bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single-cell atlas of pig gastrulation as a resource for comparative embryology
Authors: Simpson Luke , Strange Andrew , Klisch Doris , Kraunsoe Sophie , Azami Takuya , Goszczynski Daniel , Le Minh Triet , Planells Benjamin , Holmes Nadine , Sang Fei , Henson Sonal , Loose Matthew , Nichols Jennifer , Alberio Ramiro 
Published: June 2024

AbstractCell-fate decisions during mammalian gastrulation are poorly understood outside of rodent embryos. The embryonic disc of pig embryos mirrors humans, making them a useful proxy for studying gastrulation. Here we present a single-cell transcriptomic atlas of pig gastrulation, revealing cell-fate emergence dynamics, as well as conserved and divergent gene programs governing early porcine, primate, and murine development. We highlight heterochronicity in extraembryonic cell-types, despite the broad conservation of cell-type-specific transcriptional programs. We apply these findings in combination with functional investigations, to outline conserved spatial, molecular, and temporal events during definitive endoderm specification. We find early FOXA2 + /TBXT- embryonic disc cells directly form definitive endoderm, contrasting later-emerging FOXA2/TBXT+ node/notochord progenitors. Unlike mesoderm, none of these progenitors undergo epithelial-to-mesenchymal transition. Endoderm/Node fate hinges on balanced WNT and hypoblast-derived NODAL, which is extinguished upon endodermal differentiation. These findings emphasise the interplay between temporal and topological signalling in fate determination during gastrulation.
Genetic influences on brain and cognitive health and their interactions with cardiovascular conditions and depression
Authors: Zhukovsky Peter , Tio Earvin S. , Coughlan Gillian , Bennett David A. , Wang Yanling , Hohman Timothy J. , Pizzagalli Diego A. , Mulsant Benoit H. , Voineskos Aristotle N. , Felsky Daniel 
Published: June 2024

AbstractApproximately 40% of dementia cases could be prevented or delayed by modifiable risk factors related to lifestyle and environment. These risk factors, such as depression and vascular disease, do not affect all individuals in the same way, likely due to inter-individual differences in genetics. However, the precise nature of how genetic risk profiles interact with modifiable risk factors to affect brain health is poorly understood. Here we combine multiple data resources, including genotyping and postmortem gene expression, to map the genetic landscape of brain structure and identify 367 loci associated with cortical thickness and 13 loci associated with white matter hyperintensities (P < 5×10−8), with several loci also showing a significant association with cognitive function. We show that among 220 unique genetic loci associated with cortical thickness in our genome-wide association studies (GWAS), 95 also showed evidence of interaction with depression or cardiovascular conditions. Polygenic risk scores based on our GWAS of inferior frontal thickness also interacted with hypertension in predicting executive function in the Canadian Longitudinal Study on Aging. These findings advance our understanding of the genetic underpinning of brain structure and show that genetic risk for brain and cognitive health is in part moderated by treatable mid-life factors.
Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1
Authors: Dans Madeline G. , Boulet Coralie , Watson Gabrielle M. , Nguyen William , Dziekan Jerzy M. , Evelyn Cindy , Reaksudsan Kitsanapong , Mehra Somya , Razook Zahra , Geoghegan Niall D. , Mlodzianoski Michael J. , Goodman Christopher Dean , Ling Dawson B. , Jonsdottir Thorey K. , Tong Joshua , Famodimu Mufuliat Toyin , Kristan Mojca , Pollard Harry , Stewart Lindsay B. , Brandner-Garrod Luke , Sutherland Colin J. , Delves Michael J. , McFadden Geoffrey I. , Barry Alyssa E. , Crabb Brendan S. , de Koning-Ward Tania F. , Rogers Kelly L. , Cowman Alan F. , Tham Wai-Hong , Sleebs Brad E. , Gilson Paul R. 
Published: June 2024

AbstractWith resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite’s lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.
Chemogenomics for NR1 nuclear hormone receptors
Authors: Isigkeit Laura , Schallmayer Espen , Busch Romy , Brunello Lorene , Menge Amelie , Elson Lewis , Müller Susanne , Knapp Stefan , Stolz Alexandra , Marschner Julian A. , Merk Daniel 
Published: June 2024

AbstractNuclear receptors (NRs) regulate transcription in response to ligand binding and NR modulation allows pharmacological control of gene expression. Although some NRs are relevant as drug targets, the NR1 family, which comprises 19 NRs binding to hormones, vitamins, and lipid metabolites, has only been partially explored from a translational perspective. To enable systematic target identification and validation for this protein family in phenotypic settings, we present an NR1 chemogenomic (CG) compound set optimized for complementary activity/selectivity profiles and chemical diversity. Based on broad profiling of candidates for specificity, toxicity, and off-target liabilities, sixty-nine comprehensively annotated NR1 agonists, antagonists and inverse agonists covering all members of the NR1 family and meeting potency and selectivity standards are included in the final NR1 CG set. Proof-of-concept application of this set reveals effects of NR1 members in autophagy, neuroinflammation and cancer cell death, and confirms the suitability of the set for target identification and validation.
Ecological drivers of ultraviolet colour evolution in snakes
Authors: Crowell Hayley L. , Curlis John David , Weller Hannah I. , Davis Rabosky Alison R. 
Published: June 2024

AbstractUltraviolet (UV) colour patterns invisible to humans are widespread in nature. However, research bias favouring species with conspicuous colours under sexual selection can limit our assessment of other ecological drivers of UV colour, like interactions between predators and prey. Here we demonstrate widespread UV colouration across Western Hemisphere snakes and find stronger support for a predator defence function than for reproduction. We find that UV colouration has evolved repeatedly in species with ecologies most sensitive to bird predation, with no sexual dichromatism at any life stage. By modelling visual systems of potential predators, we find that snake conspicuousness correlates with UV colouration and predator cone number, providing a plausible mechanism for selection. Our results suggest that UV reflectance should not be assumed absent in “cryptically coloured” animals, as signalling beyond human visual capacities may be a key outcome of species interactions in many taxa for which UV colour is likely underreported.
Disruption of myelin structure and oligodendrocyte maturation in a macaque model of congenital Zika infection
Authors: Tisoncik-Go Jennifer , Stokes Caleb , Whitmore Leanne S. , Newhouse Daniel J. , Voss Kathleen , Gustin Andrew , Sung Cheng-Jung , Smith Elise , Stencel-Baerenwald Jennifer , Parker Edward , Snyder Jessica M. , Shaw Dennis W. , Rajagopal Lakshmi , Kapur Raj P. , Adams Waldorf Kristina M. , Gale Michael 
Published: June 2024

AbstractZika virus (ZikV) infection during pregnancy can cause congenital Zika syndrome (CZS) and neurodevelopmental delay in infants, of which the pathogenesis remains poorly understood. We utilize an established female pigtail macaque maternal-to-fetal ZikV infection/exposure model to study fetal brain pathophysiology of CZS manifesting from ZikV exposure in utero. We find prenatal ZikV exposure leads to profound disruption of fetal myelin, with extensive downregulation in gene expression for key components of oligodendrocyte maturation and myelin production. Immunohistochemical analyses reveal marked decreases in myelin basic protein intensity and myelinated fiber density in ZikV-exposed animals. At the ultrastructural level, the myelin sheath in ZikV-exposed animals shows multi-focal decompaction, occurring concomitant with dysregulation of oligodendrocyte gene expression and maturation. These findings define fetal neuropathological profiles of ZikV-linked brain injury underlying CZS resulting from ZikV exposure in utero. Because myelin is critical for cortical development, ZikV-related perturbations in oligodendrocyte function may have long-term consequences on childhood neurodevelopment, even in the absence of overt microcephaly.
Intracranial EEG signals disentangle multi-areal neural dynamics of vicarious pain perception
Authors: Tan Huixin , Zeng Xiaoyu , Ni Jun , Liang Kun , Xu Cuiping , Zhang Yanyang , Wang Jiaxin , Li Zizhou , Yang Jiaxin , Han Chunlei , Gao Yuan , Yu Xinguang , Han Shihui , Meng Fangang , Ma Yina 
Published: June 2024

AbstractEmpathy enables understanding and sharing of others’ feelings. Human neuroimaging studies have identified critical brain regions supporting empathy for pain, including the anterior insula (AI), anterior cingulate (ACC), amygdala, and inferior frontal gyrus (IFG). However, to date, the precise spatio-temporal profiles of empathic neural responses and inter-regional communications remain elusive. Here, using intracranial electroencephalography, we investigated electrophysiological signatures of vicarious pain perception. Others’ pain perception induced early increases in high-gamma activity in IFG, beta power increases in ACC, but decreased beta power in AI and amygdala. Vicarious pain perception also altered the beta-band-coordinated coupling between ACC, AI, and amygdala, as well as increased modulation of IFG high-gamma amplitudes by beta phases of amygdala/AI/ACC. We identified a necessary combination of neural features for decoding vicarious pain perception. These spatio-temporally specific regional activities and inter-regional interactions within the empathy network suggest a neurodynamic model of human pain empathy.
Acetylation-dependent regulation of core spliceosome modulates hepatocellular carcinoma cassette exons and sensitivity to PARP inhibitors
Authors: Sun Linmao , Liu Yufeng , Guo Xinyu , Cui Tianming , Wu Chenghui , Tao Jie , Cheng Cheng , Chu Qi , Ji Changyong , Li Xianying , Guo Hongrui , Liang Shuhang , Zhou Huanran , Zhou Shuo , Ma Kun , Zhang Ning , Wang Jiabei , Liu Yao , Liu Lianxin 
Published: June 2024

AbstractDespite the importance of spliceosome core components in cellular processes, their roles in cancer development, including hepatocellular carcinoma (HCC), remain poorly understood. In this study, we uncover a critical role for SmD2, a core component of the spliceosome machinery, in modulating DNA damage in HCC through its impact on BRCA1/FANC cassette exons and expression. Our findings reveal that SmD2 depletion sensitizes HCC cells to PARP inhibitors, expanding the potential therapeutic targets. We also demonstrate that SmD2 acetylation by p300 leads to its degradation, while HDAC2-mediated deacetylation stabilizes SmD2. Importantly, we show that the combination of Romidepsin and Olaparib exhibits significant therapeutic potential in multiple HCC models, highlighting the promise of targeting SmD2 acetylation and HDAC2 inhibition alongside PARP inhibitors for HCC treatment.
Protective roles of thrombomodulin in cisplatin-induced nephrotoxicity through the inhibition of oxidative and endoplasmic reticulum stress
Authors: Yamamoto Hiroki , Ishida Yuko , Zhang Siying , Osako Miyu , Nosaka Mizuho , Kuninaka Yumi , Ishigami Akiko , Iwahashi Yuya , Aragane Miki , Matsumoto Lennon , Kimura Akihiko , Kondo Toshikazu 
Published: June 2024

AbstractCisplatin is an effective chemotherapeutic agent widely used for the treatment of various solid tumors. However, cisplatin has an important limitation in its use; currently, there is no method to ameliorate cisplatin-induced acute kidney injury (AKI). Thrombomodulin (TM) is well known not only for its role as a cofactor in the clinically important natural anticoagulation pathway but also for its anti-inflammatory properties. Here, we investigated the effects of TM in cisplatin-induced AKI. In mice intraperitoneally injected with 15 mg/kg cisplatin, TM (10 mg/kg) or PBS was administered intravenously at 24 h after cisplatin injection. TM significantly attenuated cisplatin-induced nephrotoxicity with the suppressed elevation of blood urea nitrogen and serum creatinine, and reduced histological damages. Actually, TM treatment significantly alleviated oxidative stress-induced apoptosis by reducing reactive oxygen species (ROS) levels in cisplatin-treated renal proximal tubular epithelial cells (RPTECs) in vitro. Furthermore, TM clarified cisplatin-induced apoptosis by reducing caspase-3 levels. In addition, TM attenuated the endoplasmic reticulum (ER) stress signaling pathway in both renal tissues and RPTECs to protect the kidneys from cisplatin-induced AKI. These findings suggest that TM is a potential protectant against cisplatin-induced nephrotoxicity through suppressing ROS generation and ER stress in response to cisplatin.
Stability evaluation of open-pit mine slope based on Bayesian optimization 1D-CNN
Authors: Lyu Jinguo , Hu Taihong , Liu Guangwei , Cao Bo , Wang Wenqi , Li Shixu 
Published: June 2024

AbstractAs mechanized open-pit coal mining intensifies, assessing and predicting slope stability has become increasingly important. To address the limitations of traditional mechanical calculations, numerical simulations, and physical experiments, this paper identifies the key factors impacting slope stability in open-pit mines and develops a multi-parameter sample data set. The study employs hyperparameters optimized using a Bayesian algorithm, introduces additional convolutional layers, and combines the Adam optimizer with dropout techniques to enhance the feature extraction and performance of one-dimensional convolutional neural networks (1D-CNN). This leads to a Bayesian-optimized one-dimensional convolutional neural network (B-1D MCNN) model for predicting slope stability.The study evaluates the classification performance and accuracy of various models for slope stability, including BP neural networks, genetic algorithm-optimized convolutional neural networks, 1D-CNN, and B-1D MCNN, using accuracy, precision, and F1-score as metrics. The analysis also examines the influence of factor indicators and training set length on the model's output to assess its generalization capabilities.The research findings suggest that: (1) the B-1D MCNN model for evaluating slope stability demonstrates the capability to accurately depict the nonlinear correlation between influencing factors and slope stability. (2) Compared with other models, the B-1D MCNN model has shown enhancements of 10.96% to 27.85%, 10.26% to 28.55%, and 8.98% to 25.05% in terms of Accuracy, F1-Score, and Precision, respectively. (3) As the length of the training dataset increases, the performance of the model improves accordingly. (4) The B-1D MCNN model shows a generalization power of 87.5%.
Numerical simulation research on thermal insulation performance of composite heat-insulation zone structure in hydrothermal high-temperature mine
Authors: Li Yanhe , Wan Zhijun , Yu Zhenzi , Shi Peng , Zhang Bo , Zhang Yuan 
Published: June 2024

AbstractIn hydrothermal high-temperature abnormal mines, the composite heat-insulation zone structure, formed through a combination of guniting and grouting, serves to mitigate heat dissipation from the surrounding rock into the airflow. To comprehensively understand the thermal insulation performance of the composite heat-insulation zone structure, this study employs numerical simulation to analyze the following aspects: the variation in the temperature field within the surrounding rock of the roadway without insulation, the influence of structural parameters of the composite heat-insulation zone on temperature distribution in the surrounding rock of the roadway, and the thermal insulation effectiveness of the composite heat-insulation zone with varying structures. The findings indicate that the temperature distribution within the surrounding rock of the roadway lacking a heat-insulation zone is relatively uniform. However, as ventilation time extends, the heat regulation zone within the surrounding rock gradually extends deeper, ultimately forming an elliptical cooling area. The composite heat-insulation zone structure effectively mitigates heat transfer from deeper surrounding rock to the roadway wall, consequently altering the scope of the roadway's heat regulation zone. Enhancing the thermal insulation performance of the composite heat-insulation zone structure can be achieved by increasing the thickness of the thermal insulation layer, adjusting grouting rate and depth, and reducing the thermal conductivity of insulation materials. The thermal insulation effectiveness of the thermal insulation layer surpasses that of the grouting layer, with its performance primarily influenced by the thermal conductivity of the materials used. Simulation results demonstrate that the composite heat-insulation zone structure reduces the maximum heat flux on the roadway wall from 47.4 to 37.7 W/m2, resulting in a 20% reduction in heat transfer from deeper surrounding rock. These findings offer valuable insights for implementing thermal insulation techniques in hydrothermal high-temperature anomaly mines.
Unveiling green corrosion inhibitor of Aloe vera extracts for API 5L steel in seawater environment
Authors: Royani Ahmad , Hanafi Muhammad , Mubarak Nabisab Mujawar , Priyotomo Gadang , Aigbodion Victor Sunday , Musabikha Siti , Manaf Azwar 
Published: June 2024

AbstractThis study evaluated Aloe vera extract as a green inhibitor to prevent corrosion in seawater environments. A. vera extract was produced by maceration with methanol﻿–water at room temperature. Electrochemical techniques were used to evaluate the corrosion inhibitor effectiveness of the A. vera extract. The morphology of the corrosion products was analyzed by FE-SEM equipped with EDS and AFM. FT-IR and LCMS characterized the functional and structural groups in this extract. The electrochemical measurements show that A. vera extract could effectively reduce the corrosion of API 5L steel in seawater environments. Inhibition efficiency (IE) increases with increasing concentration. Optimal corrosion inhibition efficiency of around 83.75% (PDP) and 88.60% (EIS) was obtained by adding 300 mg L−1 of extract at 310 K. Furthermore, the higher the concentration of A. vera extract, the greater the activation energy (Ea), with the highest activation energy being 48.24 kJ mol−1 for the concentration of 300 mg L−1. Conversely, increasing the temperature and exposure duration reduces the corrosion inhibition efficiency (IE) values; the best exposure period was 30 min with 88.34% IE by a concentration of 300 mg L−1 at 300 K. This corrosion inhibition is achieved by the adsorption process of A. vera bioactive on metal surfaces with a mixed inhibitor through a physisorption-chemisorption mechanism. This finding was confirmed by the smoother surface morphology of the steel treated with A. vera extract than without. This unveiling investigation found that A. vera extract has the potential to be an environmentally friendly corrosion inhibitor in the seawater environment.
Rapid photocatalytic dye degradation, enhanced antibacterial and antifungal activities of silver stacked zinc oxide garnished on carbon nanotubes
Authors: Wagh Snehal S. , Chougale Akanksha S. , Survase Avinash A. , Patil Rajendra S. , Naik Nithesh , Naushad Mu. , Pathan Habib M. 
Published: June 2024

AbstractA composite of Zinc oxide loaded with 5-weight % silver decorated on carbon nanotubes (Ag-loaded ZnO: CNT) was synthesized using a simple refluxed chemical method. The influence of deviation in the weight % of carbon nanotube loading on photocatalytic dye degradation (methylene blue and rose bengal) and antibiotic (antimicrobial and antifungal) performance was investigated in this study. The light capture ability of Ag-loaded ZnO:CNT in the visible region was higher in photocatalytic activity than that of Ag-loaded ZnO and ZnO:CNT. The bandgap of the Ag-loaded ZnO: CNT was tuned owing to the surface plasmon resonance effect. The photocatalytic degradation investigations were optimized by varying the wt% in CNTs, pH of dye solution, concentration of the dye solution, and amount of catalytic dose. Around 100% photocatalytic efficiency in 2 min against MB dye was observed for Ag doped ZnO with 10 wt% CNT composite at pH 9, at a rate constant 1.48 min−1. Bipolaris sorokiniana fungus was first time tested against a composite material, which demonstrated optimum fungal inhibition efficiency of 48%. They were also tested against the bacterial strains Staphylococcus aureus, Bacillus cerius, Proteus vulgaris, and Salmonella typhimurium, which showed promising antibacterial activity compared to commercially available drugs. The composite of Ag doped ZnO with 5 wt% CNT has shown competitive zone inhibition efficacy of 21.66 ± 0.57, 15.66 ± 0.57, 13.66 ± 0.57 against bacterial strains Bacillus cerius, Proteus vulgaris, and Salmonella typhimurium which were tested for the first time against Ag-loaded ZnO:CNT.
Identifying gut microbiota with high specificity for ischemic stroke with large vessel occlusion
Authors: He Ping , Jiang Chen , Ni Jianqiang , Zhang Xiaoxuan , Wu Zhifeng , Chen Gengjing , Huang Jin , Dai Zheng , Ji Wei , Li Lei , Chen Kefei , Shi Yachen 
Published: June 2024

AbstractGut microbiota can regulate the metabolic and immunological aspects of ischemic stroke and modulate the treatment effects. The present study aimed to identify specific changes in gut microbiota in patients with large vessel occlusion (LVO) ischemic stroke and assess the potential association between gut microbiota and clinical features of ischemic stroke. A total of 63 CSVD patients, 64 cerebral small vessel disease (CSVD) patients, and 36 matching normal controls (NCs) were included in this study. The fecal samples were collected for all participants and analyzed for gut microbiota using 16S rRNA gene sequencing technology. The abundances of five gut microbiota, including genera Bifidobacterium, Butyricimonas, Blautia, and Dorea and species Bifidobacterium_longum, showed significant changes with high specificity in the LVO patients as compared to the NCs and CSVD patients. In LVO patients, the genera Bifidobacterium and Blautia and species Bifidobacterium_longum were significantly correlated with the National Institutes of Health Stroke Scale (NIHSS) scores at the admission and discharge of the patients. Serum triglyceride levels could significantly affect the association of the abundance of genus Bifidobacterium and species Bifidobacterium_longum with the NIHSS scores at admission and modified Rankin Scale (mRS) at discharge in LVO patients. The identification of five gut microbiota with high specificity were identified in the early stage of LVO stroke, which contributed to performed an effective clinical management for LVO ischemic stroke.