumes valuable bandwidth, is vulnerable to communication disruptions, and may compromise crew safety and data privacy. Federated learning enables model training while keeping datain situand only transferring model parameters. In this work, we present a flexible, resilient federated learning framework that provides the secure transmission of model updates between Earth and the International Space Station. On March 15, 2024, this framework pioneered the deployment of federated learning in a spaceflight setting, training classifier models between Earth and the ISS using both real biomedical research data and synthetically generated data.
Transcriptomic signature reveals sensitivity to tubulin inhibitors in colon cancer
Authors: Liñares-Blanco Jose , Chicote Irene , Ros Javier , Alcántara Anna M , Martínez-Quintanilla Jordi , Elez Elena , G Palmer Héctor , Fernandez-Lozano Carlos , Seoane Jose A 
Published: January 2025

AbstractColon cancer is the second most common cause of cancer death worldwide. Despite advances in the development of new molecular strategies for stratifying patients with colon cancer, many of these patients do not respond adequately to the standard of care. While previous studies have focused on the development of prognostic gene expression signatures, the exploration of predictive signatures to inform treatment decisions remains incomplete.In this study, we leveraged public gene expression datasets to design and experimentally validate a 37-gene expression signature for prognosis in colon cancer patients. We obtained a C-index of 0.732 (0.610-0.853) in four independent studies. Specifically, we discovered that the signature is associated with the mitotic phase of the cell cycle. Furthermore, the signature identified a population of colon cancer patients sensitive to tubulin inhibitor drugs. In particular, we validatedin vitroandin vivothe efficacy of paclitaxel, a commonly used tubulin inhibitor in breast cancer treatment, in patient-derived preclinical models.These results highlight the importance of incorporating gene expression signatures to identify new therapeutic options for colon cancer treatment. Furthermore, the identification of alternative treatment options with potentially improved efficacy holds promise for the development of new clinical trials, and reshapes the biomarker-based treatment strategy for second line and refractory colon cancer patients.
Fire shifts the structure and dynamics of woody plant communities in a mediterranean coastal dune ecosystem
Authors: Mira André F. , Medina Nagore G. , Chozas Sergio , Divieso Raquel , Castro-Rivadeneyra Juan , Díaz-Barradas Mari Cruz , Hortal Joaquín 
Published: January 2025

AbstractCoastal dune ecosystems are dynamic and fragile environments shaped by complex interactions between vegetation and its characteristic abiotic factors. This study investigates the effects of the wildfire that affected the Doñana Nacional Park (SW Spain) in 2017 on the composition and structure of woody plant communities in two adjacent Mediterranean coastal dune areas: one affected by fire (Cuesta Maneli) and one unburned (Laguna del Jaral). Using a combination of several analyses (such as non-metric multidimensional scaling (NMDS); Mantel tests; and co-occurrence analyses), we examined how fire influences species distribution, abundance, and their interactions along a coastal-inland gradient. Our results reveal that fire homogenizes woody plant community composition across the coastal-inland gradient, reducing spatial differentiation and increasing overall species abundance in the burned area. Soil characteristics influenced species’ composition significantly only in the unburned site, suggesting that fire disrupted abiotic filtering processes. Co-occurrence patterns indicate more neutral interactions in the burned area, consistent with reduced competition and increased resource availability post-disturbance. In contrast, the unburned site displayed structured communities with stronger negative co-occurrence at the smaller scales and spatial clustering of species. Spatial pattern analyses showed that positive co-occurrence was more prevalent in the burned area, particularly at smaller spatial scales, indicating potential facilitation effects during early post-fire recovery. These findings highlight how fire reshapes community structure and dynamics after succession. Understanding these processes is critical for effective conservation and management of Mediterranean coastal dune ecosystems facing increasing anthropogenic pressures and climate change-related disturbances.
Modeling of ATP Transport in an Axon: Effects of Spontaneous Neuron Firing and Mitochondrial Transfer via Tunneling Nanotubes
Authors: Kuznetsov Andrey V. 
Published: January 2025

AbstractWhile electrical activity in neurons has been extensively studied, the transport and distribution of adenosine triphosphate (ATP), the primary cellular energy carrier, remain less understood, particularly in relation to metabolic processes in axons. ATP is primarily generated in mitochondria and consumed at synapses, the primary sites of energy demand. Even in healthy axons, approximately half of synaptic boutons lack stationary mitochondria, raising questions about ATP transport between boutons with and without mitochondrial ATP production. This study addresses two key questions: the role of spontaneous neuronal firing in maintaining ATP levels during periods of low energy demand and the ability of a single bouton with a donated mitochondrion to supply ATP to neighboring boutons lacking mitochondria. Using computational simulations, the study examines ATP transport under various firing patterns and mitochondrial distributions, incorporating factors such as quiescent periods, duty cycles, and ATP diffusivity. Spontaneous neuronal firing stabilizes ATP levels during periods of low energy demand, preventing reactive oxygen species (ROS) release from mitochondria. Simulations reveal that in neurons damaged by neurodegeneration, a single bouton containing a donated mitochondrion can support ATP levels in multiple empty boutons. However, as the number of empty boutons increases, ATP concentration declines, potentially falling below the critical threshold required for synaptic transmission.Nomenclaturea0kinetic constant characterizing the rate of ATP consumption in a boutonAccross-sectional area of the axonCATP concentration per unit length of the axonC0typical value of ATP concentration per unit length of the axonCminminimum ATP concentration required to sustain synaptic transmissiondutyduty cycleDATP diffusivity in the cytosolffrequency at which neuron fires during the active phaseiactivenumber of action potentials that occur during the active phaseitotaltotal number of action potentials that propagate down the axon during the active phase plus the number of action potentials that were missed during the quiescent phaseLdistance between boutonsmATP production rate per unit length of a mitochondrionATP production rate per unit mass of tissueNemptynumber of boutons in the CV that lack stationary mitochondriattimexposition along the axonxmhalf-length of a mitochondrionGreek symbolsγpercentage of tissue volume occupied by mitochondriaδhalf the width of an axonal varicosityϖmass of an individual mitochondrionΛhomeostaticportion of energy expended on homeostatic maintenance of a bouton
Eusociality evolved at a much higher rate in haplodiploid insects
Authors: Suresh Sachin , Linksvayer Timothy A. 
Published: January 2025

AbstractAs a corollary to inclusive fitness theory, W.D. Hamilton’s famous haplodiploid hypothesis proposed that eusociality evolves more readily in haplodiploids because of an inflated genetic relatedness between sisters. For the past sixty years, theoreticians have developed an array of models that further clarify how eusociality might evolve more readily in haplodiploids. Despite this sustained theoretical interest, the predicted evolutionary association between haplodiploidy and eusociality was only recently empirically tested when a family-level analysis in insects found mixed support. Here, we use a large species-level insect phylogeny with all available sociality and ploidy trait data to test whether there is an evolutionary association between haplodiploidy and eusociality. We show that the transition rate from solitary to eusocial life was 15-100 times higher in haplodiploid than diploid lineages, depending on the definitions of eusociality and haplodiploidy. Our results strongly support the prediction of the haplodiploid hypothesis and related models that the evolutionary transition from solitary to eusocial life is facilitated by haplodiploidy.Significance statementSixty years ago, Hamilton hypothesized that eusociality evolves more readily in haplodiploid populations due to inflated relatedness among sisters. This haplodiploid hypothesis is often presented as a textbook example of how inclusive fitness theory can explain the phylogenetic distribution of eusociality across the tree of life. Theoreticians soon noted flaws in Hamilton’s original formulation but have developed more models, still predicting that haplodiploidy facilitates the evolution of eusociality. Despite these theoretical predictions, most researchers have long doubted any phylogenetic association between haplodiploidy and eusociality. We tested this association using a large species-level insect phylogeny with all the available trait data. Our results show that eusociality evolved at a much higher rate in haplodiploids, conclusively supporting the predicted association.
Temperature vaulting: A method for screening of slow- and tight-binding inhibitors that selectively target kinases in their non-native state
Authors: Suzuki Sora , Umezawa Koji , Furuie Gaku , Kikuchi Masaki , Nakamura Daichi G. M. , Fukahori Nanae , Kimura Ninako , Yamakawa Masato , Niwa Takashi , Umehara Takashi , Hosoya Takamitsu , Kii Isao 
Published: January 2025

ABSTRACTA polypeptide folds into its protein tertiary structure in the native state through a folding intermediate in the non-native state. The transition between these states is thermodynamically driven. A folding intermediate of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) autophosphorylates intramolecularly, whereas DYRK1A in the native state no longer catalyzes this reaction. The alteration in substrate specificity suggests a conformational transition of DYRK1A during its folding process. Consistent with this hypothesis, we identified FINDY (1), which inhibits the intramolecular autophosphorylation but not the intermolecular phosphorylation, suggesting that the folding intermediate possesses an alternative inhibitor-binding site. Meanwhile, it remains an issue that the methods for approaching the alternative binding site require an intricate assay tailored to the individual target. Here we show a method, designated as “temperature vaulting,” for screening the non-native-state-targeted inhibitors of DYRK1A. Transient heating of recombinant DYRK1A protein drove the reversible transition between the native state and the non-native state targeted by FINDY (1). At physiological temperature, FINDY (1) slowly bound to the DYRK1A protein. These results indicate that transient heating accelerates the slow-binding process by assisting the protein to overcome the high-energy barrier leading to the target non-native state. The energy barrier also slowed down the dissociation process, resulting in tight binding between DYRK1A and FINDY (1). Furthermore, this study suggests that the dissociation rate underlies the inhibition selectivity of FINDY (1) between DYRK1A and its family kinase DYRK1B. This method enables the identification of slow- and tight-binding inhibitors that have been missed in conventional assays.HIGHLIGHTSA temperature vaulting method facilitated the screening of a slow- and tight-binding inhibitor targeting DYRK1A in the non-native state.A structure–activity relationship study of FINDY (1) demonstrated that a slight alteration in chemical structure impacts the inhibition kinetics.A molecular dynamics simulation of DYRK1A revealed binding-ready conformations for FINDY (1).The dissociation rate may underlie the inhibition selectivity of FINDY (1) between DYRK1A and DYRK1B in cellular systems.
Gene family evolution reveals dietary adaptations in butterflies and moths
Authors: Weng Yi-Ming , Martinez Jose I. , Markee Amanda , Plotkin David , Sondhi Yash , Mongue Andrew J. , Frandsen Paul B. , Kawahara Akito Y. 
Published: January 2025

AbstractButterflies and moths (Lepidoptera) are a hyperdiverse lineage of nearly 160,000 described species and their evolutionary success is postulated to be tightly correlated with the radiation of their primary host — angiosperms. Previous studies found that a significant number of emergent gene families are specific to Lepidoptera, with many genes linked to odorant receptors and peptidases, suggesting that such genetic innovations may be linked to their diversification. Here, we use genomic resources to identify lineage-specific gene families in four nested lepidopteran clades (e.g. Lepidoptera, Glossata, Ditrysia, and Apoditrysia). Among nearly a hundred gene families specific to each group, a handful of gene families have specific and interpretable functions. We found that many digestion-related gene families emerged early in the evolution of Lepidoptera, followed by genes associated with detoxification and immunity. This result aligns with the evolutionary transition in ancient Lepidoptera diets to terrestrial plants, highlighting the emergence of detoxification mechanisms in the megadiverse Ditrysia as a critical adaptation driven by the proliferation of plant chemical defenses. We also found gene families originating from horizontal gene transfer (HGT) events, likely introduced from bacteria and fungi to the common ancestors of Lepidoptera and Ditrysia, respectively. These HGT-derived genes likely played a pivotal role in supporting the dietary transition from algae, diatoms, and aquatic plant debris to fungi and primitive terrestrial plants, ultimately enabling the adaptation to the most dominant angiosperm species.
IL-9 as a naturally orthogonal cytokine with optimal JAK/STAT signaling for engineered T cell therapy
Authors: Jiang Hua , Limsuwannarot Sam , Kulhanek Kayla R. , Pal Aastha , Rysavy Lea W. , Su Leon , Labiad Ossama , Testa Stefano , Ogana Heather , Waghray Deepa , Tao Pingdong , Jude Kevin M. , Seet Christopher S. , Crooks Gay M. , Moding Everett J. , Christopher Garcia K. , Kalbasi Anusha 
Published: January 2025

SUMMARYArming T cells with a synthetically orthogonal IL-9 receptor (o9R) permits facile engraftment and potent anti-tumor functions. We considered whether the paucity of natural IL-9R expression could be exploited for T cell immunotherapy given that, in mice, high doses of IL-9 were well-tolerated without discernible immune modulation. Compared to o9R, T cells engineered with IL-9R exhibit superior tissue infiltration, stemness, and anti-tumor activity. These qualities are consistent with a stronger JAK/STAT signal, which in addition to STAT1/3/5, unexpectedly includes STAT4 (canonically associated with IL-12 but not common γ-chain cytokines). IL-9R T cells are exquisitely sensitive to perturbations of proximal signaling, including structure-guided attenuation, amplification, and rebalancing of JAK/STAT signals. Biased IL-9R mutants uncover STAT1 as a rheostat between proliferative stem-like and terminally differentiated effector states. In summary, we identify native IL-9/IL-9R as a natural cytokine-receptor pair with near-orthogonal qualities and an optimal JAK/STAT signaling profile for engineered T cell therapy.
Synthetic inhibition of the SUMO pathway by targeting the SAE1 component via TAK-981 compound impairs tumor growth and chemosensitizers embryonal and alveolar rhabdomyosarcoma cell lines
Authors: Codenotti Silvia , Lauschke Volker M. , Casella Emma V. , Andersson Daniel C. , Fanzani Alessandro , Gastaldello Stefano 
Published: January 2025

AbstractBackgroundRhabdomyosarcoma (RMS) is a highly aggressive pediatric soft tissue sarcoma with limited therapeutic options, particularly for cases resistant to conventional treatments. The SUMOylation pathway, which plays a key role in regulating cell cycle, apoptosis, and transcription, has emerged as a potential therapeutic target in RMS. Elevated levels of SUMO1 and SUMO2/3 conjugates in RMS cell lines, compared to normal human skeletal muscle cells, underscore the association between hyper-SUMOylation and aggressive cancer phenotypes. Understanding these molecular underpinnings is critical for the development of innovative and effective treatments.MethodsThe investigation encompassed transcriptomic and protein analyses to profile SUMOylation pathway components across alveolar and embryonal RMS subtypes, aiming to identify heterogeneity that could guide personalized therapy approaches. TAK-981’s interactions with chemotherapeutic agents, were evaluated for synergistic effects. Additionally, its impact on radiosensitivity and key signaling pathways, such as AKT and ERK phosphorylation, was assessed to elucidate its mechanism of action.ResultsTranscriptomic and proteomic analyses revealed distinct expression profiles of SUMOylation pathway components across RMS subtypes, highlighting heterogeneity that could guide personalized therapeutic strategies. Notably, SAE1 protein was overexpressed in RMS tissues and cells, positioning it as a potential biomarker for this cancer. Its activity was effectively counteracted by TAK-981, a SUMO inhibitor that demonstrated significant therapeutic potential by suppressing RMS cell proliferation and migration and enhancing the cytotoxic effects of chemotherapeutic agents, actinomycin D and doxorubicin. However, TAK-981 did not increase radiosensitivity, suggesting its selective action through chemical inhibition mechanisms. Mechanistically, TAK-981 reduced phosphorylation of key signaling proteins, including AKT and ERK, critical for RMS cell survival.ConclusionThe findings of this study establish TAK-981 as a promising therapeutic agent for RMS. The results also provide foundational insights into the role of SUMOylation associated to the new biomarker SAE1 in RMS and its subtypes, paving the way for the development of personalized treatment strategies that leverage SUMO pathway inhibition.
Tumor suppressor genotype influences the extent and mode of immunosurveillance in lung cancer
Authors: Adler Keren M. , Xu Haiqing , Gladstein Amy C. , Irizarry-Negron Valerie M. , Robertson Maggie R. , Doerig Katherine R. , Petrov Dmitri A. , Winslow Monte M. , Feldser David M. 
Published: January 2025

AbstractThe impact of cancer driving mutations in regulating immunosurveillance throughout tumor development remains poorly understood. To better understand the contribution of tumor genotype to immunosurveillance, we generated and validated lentiviral vectors that create an epi-allelic series of increasingly immunogenic neoantigens. This vector system is compatible with autochthonous Cre-regulated cancer models, CRISPR/Cas9-mediated somatic genome editing, and tumor barcoding. Here, we show that in the context of KRAS-driven lung cancer and strong neoantigen expression, tumor suppressor genotype dictates the degree of immune cell recruitment, positive selection of tumors with neoantigen silencing, and tumor outgrowth. By quantifying the impact of 11 commonly inactivated tumor suppressor genes on tumor growth across neoantigenic contexts, we show that the growth promoting effects of tumor suppressor gene inactivation correlate with increasing sensitivity to immunosurveillance. Importantly, specific genotypes dramatically increase or decrease sensitivity to immunosurveillance independently of their growth promoting effects. We propose a model of immunoediting in which tumor suppressor gene inactivation works in tandem with neoantigen expression to shape tumor immunosurveillance and immunoediting such that the same neoantigens uniquely modulate tumor immunoediting depending on the genetic context.One Sentence SummaryHere we uncover an under-appreciated role for tumor suppressor gene inactivation in shaping immunoediting upon neoantigen expression.