bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative genomics of the sexually transmitted parasiteTrichomonas vaginalisreveals relaxed and convergent evolution and genes involved in spillover from birds to humans
Authors: Sullivan Steven A. , Orosco Jordan C. , Callejas-Hernández Francisco , Blow Frances , Lee Hayan , Ranallo-Benavidez Timothy , Peters Andrew , Raidal Shane , Girard Yvette A. , Johnson Christine K. , Rogers Krysta , Gerhold Richard , Mangelson Hayley , Liachko Ivan , Srivastava Harsh , Chandler Chris , Berenberg Daniel , Bonneau Richard A. , Huang Po-Jung , Yeh Yuan-Ming , Lee Chi-Ching , Liu Hsuan , Tang Petrus , Chen Ting-Wen , Schatz Michael C. , Carlton Jane M. 
Published: December 2024

AbstractTrichomonas vaginalisis the causative agent of the venereal disease trichomoniasis which infects men and women globally and is associated with serious outcomes during pregnancy and cancers of the human reproductive tract. Trichomonads parasitize a range of hosts in addition to humans including birds, livestock, and domesticated animals. Recent genetic analysis of trichomonads recovered from columbid birds has provided evidence that these parasite species undergo frequent host-switching, and that a current epoch spillover event from columbids likely gave rise toT. vaginalisin humans. We undertook a comparative evolutionary genomics study of seven trichomonad species, generating chromosome-scale reference genomes forT. vaginalisand its avian sister speciesTrichomonas stableri, and assemblies of five other species that infect birds and mammals. Human-infecting trichomonad lineages have undergone recent and convergent genome size expansions compared to their avian sister species, and the major contributor to their increased genome size is increased repeat expansions, especially multicopy gene families and transposable elements, with genetic drift likely a driver due to relaxed selection. Trichomonads have independently host-switched twice from birds to humans, and genes implicated in the transition to the human host include those associated with host tissue adherence and phagocytosis, extracellular vesicles, and CAZyme virulence factors.
Characterizing postoperative T and B cell dysfunction in cancer surgery patients, using COVID-19 as a model antigen
Authors: Olanubi Oladunni , Dion Taylor , Macdonald Regan , Alam Rafeah , De Souza Christiano Tanese , Hu Richard , Crawley Angela , Auer Rebecca C 
Published: December 2024

AbstractFor most cancers, surgery is an effective intervention method for cure but, despite the benefits, many patients recur with metastatic disease. Surgery has been shown to impair immune function by causing suppression of immune cells. In this study, we used a COVID-19 immunological toolkit to answer questions regarding the effects of surgery on antigen specific CD8+T cells and B cells by exploiting the responses to the spike protein in vaccinated cancer patients. We demonstrate that surgical stress results in a reduction in the number of CD8+T cell that produce cytokines and B cells that secrete antibodies in response to antigen. This study will improve our understanding of surgery-induced T cell and B cell dysfunction
Candidate imprinting control regions in dog genome
Authors: Wyss Phillip , Bina Minou 
Published: December 2024

ABSTRACTIn mammals, genomic imprinting restricts the expression of a subset of genes from one of the two parental alleles. The process is regulated by imprinting control regions (ICRs) and gDMRs (germline Differentially Methylated Regions) dispersed across autosomal chromosomal DNA. An unresolved question is how to discover candidate ICRs in canine DNA genome-wide. Previously, bioinformatics analyses found a significant fraction of well-known ICRs/gDMRs in mouse, human, andBos taurus. Analyses were based on finding the genomic positions of clusters of several CpG-rich motifs known as ZFBS-morph overlaps. These motifs are composite DNA elements. For this report, we performed similar studies to pinpoint candidate ICRs in the dog genome. A key feature of the bioinformatics strategy is creating density plots to mark cluster positions. In genome-wide analyses, peaks in plots effectively discovered candidate ICRs along chromosomal DNA sequences ofCanis lupus familiarisbreed Boxer. With respect to Non-Dog RefSeq Genes, several candidate ICRs are in regions analogous to ICR positions in mouse DNA, in human DNA, or both. In Boxer genome, examples include candidate ICRs for parent-of-origin-specific expression of theMESTisoformPEG1, INPP5F_V2, thePLAGL1isoformZAC1, IGF2R, PEG3, andGNASloci. In mouse, imprinted genes in these loci play important roles in developmental and physiological processes.
Single-Cell Profiling Reveals Global Immune Responses during the Progression of Murine Epidermal Neoplasms
Authors: Fan Xiying , Brunetti Tonya M. , Jackson Kelsey , Roop Dennis R. 
Published: December 2024

AbstractImmune cells determine the role of the tumor microenvironment during tumor progression, either suppressing tumor formation or promoting tumorigenesis. We analyzed the profile of immune cells in the tumor microenvironment of control mouse skins and skin tumors at the single-cell level. We identified 15 CD45+immune cell clusters, which broadly represent the most functionally characterized immune cell types including macrophages, Langerhans cells (LC), conventional type 1 dendritic cells (cDC1), conventional type 2 dendritic cells (cDC2), migratory/mature dendritic cells (mDC), dendritic epidermal T cells (DETC), dermal γδ T cells (γδT), T cells, regulatory T cells (Tregs), natural killer cells (NK), type 2 innate lymphoid cells (ILC2), neutrophils (Neu), mast cells (Mast), and two proliferating populations (Prolif.1 and Prolif.2). Skin tumor progression reprogramed immune cells and led to a marked increase in the relative percentages of macrophages, cDC2, mDC, Tregs, and Neu. Macrophages, the largest cell cluster of immune cells in skin tumors. In addition, macrophages emerged as the predominant communication ‘hub’ in skin tumors, highlighting the importance of macrophages during skin tumor progression. In contrast, other immune cell clusters decreased during skin tumor progression, including DETC, γδT, ILC2, and LC. In addition, skin tumor progression dramatically upregulated Jak2/Stat3 expression and the interferon response across various immune cell clusters. Further, skin tumor progression activated T cells and NK cells indicated by elevated expression of IFN-γ and Granzyme B in skin tumors. Meanwhile, a pronounced infiltration of M2-macrophages and Tregs in skin tumors created an immunosuppressive microenvironment, consistent with the elevated expression of the Stat3 pathway in skin tumors. In summary, our study elucidates the immune cell landscape of epidermal neoplasms, offering a comprehensive understanding of the immune response during skin tumor progression and providing new insights into cancer immune evasion mechanisms.
Engineering tissue-mimetic hydrogels with continuous viscoelastic gradient for programmed cell migration
Authors: Yang Haochen , Li Ziyuan , Li Meng , Shang Yuxing , Chen Linjie , Ge Yifan , Zhang Junji , Tian He 
Published: December 2024

AbstractThe dynamic, viscoelastic nature of the extracellular matrix (ECM), with variations in stiffness and viscosity, plays a key role in cellular behaviors like mechano-sensing, migration, and force generation. Viscoelastic hydrogels are important for mimicking the ECM to study cell migration and tissue engineering. However, creating hydrogels with continuous viscoelastic gradients is challenging due to issues with spatial resolution, reproducibility, and accurately replicating native tissue properties. Here we present a novel approach to generate hydrogels with precisely controllable viscoelastic gradients using drop-by-drop condensation. This approach allows fine-tuned replication of the tissue-specific local mechanical properties, resulting in hydrogels of heterogeneous viscoelasticity. Directed migration and separation of multiple cell lines are thus driven by local viscosity and elasticity rather than solely stiffness. By incorporating non-linear mechanical gradients, this technique provides insights into ECM viscoelasticity’s role in cellular behavior and offers a versatile platform for advanced tissue engineering and regenerative medicine applications.
NECTIN-4 PET FOR OPTIMIZING ENFORTUMAB VEDOTIN DOSE-RESPONSE IN UROTHELIAL CARCINOMA
Authors: Mishra Akhilesh , Sharma Ajay Kumar , Gupta Kuldeep , Banka Dhanush R. , Johnson Burles A. , Hoffman-Censits Jeannie , Huang Peng , McConkey David J. , Nimmagadda Sridhar 
Published: December 2024

ABSTRACTThe optimization of dosing strategies is critical for maximizing efficacy and minimizing toxicity in drug development, particularly for drugs with narrow therapeutic windows such as antibody-drug conjugates (ADCs). This study demonstrates the utility of Nectin-4-targeted positron emission tomography (PET) imaging using [68Ga]AJ647 as a non-invasive tool for real-time assessment of target engagement in enfortumab vedotin (EV) therapy for urothelial carcinoma (UC). By leveraging the specificity of [68Ga]AJ647 for Nectin-4, we quantified dynamic changes in target engagement across preclinical models and established its correlation with therapeutic outcomes. PET imaging revealed dose-dependent variations in Nectin-4 engagement, with suboptimal EV doses resulting in incomplete Nectin-4 engagement and reduced tumor growth. Importantly, target engagement measured by PET emerged as a more reliable predictor of therapeutic efficacy than dose or baseline Nectin-4 expression alone. Receiver operating characteristic (ROC) analysis identified a target engagement threshold that is determinant of response, providing a quantitative benchmark for dose optimization. Furthermore, PET imaging measures provide a promising framework to account for key challenges in ADC development, including tumor heterogeneity, declining drug-to-antibody ratios over time, and limitations of systemic pharmacokinetic measurements to account for tumor-drug interactions. These findings underscore the transformative potential of integrating PET pharmacodynamic measures as early biomarkers to refine dosing strategies, improve patient outcomes, and accelerate the clinical translation of next-generation targeted therapeutics.
Withaferin A downregulates NDRG1 to overcome hypoxia mediated EMT and chemoresistance in lung adenocarcinoma and glioma cells
Authors: Mahajan Divyank , Gandhi Sanchit , Srivastava Tapasya 
Published: December 2024

AbstractOne of the important hurdles to be overcome in the management of cancers is the acquired resistance to therapy. There is a crucial need to not only understand molecular pathways underpinning resistance to therapy but to find better and more effective therapeutic avenues to overcome such acquired resistance. Tumor microenvironmental conditions such as hypoxia have long been known to result in chemoresistance in various cancers that become unresponsive to standard-of-care drugs such as cisplatin. Although many new compounds are screened for their anticancer properties, the recalcitrant tumor microenviroenment has not been given due importance in many potential drugs. In this study, we examine the efficacy of Withaferin A (WA), a bioactive compound isolated fromWithania somnifera, in overcoming hypoxia-induced metabolic adaptation, chemoresistance, and epithelial-to-mesenchymal transition (EMT) in both lung adenocarcinoma and glioma cells. Our results reveal that WA significantly inhibits hypoxia-induced increased migration, EMT, and metabolic reprogramming, leading to enhanced cytotoxicity in otherwise chemoresistant cancer cells. WA treatment suppressed the expression of markers of EMT, glucose metabolism, and bonafide hypoxia markers, particularly NDRG1 thereby inducing cell death in these cancer cells. WA showed significant cytotoxic effects in chemoresistant lung adenocarcinoma and glioma cells, both alone or in combination with cisplatin, highlighting its potential as a therapeutic agent for overcoming chemoresistance in these cancers. Our results provide new insights into the anti-cancer mechanisms of WA especially under hypoxic conditions, and support its further investigation as a promising adjunctive therapy for the treatment against hypoxia-induced chemoresistance in cancers.
Fast and accurate detection of metal resistance genes using MetHMMDb
Authors: Ciuchcinski Karol , Dziurzynski Mikolaj 
Published: December 2024

ABSTRACTHeavy metal pollution poses a major environmental challenge, with microbial resistance to heavy metals offering potential solutions through bioremediation. Additionally, the presence and diversity of microbial metal resistance genes (MMRGs) could contribute to an ecosystem’s ability to adapt and recover from heavy metal contamination by maintaining essential microbial functions and promoting the cycling of nutrients under stress conditions. Thus, MMRGs may serve not only as markers of contamination but also as indicators of an ecosystem’s self-purification capacity and resilience to environmental disturbances. Here we present MetHMMDB, a database containing 254 profile Hidden Markov Models representing 121 MMRGs. Unlike traditional sequence-based resources, MetHMMDB relies on HMMs to improve detection sensitivity and functional specificity across microbial communities. Created through iterative database searches, sequence clustering, structural prediction, and manual annotation, MetHMMDB emphasizes functional annotation rather than gene classification. The database outperforms sequence-based approaches, identifying over twice as many MMRGs in metagenomic datasets, including those from extreme environments. Analysis of agricultural soil revealed distinct resistance profiles correlating with soil quality. MetHMMDB advances our understanding of microbial adaptation to heavy metal contamination while supporting environmental management strategies through improved identification and characterization of metal resistance mechanisms.Database URL:https://github.com/Haelmorn/MetHMMDB.
Pro-cognitive reshaping of neuronal dynamics by a human CSF-based factor
Authors: Santos Marc Dos , Forrest Marc P. , Bomba-Warczak Ewa , Parnell Euan , Edassery Seby L. , Yang Kun , Hayes Lindsay N. , Coughlin Jennifer M. , Eckman Blair L. , Lammert Catherine , Martin-de-Saavedra M. Dolores , Barbolina Maria , Sawa Akira , Savas Jeffrey N. , Penzes Peter 
Published: December 2024

AbstractNeuronal connection dysfunction is a convergent cause of cognitive deficits in mental disorders. Cognitive processes are finely regulated at the synaptic level by membrane proteins, some of which are shed and detectable in patients’ cerebrospinal fluid (CSF). However, whether these soluble synaptic proteins can harnessed as innovative pro-cognitive factors to treat brain disorders remains unclear. Here, we use quantitative proteomics to identify shed synaptic proteins dysregulated in the CSF of subjects with schizophrenia (SCZ), a mental disorder characterized by cognitive and synaptic dysfunction. The level of a yet uncharacterized soluble form of the voltage-gated calcium channel auxiliary subunit, α2δ-1, is robustly reduced in SCZ CSF. Remarkably, soluble α2δ-1 is convergently downregulated across several brain disorder CSF proteomes. We show that the brain releases soluble α2δ-1 in an activity-dependent manner, which can reorganize neuronal network dynamics by binding to synaptic targets and promoting inhibitory neuron plasticity. A single brain injection of a synthetic soluble α2δ-1 improved interneuron and cognitive deficits in a mutant mouse model of SCZ and cortical dysfunction. These findings underscore the potential of shed synaptic proteins as novel therapeutic agents capable of enhancing brain function in diverse brain disorders characterized by cognitive impairment.
A Thermo-responsive collapse system for controlling heterogeneous cell localization, ratio and interaction for three-dimensional solid tumor modeling
Authors: Li Yu , Orange Jordan S. 
Published: December 2024

AbstractCancer immunotherapy using engineered cytotoxic effector cells has demonstrated significant potential. The limited spatial complexity of existingin vitromodels, however, poses a challenge to mechanistic studies attempting to approve existing approaches of effector cell-mediated cytotoxicity within a three-dimensional, solid tumor-like environment. To gain additional experimental control, we developed an approach for constructing three-dimensional (3D) culture models using smart polymers that form temperature responsive hydrogels. By embedding cells in these hydrogels, we constructed 3D models to organize multiple cell populations at specified ratios on- demand and gently position them by exploiting the hydrogel phase transition. These systems were amenable to imaging at low- and high-resolution to evaluate cell-to-cell interactions, as well as to dissociation to allow for single cell analyses. We have called this approach “thermal collapse of strata” (TheCOS) and demonstrated its use in creating complex cell assemblies on demand in both layers and spheroids. As an application, we utilized TheCOS to evaluate the impact of directionality of degranulation of natural killer (NK) cell lytic granules. Blocking lytic granule convergence and polarization by inhibiting dynein has been shown to induce bystander killing in single cell suspensions. Using TheCOS we showed that lytic granule dispersion induced by dynein inhibition can be sustained in 3D and results in a multi-directional killing including that of non-triggering bystander cells. By imaging TheCOS experiments, we were able to map a “kill zone” associated with multi-directional degranulation in simulated solid tumor environments. TheCOS should allow for the testing of approaches to alter the mechanics of cytotoxicity as well as to generate a wide-array of human tumor microenvironments to assist in the acceleration of tumor immunotherapy.
Tumour-derived LAMA5 is critical for tumour initiation and controls progression and phenotype in luminal breast cancer
Authors: Ritchie Alexandra , Dhawan Priyal , Kailari Eveliina , Linden Jere , Blaas Leander , Izzi Valerio , Katajisto Pekka , Englund Johanna I. 
Published: December 2024

ABSTRACTBasement membrane (BM) supports and regulates the structural integrity, function and differentiation of epithelial tissues and protects against stromal invasion of breast cancer cells. Here we show that LAMA5, a central BM component, is critical for luminal mammary tumour initiation, and controls tumor progression and phenotype development. LAMA5 is overexpressed in both human and mouse luminal mammary tumours andLAMA5downregulation attenuates growth of human breast cancer cells. Prepubertal luminal deletion ofLama5in MMTV-PyMT mice results in marked reduction in emergence of early hyperplasias, along with a shift from mature hormone receptor (HR+) positive luminal epithelial phenotype towards a HR+ progenitor phenotype, and widespread alterations in extracellular matrix and Fibroblast growth factor (Fgf) signalling genes, including overexpression of Fgf receptor 2 (Fgfr2) in the HR+ progenitor cells. Single allele deletion, but not biallelic deletion ofLama5additionally inhibits growth and progression towards advanced mammary carcinomas. However, inhibition of Fgf receptors restores growth decrease and induces apoptosis in biallelic-Lama5-deleted organoids without affecting wildtype organoids. Our analyses demonstrate a critical role for a BM component LAMA5 in mammary tumour initiation and reveal mechanisms of extracellular matrix-epithelial interplay in breast tumour progression and phenotype maintenance.
A High-quality Genome Assembly ofAnnona squamosa(Custard Apple) Provides Functional Insights into an Emerging Fruit Crop
Authors: Bisht Manohar S. , Mahajan Shruti , Chakraborty Abhisek , Sharma Vineet K. 
Published: December 2024

AbstractAnnona squamosa, also known as custard apple, is an emerging fruit crop with medicinal significance. We constructed a high-quality genome ofA. squamosaalong with transcriptome data to gain insights into its phylogeny, evolution and demographic history. The genome has an N50 value of 93.2 Mb assembled into seven pseudochromosomes. The demographic history showed a continuous decline in the effective population size ofA. squamosa. Phylogenetic analysis revealed that magnoliids were sister to eudicots, whereas ASTRAL gene trees showed discordance due to incomplete lineage sorting (ILS). Genome syntenic and Ks distribution analyses confirmed the absence of a recent whole genome duplication event in theA. squamosa. Gene families related to photosynthesis, oxidative phosphorylation and plant thermogenesis were found to be highly expanded in the genome. Comparative analysis with other magnoliids revealed the adaptative evolution in the genes of flavonoid biosynthesis pathway, amino sugar, nucleotide sugar and sucrose metabolism, conferring medicinal value and enhanced hexose sugar accumulation. In addition, we performed genome-wide identification ofSWEETgenes. Our high-quality genome and evolutionary insights of this emerging fruit crop, thus, serve as a valuable resource for advancing studies in functional genomics, evolutionary biology, and crop improvement.
Acinetobacter baumannii’s Great Escape: How a Membrane Protein Interacts with Fibronectin to Evade Immunity
Authors: Vasseur Laurine , Barbault Florent , Monari Antonio 
Published: December 2024

ABSTRACTBacterial resistance and nosocomial infections are serious threats compromising public health in numerous countries. Acinetobacter baumannii has been identified as one of the most serious pathogens, due to its potential virulence and the development of multiple resistance. In this contribution by using all-atom molecular dynamics simulation, we analyze the structure and the properties of the OmpA protein, which is present in the bacterial external membrane. We also analyze the structure of possible protein/protein complexes formed between OmpA and the human fibronectin, which may ultimately lead to the immune escaping of the bacteria. For the first time, we provide for the first time plausible structure of the complex also identifying suitable amino acid mediating the interaction, and thus, constituting suitable drug targets to disrupt the complex formation.TOC Abstract