bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuro-Immune Communication at the Core of Craving-Associated Brain Structural Network Reconfiguration in Methamphetamine Users
Authors: Du Yanyao , Zhang Jiaqi , Cao Dan , Yang Wenhan , Li Jin , Li Deying , Song Ming , Yang Zhengyi , Zhang Jun , Jiang Tianzi , Liu Jun 
Published: December 2023

AbstractMethamphetamine (MA) use disorder is a chronic neurotoxic brain disease characterized by a high risk of relapse driven by intense cravings. However, the neurobiological signatures of cravings remain unclear, limiting the effectiveness of various treatment methods. Diffusion MRI (dMRI) scans from 62 MA users and 57 healthy controls (HC) were used in this study. The MA users were longitudinally followed up during their period of long-term abstinence (duration of long-term abstinence: 347.52±99.25 days). We systematically quantified the control ability of each brain region for craving-associated state transitions using network control theory from a causal perspective. Craving-associated structural alterations (CSA) were investigated through multivariate group comparisons and biological relevance analysis. The neural mechanisms underlying CSA were elucidated using transcriptomic and neurochemical analyses. We observed that long-term abstinence-induced structural alterations significantly influenced the state transition energy involved in the cognitive control response to external information, which correlated with changes in craving scores (r∼ 0.35,P<0.01). Our causal network analysis further supported the crucial role of the prefrontal cortex (PFC) in craving mechanisms. Notably, while the PFC is central to the craving, the CSAs were distributed widely across multiple brain regions (PFDR<0.05), with strong alterations in somatomotor regions (PFDR<0.05) and moderate alterations in high-level association networks (PFDR<0.05). Additionally, transcriptomic, chemical compounds, cell-type analyses, and molecular imaging collectively highlight the influence of neuro-immune communication on human craving modulation. Our results offer an integrative, multi-scale perspective on unraveling the neural underpinnings of craving and suggest that neuro-immune signaling may be a promising target for future human addiction therapeutics.
Double-strand breaks in facultative heterochromatin require specific movements and chromatin changes for efficient repair
Authors: Wensveen Marieke R. , Dixit Aditya A. , Colmenares Serafin U. , Janssen Aniek 
Published: December 2023

AbstractDNA double-strand breaks (DSBs) must be properly repaired within diverse chromatin domains to maintain genome stability. Whereas euchromatin has an open structure and is associated with active transcription, facultative heterochromatin is essential to silence developmental genes and forms compact nuclear condensates, called polycomb bodies. Whether the specific chromatin properties of facultative heterochromatin require distinct DSB repair mechanisms remains unknown. Here, we integrate single DSB systems in euchromatin and facultative heterochromatin inDrosophila melanogasterand find that facultative heterochromatic DSBs rapidly move outside polycomb bodies. These DSB movements coincide with a break-proximal reduction in the canonical heterochromatin mark histone H3 Lysine 27 trimethylation (H3K27me3). We demonstrate that DSB movement and loss of H3K27me3 at heterochromatic DSBs both depend on the histone demethylase dUtx. Moreover, loss of dUtx specifically disrupts completion of homologous recombination at heterochromatic DSBs. We conclude that DSBs in facultative heterochromatin require dUtx-mediated loss of H3K27me3 to promote DSB movement and repair.
Higher seed yield through selection for reduced seed shattering in Italian ryegrass (Lolium multiflorumLam.)
Authors: Kiesbauer Jenny , Kölliker Roland , Hug Maria , Sindelar Meril , Schlatter Linda Helene , Ohnmacht Jonathan , Studer Bruno , Grieder Christoph 
Published: December 2023

ABSTRACTSeed shattering, i.e., the loss of seeds at ripening stage shortly before or during seed harvest, is strongly reducing seed yield in Italian ryegrass (Lolium multiflorumLam.). The aim of this study was to evaluate the possibility to reduce seed shattering within breeding germplasm via recurrent phenotypic selection on spaced plants. Starting from a founder population of 300 plants serving as F0population, two cycles of phenotypic selection for high and low seed shattering were applied and compared to randomly selected individuals on spaced plant level and in plot trials. Comparison of the five resulting populations in a spaced plant trial revealed a significant effect of selection, with lowest seed shattering (15.3%) observed in the population selected twice for decreased shattering (15.3%) and highest seed shattering (47.9%) for the population selected twice for increased shattering. The same ranking of the five F2populations was observed in a subsequent trial with sown plots. Thus, using the method presented here, recurrent selection on single spaced plants allows to efficiently reduce seed shattering and, therefore, to increase seed yield in swards.
Testis organ culture system capable of evaluating testicular toxicity
Authors: Hashimoto Kiyoshi , Arakawa Hiroshi , Imamura Rikako , Nishimura Takuya , Kitajima Satoshi , Sato Takuya , Makiyama Kazuhide , Ogawa Takehiko , Yokota Satoshi 
Published: December 2023

ABSTRACTSuccessful treatment of pediatric cancers often results in long-term health complications, including potential effects on fertility. Therefore, assessing the male reproductive toxicity of anti-cancer drug treatments and the potential for recovery is of paramount importance. However,in vivoevaluations are time-intensive and require large numbers of animals. To overcome these constraints, we utilized an innovative organ culture system that supports long-term spermatogenesis by placing the testis tissue between a base agarose gel and a polydimethylsiloxane ceiling, effectively mirroring thein vivotesticular environment. The present study aimed to determine the efficacy of this organ culture system for accurately assessing testicular toxicity induced by cisplatin, using acrosin-green fluorescent protein (GFP) transgenic neonatal mouse testes. The testis fragments were treated with different concentrations of cisplatin-containing medium for 24 hours and incubated in fresh medium for up to 70 days. The changes in tissue volume and GFP fluorescence over time were evaluated to monitor the progression of spermatogenesis, in addition to the corresponding histopathology. Cisplatin treatment caused tissue volume shrinkage and reduced GFP fluorescence in a concentration-dependent manner. Recovery from testicular toxicity was also dependent on the concentration of cisplatin received. The results demonstrated that this novelin vitrosystem can be a faithful replacement for animal experiments to assess the testicular toxicity of anti-cancer drugs and their reversibility, providing a useful method for drug development.Short AbstractAssessing the male reproductive toxicity of anti-cancer drugs and the potential for recovery is of paramount importance, however,in vivoevaluations are time-intensive and require large numbers of animals. We utilized an innovative organ culture system that mirrors thein vivotesticular environment to determine its efficacy in accurately assessing testicular toxicity induced by cisplatin. The results demonstrate that this system can be a faithful replacement for animal experiments to assess the testicular toxicity of anti-cancer drugs and their reversibility.
Beyond BioID: Streptavidin outcompetes antibody fluorescence signals in protein localization and readily visualises targets evading immunofluorescence detection
Authors: Odenwald Johanna , Gabiatti Bernardo , Braune Silke , Shen Siqi , Zoltner Martin , Kramer Susanne 
Published: December 2023

ABSTRACTImmunofluorescence is a common method to localise proteins within their cellular context via fluorophore labelled antibodies and for some applications without alternative. However, some protein targets evade detection due to low protein abundance or accessibility issues. In addition, some imaging methods require a massive reduction in antigen density thus impeding detection of even medium-abundant proteins.Here, we show that the fusion of the target protein to TurboID, a biotin ligase labelling lysine residues in close proximity, and subsequent detection of biotinylation by fluorescent streptavidin offers an “all in one” solution to the above-mentioned restrictions. For a wide range of target proteins tested, the streptavidin signal was significantly stronger than an antibody signal, markedly improving the imaging sensitivity in expansion microscopy and correlative light and electron microscopy, with no loss in resolution. Importantly, proteins within phase-separated regions, such as the central channel of the nuclear pores, the nucleolus or RNA granules, were readily detected with streptavidin, while most antibodies fail to label proteins in these environments. When TurboID is used in tandem with an HA epitope tag, co-probing with streptavidin and anti-HA can be used to map antibody- accessibility to certain cellular regions. As a proof of principle, we mapped antibody access to all trypanosome nuclear pore proteins (NUPs) and found restricted antibody labelling of all FG NUPs of the central channel that are known to be phase-separated, while most non-FG Nups could be labelled. Lastly, we show that streptavidin imaging can resolve dynamic, temporally and spatially distinct sub-complexes and, in specific cases, reveal a history of dynamic protein interaction.In conclusion, streptavidin imaging has major advantages for the detection of lowly abundant or inaccessible proteins and in addition, can provide information on protein interactions and biophysical environment.
Metformin and guanylurea reduce survival, but have limited sublethal effects in larval zebrafish (Danio rerio)
Authors: Williams S. , Thompson W.A. , Masood N. , Birceanu O. , Easwaramoorthy M. , Qiu J. , Wilson J.Y. 
Published: December 2023

AbstractMetformin is the most common first-line oral therapeutic agent used in the treatment of type-2 diabetes, one of the most prevalent chronic diseases in North America. Post excretion, the compound enters wastewater treatment plants where it is partially bio-transformed by bacteria into guanylurea. Both metformin and guanylurea enter freshwater environments in wastewater effluent where they are available for uptake by aquatic biota. However, our understanding of the effects of metformin and guanylurea on aquatic life is limited. We tested the hypothesis that metformin and guanylurea can influence the development of zebrafish (Danio rerio), by assessing morphometrics, cardiac development, energetic state, and behaviour of early larvae. Embryos were exposed to environmentally relevant (0.4, 4, 40 μg·L−1) and supra-environmental (400 and 4000 μg·L−1) concentrations of metformin and guanylurea from the 4-cell stage (3 hours post fertilization; hpf), until first feed (120 hpf). Exposures to 40 μg·L−1and higher of both metformin and guanylurea increased mortality. Metformin delayed hatching at the highest concentration tested (4000 μg·L−1). The incidence of spinal curvature increased with exposure to both chemicals at supra-environmental levels (400 and 4000 μg·L−1for metformin; 400 μg·L−1for guanylurea). Metformin and guanylurea exposure imposed slight bradycardia in early development, but did not alter oxygen consumption, ATP levels, carbohydrate levels, general swimming, light-dark movement, startle response, or thigmotaxis, irrespective of exposure concentration. The results suggest similar and low sensitivities of larval fish to both metformin and guanylurea. Apart from a small increase in mortality, these compounds impart a modest impact to the early-life stages of zebrafish that are largely limited to supra-environmental concentrations.
Neurodevelopmental timing and socio-cognitive development in a prosocial cooperatively breeding primate (Callithrix jacchus)
Authors: Cerrito Paola , Gascon Eduardo , Roberts Angela C. , Sawiak Stephen J. , Burkart Judith M. 
Published: December 2023

AbstractPrimate, and especially human, brain development is experience-dependent: it is shaped by the inputs received during critical periods. During early development, these inputs systematically differ between independently and cooperatively breeding species, because in cooperative breeders infants are interacting from birth with multiple caretakers and have to thrive in a richer and more challenging social environment. Here, we study the neurodevelopmental timing of the cooperatively breeding common marmoset and how it maps onto behavioral and developmental milestones. To obtain meaningful correlations of structure-function co-constructions, we combine behavioral, imaging (anatomical and functional) and neural tracing experiments. We focus on brain areas that are critically involved when observing conspecifics interacting with others and find that (i) these areas develop in clusters; (ii) these areas reach their maximum gray matter volume shortly after peak provisioning, when immatures are intensely provisioned by group members; (iii) the differentiation of these areas coincides with the period of intense negotiation between immatures and multiple adults over food, the birth of the next set of siblings, and the task of becoming a helper. Moreover, like in humans, differentiation is not fully completed at the age of first reproduction. In sum, we find that the developmental timing of social brain areas coincides with key social and developmental milestones in marmosets, and extends into early adulthood. This rich social input is likely critical for the emergence of the particularly strong prosociality and socio-cognitive skills of marmosets. Since humans are cooperative breeders too, these findings have strong implications for the evolution of human social cognition.
pan-MHC and cross-Species Prediction of T Cell Receptor-Antigen Binding
Authors: Han Yi , Yang Yuqiu , Tian Yanhua , Fattah Farjana J. , Itzstein Mitchell S. von , Hu Yifei , Zhang Minying , Kang Xiongbin , Yang Donghan M. , Liu Jialiang , Xue Yaming , Liang Chaoying , Raman Indu , Zhu Chengsong , Xiao Olivia , Dowell Jonathan E. , Homsi Jade , Rashdan Sawsan , Yang Shengjie , Gwin Mary E. , Hsiehchen David , Gloria-McCutchen Yvonne , Pan Ke , Wu Fangjiang , Gibbons Don , Wang Xinlei , Yee Cassian , Huang Junzhou , Reuben Alexandre , Cheng Chao , Zhang Jianjun , Gerber David E. , Wang Tao 
Published: December 2023

SUMMARYProfiling the binding of T cell receptors (TCRs) of T cells to antigenic peptides presented by MHC proteins is one of the most important unsolved problems in modern immunology. Experimental methods to probe TCR-antigen interactions are slow, labor-intensive, costly, and yield moderate throughput. To address this problem, we developed pMTnet-omni, an Artificial Intelligence (AI) system based on hybrid protein sequence and structure information, to predict the pairing of TCRs of αβ T cells with peptide-MHC complexes (pMHCs). pMTnet-omni is capable of handling peptides presented by both class I and II pMHCs, and capable of handling both human and mouse TCR-pMHC pairs, through information sharing enabled this hybrid design. pMTnet-omni achieves a high overall Area Under the Curve of Receiver Operator Characteristics (AUROC) of 0.888, which surpasses competing tools by a large margin. We showed that pMTnet-omni can distinguish binding affinity of TCRs with similar sequences. Across a range of datasets from various biological contexts, pMTnet-omni characterized the longitudinal evolution and spatial heterogeneity of TCR-pMHC interactions and their functional impact. We successfully developed a biomarker based on pMTnet-omni for predicting immune-related adverse events of immune checkpoint inhibitor (ICI) treatment in a cohort of 57 ICI-treated patients. pMTnet-omni represents a major advance towards developing a clinically usable AI system for TCR-pMHC pairing prediction that can aid the design and implementation of TCR-based immunotherapeutics.
Characterization of methods for mechanistic inference of the gut microbiome in disease
Authors: Santangelo Brook , Hunter Lawrence , Lozupone Catherine 
Published: December 2023

AbstractMotivationKnowledge graphs have found broad biomedical applications, providing useful representations of complex knowledge. Although plentiful evidence exists linking the gut microbiome to disease, mechanistic understanding of those relationships remains generally elusive. A structured analysis of existing resources is necessary to characterize the resources and methodologies needed to facilitate mechanistic inference.ResultsHere we demonstrate the potential of knowledge graphs to hypothesize plausible mechanistic accounts of host-microbe interactions in disease and define the need for semantic constraint in doing so. We constructed a knowledge graph of linked microbes, genes and metabolites called MGMLink, and one of microbial traits, environments, and human pheno-types called KG-microbe-phenio. Using a shortest path search and a pattern based semantically constrained path search through the graphs, we highlight the need for a microbiome-disease resource and semantically informed search methods to enable mechanistic inference.AvailabilityThe software to create MGMLink is openly available athttps://github.com/bsantan/MGMLink, and KG-microbe is available athttps://github.com/Knowledge-Graph-Hub/kg-microbeand KG-phenio is available athttps://github.com/Knowledge-Graph-Hub/kg-phenio.Contactbrook.santangelo@cuanschutz.edu
Strain-specific evolution and host-specific regulation of transposable elements in the model plant symbiontRhizophagus irregularis
Authors: Oliveira Jordana Inácio Nascimento , Corradi Nicolas 
Published: December 2023

AbstractTransposable elements (TE) are repetitive DNA that can create variability in genome structure and regulation. The genome ofRhizophagus irregularis, a widely studied arbuscular mycorrhizal fungus (AMF), comprises approximately 50% repetitive sequences that include transposable elements (TE). Despite their abundance, two-thirds of TE remain unclassified, and their regulation among AMF life-stages remains unknown. Here, we aimed to improve our understanding of TE diversity and regulation in this model species by curating repeat datasets obtained from chromosome-level assemblies and by investigating their expression across multiple conditions. Our analyses uncovered new TE superfamilies and families in this model symbiont and revealed significant differences in how these sequences evolve both within and betweenR. irregularisgenomes. With this curated TE annotation, we detected that the number of upregulated TE families in colonized roots is four times higher than extraradical mycelium, and their overall expression differs depending on their host. This work provides a fine-scale view of TE diversity and evolution in model plant symbionts and highlights their transcriptional dynamism and specificity during host-microbe interactions. We also provide Hidden Markov Model profiles of TE domains are now available for future manual curation of uncharacterized sequences (https://github.com/jordana-olive/TE-manual-curation/tree/main).
UBE2N is essential for maintenance of skin homeostasis and suppression of inflammation
Authors: Lee Min Jin , Ben Hammouda Manel , Miao Wanying , Okafor Arinze , Jin Yingai , Sun Huiying , Jain Vaibhav , Markovtsov Vadim , Diao Yarui , Gregory Simon G. , Zhang Jennifer Y. 
Published: December 2023

ABSTRACTUBE2N, a Lys63-ubiquitin conjugating enzyme, plays critical roles in embryogenesis and immune system development and function. However, its roles in adult epithelial tissue homeostasis and pathogenesis are unclear. We generated conditional mouse models that deletedUbe2nin skin cells in a temporally and spatially controlled manner. We found thatUbe2n-knockout (KO) in the adult skin keratinocytes induced a range of inflammatory skin defects characteristic of psoriatic and actinic keratosis. These included eczematous inflammation, epidermal and dermal thickening, parakeratosis, and increased immune cell infiltration, as well as signs of edema and blistering. Single cell transcriptomic analyses and RT-qPCR showed thatUbe2nKO keratinocytes expressed elevated myeloid cell chemo-attractants such asCxcl1andCxcl2and decreased the homeostatic T lymphocyte chemo-attractant,Ccl27a. Consistently, the infiltrating immune cells ofUbe2n-KO skin were predominantly myeloid-derived cells including neutrophils and M1-like macrophages that were highly inflammatory, as indicated by expression ofIl1βandIl24.Pharmacological blockade of the IL-1 receptor associated kinases (IRAK1/4) alleviated eczema, epidermal and dermal thickening, and immune infiltration of theUbe2nmutant skin. Together, these findings highlight a key role of keratinocyte-UBE2N in maintenance of epidermal homeostasis and skin immunity and identify IRAK1/4 as potential therapeutic target for inflammatory skin disorders.
Power-law growth models explain incidences and sizes of pancreatic cancer precursor lesions and confirm spatial genomic findings
Authors: Kiemen Ashley L. , Wu Pei-Hsun , Braxton Alicia M. , Cornish Toby C. , Hruban Ralph H. , Wood Laura , Wirtz Denis , Zwicker David 
Published: December 2023

AbstractPancreatic ductal adenocarcinoma is a rare but lethal cancer. Recent evidence reveals that pancreatic intraepithelial neoplasms (PanINs), the microscopic precursor lesions in the pancreatic ducts that can give rise to invasive pancreatic cancer, are significantly larger and more prevalent than previously believed. Better understanding of the growth law dynamics of PanINs may improve our ability to understand how a miniscule fraction of these lesions makes the transition to invasive cancer. Here, using artificial intelligence (AI)-based three-dimensional (3D) tissue mapping method, we measured the volumes of >1,000 PanIN and found that lesion size is distributed according to a power law with a fitted exponent of -1.7 over > 3 orders of magnitude. Our data also suggest that PanIN growth is not very sensitive to the pancreatic microenvironment or an individual’s age, family history, and lifestyle, and is rather shaped by general growth behavior. We analyze several models of PanIN growth and fit the predicted size distributions to the observed data. The best fitting models suggest that both intraductal spread of PanIN lesions and fusing of multiple lesions into large, highly branched structures drive PanIN growth patterns. This work lays the groundwork for future mathematical modeling efforts integrating PanIN incidence, morphology, genomic, and transcriptomic features to understand pancreas tumorigenesis, and demonstrates the utility of combining experimental measurement of human tissues with dynamic modeling for understanding cancer tumorigenesis.