bluuebunny/crossref_metadata_2025_split huggingface dataset:
A chimeric vaccine protects farmed saltwater crocodiles from West Nile virus-induced skin lesions
Authors: Habarugira Gervais , Harrison Jessica J. , Moran Jasmin , Suen Willy W. , Colmant Agathe M. G. , Hobson-Peters Jody , Isberg Sally R. , Bielefeldt-Ohmann Helle , Hall Roy A. 
Published: June 2023

AbstractWest Nile virus (WNV) causes skin lesions in farmed crocodiles leading to the depreciation of the value of their hides and significant economic losses. However, there is no commercially available vaccine designed for use in crocodilians against WNV. We tested chimeric virus vaccines composed of the non-structural genes of the insect-specific flavivirus Binjari virus (BinJV) and genes encoding the structural proteins of WNV. The BinJV/WNV chimera, is antigenically similar to wild-type WNV but replication-defective in vertebrates. Intramuscular injection of two doses of BinJV/WNV in hatchling saltwater crocodiles (Crocodylus porosus) elicited a robust neutralising antibody response and conferred protection against viremia and skin lesions after challenge with WNV. In contrast, mock-vaccinated crocodiles became viraemic and 22.2% exhibited WNV-induced lesions. This suggests that the BinJV/WNV chimera is a safe and efficacious vaccine for preventing WNV-induced skin lesions in farmed crocodilians.
Self-patterning of human stem cells into post-implantation lineages
Authors: Pedroza Monique , Gassaloglu Seher Ipek , Dias Nicolas , Zhong Liangwen , Hou Tien-Chi Jason , Kretzmer Helene , Smith Zachary D. , Sozen Berna 
Published: June 2023

AbstractInvestigating human development is a substantial scientific challenge due to the technical and ethical limitations of working with embryonic samples. In the face of these difficulties, stem cells have provided an alternative to experimentally model inaccessible stages of human development in vitro1–13. Here we show that human pluripotent stem cells can be triggered to self-organize into three-dimensional structures that recapitulate some key spatiotemporal events of early human post-implantation embryonic development. Our system reproducibly captures spontaneous differentiation and co-development of embryonic epiblast-like and extra-embryonic hypoblast-like lineages, establishes key signalling hubs with secreted modulators and undergoes symmetry breaking-like events. Single-cell transcriptomics confirms differentiation into diverse cell states of the perigastrulating human embryo14,15 without establishing placental cell types, including signatures of post-implantation epiblast, amniotic ectoderm, primitive streak, mesoderm, early extra-embryonic endoderm, as well as initial yolk sac induction. Collectively, our system captures key features of human embryonic development spanning from Carnegie stage16 4–7, offering a reproducible, tractable and scalable experimental platform to understand the basic cellular and molecular mechanisms that underlie human development, including new opportunities to dissect congenital pathologies with high throughput.
Pluripotent stem cell-derived model of the post-implantation human embryo
Authors: Weatherbee Bailey A. T. , Gantner Carlos W. , Iwamoto-Stohl Lisa K. , Daza Riza M. , Hamazaki Nobuhiko , Shendure Jay , Zernicka-Goetz Magdalena 
Published: June 2023

AbstractThe human embryo undergoes morphogenetic transformations following implantation into the uterus, but our knowledge of this crucial stage is limited by the inability to observe the embryo in vivo. Models of the embryo derived from stem cells are important tools for interrogating developmental events and tissue–tissue crosstalk during these stages1. Here we establish a model of the human post-implantation embryo, a human embryoid, comprising embryonic and extraembryonic tissues. We combine two types of extraembryonic-like cell generated by overexpression of transcription factors with wild-type embryonic stem cells and promote their self-organization into structures that mimic several aspects of the post-implantation human embryo. These self-organized aggregates contain a pluripotent epiblast-like domain surrounded by extraembryonic-like tissues. Our functional studies demonstrate that the epiblast-like domain robustly differentiates into amnion, extraembryonic mesenchyme and primordial germ cell-like cells in response to bone morphogenetic protein cues. In addition, we identify an inhibitory role for SOX17 in the specification of anterior hypoblast-like cells2. Modulation of the subpopulations in the hypoblast-like compartment demonstrates that extraembryonic-like cells influence epiblast-like domain differentiation, highlighting functional tissue–tissue crosstalk. In conclusion, we present a modular, tractable, integrated3 model of the human embryo that will enable us to probe key questions of human post-implantation development, a critical window during which substantial numbers of pregnancies fail.
Effects of porous structure on the deformation failure mechanism of cement sheaths for wellbores
Authors: Yang Yongming , Li Xiwen , Sun Mengke , Ju Yang 
Published: June 2023

AbstractThe influence and mechanism of porous structure on the deformation failure of cement sheaths under hydraulic pressure is still unclear. To solve this problem, a net slurry cement sheath and a liquid silicon cement sheath were prepared by using a cement material and a liquid silicon suspension. The distributions of the pore radius and spatial location were analyzed using computed tomography scanning and statistics to obtain their probability density distribution functions. Based on the distribution functions, the single-layer and double-layer porous reconstruction models of the net slurry cement sheath and liquid silicon cement sheath were constructed using a FLAC 3D program. A series of numerical simulations were conducted to study the deformation failure of the cement sheaths under in situ stress and hydraulic pressure. The effects of the porous and double-layer structures on the breakdown pressure, plastic failure zone, radial deformation, and stress distribution of the cement sheaths were analyzed. As a result, the mechanisms for the influence of the porous and double-layer structures on the failure mode, failure path, and interaction between the cement sheath and metal casing were revealed. The results of this research provide a theoretical basis for an in-depth understanding of the failure mechanisms of porous cement sheaths.
Detecting and characterizing special nuclear material for nuclear nonproliferation applications
Authors: Pozzi S. A. , He Z. , Hutchinson J. , Jovanovic I. , Lopez R. , Ogren K. , Nattress J. , Shy D. , Clarke S. D. 
Published: June 2023

AbstractThere is an urgent need for new, better instrumentation and techniques for detecting and characterizing special nuclear material (SNM), i.e., highly enriched uranium and plutonium. The development of improved instruments and techniques requires experiments performed with the SNM itself, which is of limited availability. This paper describes the findings of experiments performed at the National Criticality Experiments Research Center conducted using new instruments and techniques on unclassified, kg-quantity SNM objects. These experiments, performed in the framework of the Department of Energy, National Nuclear Security Administration Consortium for Monitoring, Technology, and Verification, focused on detecting, characterizing, and localizing SNM samples with masses ranging from 3.3 to 13.8 kg, including plutonium and highly enriched uranium using prototype detectors and techniques. The work demonstrates SNM detection and characterization using recently-developed prototype detection systems. Specifically, we present new results in passive detection and imaging of plutonium and uranium objects using gamma-ray and dual particle (fast neutron and gamma-ray) imaging. We also present a new analysis of the delayed neutron emissions during active interrogation of uranium using a neutron generator.
Drosophila mutants lacking the glial neurotransmitter-modifying enzyme Ebony exhibit low neurotransmitter levels and altered behavior
Authors: Pantalia Meghan , Lin Zhi , Tener Samantha J. , Qiao Bing , Tang Grace , Ulgherait Matthew , O’Connor Reed , Delventhal Rebecca , Volpi Julia , Syed Sheyum , Itzhak Nissim , Canman Julie C. , Fernández María Paz , Shirasu-Hiza Mimi 
Published: June 2023

AbstractInhibitors of enzymes that inactivate amine neurotransmitters (dopamine, serotonin), such as catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), are thought to increase neurotransmitter levels and are widely used to treat Parkinson's disease and psychiatric disorders, yet the role of these enzymes in regulating behavior remains unclear. Here, we investigated the genetic loss of a similar enzyme in the model organism Drosophila melanogaster. Because the enzyme Ebony modifies and inactivates amine neurotransmitters, its loss is assumed to increase neurotransmitter levels, increasing behaviors such as aggression and courtship and decreasing sleep. Indeed, ebony mutants have been described since 1960 as "aggressive mutants," though this behavior has not been quantified. Using automated machine learning-based analyses, we quantitatively confirmed that ebony mutants exhibited increased aggressive behaviors such as boxing but also decreased courtship behaviors and increased sleep. Through tissue-specific knockdown, we found that ebony’s role in these behaviors was specific to glia. Unexpectedly, direct measurement of amine neurotransmitters in ebony brains revealed that their levels were not increased but reduced. Thus, increased aggression is the anomalous behavior for this neurotransmitter profile. We further found that ebony mutants exhibited increased aggression only when fighting each other, not when fighting wild-type controls. Moreover, fights between ebony mutants were less likely to end with a clear winner than fights between controls or fights between ebony mutants and controls. In ebony vs. control fights, ebony mutants were more likely to win. Together, these results suggest that ebony mutants exhibit prolonged aggressive behavior only in a specific context, with an equally dominant opponent.
Bedaquiline- and clofazimine- selected Mycobacterium tuberculosis mutants: further insights on resistance driven largely by Rv0678
Authors: Snobre J. , Villellas M. C. , Coeck N. , Mulders W. , Tzfadia O. , de Jong B. C. , Andries K. , Rigouts L. 
Published: June 2023

AbstractDrug-resistant tuberculosis is a serious global health threat. Bedaquiline (BDQ) is a relatively new core drug, targeting the respiratory chain inMycobacterium tuberculosis(Mtb). While mutations in the BDQ target gene,atpE,are rare in clinical isolates, mutations in theRv0678gene, a transcriptional repressor regulating the efflux pump MmpS5-MmpL5,are increasingly observed, and have been linked to worse treatment outcomes. Nevertheless, underlying mechanisms of (cross)-resistance remain incompletely resolved. Our study aims to distinguish resistance associated variants from other polymorphisms, by assessing the in vitro onset of mutations under drug pressure, combined with their impact on minimum inhibitory concentrations (MICs) and on protein stability. For this purpose, isolates were exposed in vitro to sub-lethal concentrations of BDQ or clofazimine (CFZ). Selected colonies had BDQ- and CFZ-MICs determined on 7H10 and 7H11 agar. Sanger sequencing and additional Deeplex Myc-TB and whole genome sequencing (WGS) for a subset of isolates were used to search for mutations inRv0678, atpEandpepQ. In silico characterization of relevant mutations was performed using computational tools. We found that colonies that grew on BDQ medium had mutations inRv0678,atpEorpepQ, while CFZ-exposed isolates presented mutations inRv0678andpepQ, but none inatpE. Twenty-eightRv0678mutations had previously been described among in vitro selected mutants or in patients’ isolates, while 85 were new. Mutations were scattered across theRv0678gene without apparent hotspot. While mostRv0678mutations led to an increased BDQ- and/or CFZ-MIC, only a part of them surpassed the critical concentration (69.1% for BDQ and 87.9% for CFZ). Among the mutations leading to elevated MICs for BDQ and CFZ, we report a synonymous Val1Val mutation in theRv0678start codon. Finally,in silico characterization ofRv0678mutations suggests that especially the C46R mutant may renderRv0678less stable.
Comparing mechanism-based and machine learning models for predicting the effects of glucose accessibility on tumor cell proliferation
Authors: Yang Jianchen , Virostko Jack , Liu Junyan , Jarrett Angela M. , Hormuth David A. , Yankeelov Thomas E. 
Published: June 2023

AbstractGlucose plays a central role in tumor metabolism and development and is a target for novel therapeutics. To characterize the response of cancer cells to blockade of glucose uptake, we collected time-resolved microscopy data to track the growth of MDA-MB-231 breast cancer cells. We then developed a mechanism-based, mathematical model to predict how a glucose transporter (GLUT1) inhibitor (Cytochalasin B) influences the growth of the MDA-MB-231 cells by limiting access to glucose. The model includes a parameter describing dose dependent inhibition to quantify both the total glucose level in the system and the glucose level accessible to the tumor cells. Four common machine learning models were also used to predict tumor cell growth. Both the mechanism-based and machine learning models were trained and validated, and the prediction error was evaluated by the coefficient of determination (R2). The random forest model provided the highest accuracy predicting cell dynamics (R2 = 0.92), followed by the decision tree (R2 = 0.89),k-nearest-neighbor regression (R2 = 0.84), mechanism-based (R2 = 0.77), and linear regression model (R2 = 0.69). Thus, the mechanism-based model has a predictive capability comparable to machine learning models with the added benefit of elucidating biological mechanisms.
Balance-energy of resting state network in obsessive-compulsive disorder
Authors: Talesh Alireza , Zarei Asghar , Yazdi-Ravandi Saeid , Ghaleiha Ali , Shamsaei Farshid , Matinnia Nasrin , Shams Jamal , Ahmadpanah Mohammad , Taslimi Zahra , Moghimbeigi Abbas , Khosrowabadi Reza 
Published: June 2023

AbstractStability of the brain functional network is directly linked to organization of synchronous and anti-synchronous activities. Nevertheless, impact of arrangement of positive and negative links called links topology requires to be well understood. In this study, we investigated how topology of the functional links reduce balance-energy of the brain network in obsessive-compulsive disorder (OCD) and push the network to a more stable state as compared to healthy controls. Therefore, functional associations between the regions were measured using the phase synchrony between the EEG activities. Subsequently, balance-energy of the brain functional network was estimated based on the quality of triadic interactions. Occurrence rates of four different types of triadic interactions including weak and strong balanced, and unbalanced interactions were compared. In addition, impact of the links topology was also investigated by looking at the tendency of positive and negative links to making hubs. Our results showed although the number of positive and negative links were not statistically different between OCD and healthy controls, but positive links in OCDs’ brain networks have more tendency to make hub. Moreover, lower number of unbalanced triads and higher number of strongly balanced triad reduced the balance-energy in OCDs’ brain networks that conceptually has less requirement to change. We hope these findings could shed a light on better understanding of brain functional network in OCD.
Machine learning-based somatic variant calling in cell-free DNA of metastatic breast cancer patients using large NGS panels
Authors: Jongbloed Elisabeth M. , Jansen Maurice P. H. M. , de Weerd Vanja , Helmijr Jean A. , Beaufort Corine M. , Reinders Marcel J. T. , van Marion Ronald , van IJcken Wilfred F. J. , Sonke Gabe S. , Konings Inge R. , Jager Agnes , Martens John W. M. , Wilting Saskia M. , Makrodimitris Stavros 
Published: June 2023

AbstractNext generation sequencing of cell-free DNA (cfDNA) is a promising method for treatment monitoring and therapy selection in metastatic breast cancer (MBC). However, distinguishing tumor-specific variants from sequencing artefacts and germline variation with low false discovery rate is challenging when using large targeted sequencing panels covering many tumor suppressor genes. To address this, we built a machine learning model to remove false positive variant calls and augmented it with additional filters to ensure selection of tumor-derived variants. We used cfDNA of 70 MBC patients profiled with both the small targeted Oncomine breast panel (Thermofisher) and the much larger Qiaseq Human Breast Cancer Panel (Qiagen). The model was trained on the panels’ common regions using Oncomine hotspot mutations as ground truth. Applied to Qiaseq data, it achieved 35% sensitivity and 36% precision, outperforming basic filtering. For 20 patients we used germline DNA to filter for somatic variants and obtained 245 variants in total, while our model found seven variants, of which six were also detected using the germline strategy. In ten tumor-free individuals, our method detected in total one (potentially germline) variant, in contrast to 521 variants detected without our model. These results indicate that our model largely detects somatic variants.
The distinction between irritability and anger and their associations with impulsivity and subjective wellbeing
Authors: Gröndal Maria , Ask Karl , Winblad Stefan 
Published: June 2023

AbstractIrritability, anger, and impulsivity have important associations with psychological well-being. However, studying the internal relationships between such emotional constructs is challenging, largely because of the lack of precise operational definitions and extensively validated measurement tools. The aim of this study was to examine relationships between the above emotional constructs and how they relate to satisfaction with life and perceived negative impact on different life domains. Participants (N = 471) completed a self-report questionnaire online. Correlational analyses showed that higher levels of irritability and trait anger were associated with lower life satisfaction. Impulsivity displayed complex relationships with life satisfaction, with some aspects (sensation seeking) showing a positive relationship and others (urgency, lack of perseverance) showing a negative relationship. A two-factor Confirmatory Factor Analysis treating irritability and anger as separate constructs showed a better fit compared with a one-factor model, indicating that irritability and anger should be treated as separate constructs. An exploratory moderation analysis showed that higher irritability predicted increased anger only for participants scoring average to high on urgency (a facet of impulsivity). Our findings increase the understanding of the relationship between these dispositional constructs and supports the conceptualization of irritability and anger as related but distinct constructs.
Multiple factors contribute to flight behaviors during fear conditioning
Authors: Furuyama Takafumi , Imayoshi Ayana , Iyobe Toyo , Ono Munenori , Ishikawa Tatsuya , Ozaki Noriyuki , Kato Nobuo , Yamamoto Ryo 
Published: June 2023

AbstractShifting defensive mode from one to another by the imminence of threat is crucial for survival. The transition of defensive mode from freezing to flight is observed during the modified fear conditioning, however, the flight during fear conditioning is not well characterized. To characterize the flight behaviors during the fear conditioning, we conducted experiments in male mice focusing on the influence of the context, the intensity of the unconditioned stimulus and conditioned stimulus (CS), the schedule of conditioning, and the state of the subject. Flight behaviors triggered by salient CS showed characteristics of fear-potentiated defensive behaviors depending on the conditioned context, while repetitive conditioning enhanced the expression of the flight and developed an association between the CS and the flight. The salient auditory stimulus was the primary factor to trigger flight behaviors. Also, the spaced conditioning increased the expression of flight behaviors. Taken together, the flight behavior during fear conditioning is not a simple conditioned response nor simple fear-potentiated behavior, but a complicated mixture of multiple components of defensive behaviors. The transition of defensive mode could be induced by the integration of multiple innate and learned components of fear or anxiety.
Significant contributions of trimethylamine to sulfuric acid nucleation in polluted environments
Authors: Cai Runlong , Yin Rujing , Li Xue , Xie Hong-Bin , Yang Dongsen , Kerminen Veli-Matti , Smith James N. , Ma Yan , Hao Jiming , Chen Jingwen , Kulmala Markku , Zheng Jun , Jiang Jingkun , Elm Jonas 
Published: June 2023

AbstractAs one of the least understood aerosol processes, nucleation can be a dominant source of atmospheric aerosols. Sulfuric acid (SA)-amine binary nucleation with dimethylamine (DMA) has been recognized as a governing mechanism in the polluted continental boundary layer. Here we demonstrate the importance of trimethylamine (TMA) for nucleation in the complex atmosphere and propose a molecular-level SA-DMA-TMA ternary nucleation mechanism as an improvement upon the conventional binary mechanism. Using the proposed mechanism, we could connect the gaseous amines to the SA-amine cluster signals measured in the atmosphere of urban Beijing. Results show that TMA can accelerate the SA-DMA-based new particle formation in Beijing by 50–100%. Considering the global abundance of TMA and DMA, our findings imply comparable importance of TMA and DMA to nucleation in the polluted continental boundary layer, with probably higher contributions from TMA in polluted rural environments and future urban environments with controlled DMA emissions.
MXene functionalized collagen biomaterials for cardiac tissue engineering driving iPSC-derived cardiomyocyte maturation
Authors: Asaro Giuseppe A. , Solazzo Matteo , Suku Meenakshi , Spurling Dahnan , Genoud Katelyn , Gonzalez Javier Gutierrez , Brien Fergal J. O’ , Nicolosi Valeria , Monaghan Michael G. 
Published: June 2023

AbstractElectroconductive biomaterials are gaining significant consideration for regeneration in tissues where electrical functionality is of crucial importance, such as myocardium, neural, musculoskeletal, and bone tissue. In this work, conductive biohybrid platforms were engineered by blending collagen type I and 2D MXene (Ti3C2Tx) and afterwards covalently crosslinking; to harness the biofunctionality of the protein component and the increased stiffness and enhanced electrical conductivity (matching and even surpassing native tissues) that two-dimensional titanium carbide provides. These MXene platforms were highly biocompatible and resulted in increased proliferation and cell spreading when seeded with fibroblasts. Conversely, they limited bacterial attachment (Staphylococcus aureus) and proliferation. When neonatal rat cardiomyocytes (nrCMs) were cultured on the substrates increased spreading and viability up to day 7 were studied when compared to control collagen substrates. Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were seeded and stimulated using electric-field generation in a custom-made bioreactor. The combination of an electroconductive substrate with an external electrical field enhanced cell growth, and significantly increased cx43 expression. This in vitro study convincingly demonstrates the potential of this engineered conductive biohybrid platform for cardiac tissue regeneration.