bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harnessing the reverse cholesterol transport pathway to favor differentiation of monocyte-derived APCs and antitumor responses
Authors: Raccosta Laura , Marinozzi Maura , Costantini Susan , Maggioni Daniela , Ferreira Lorena Maria , Corna Gianfranca , Zordan Paola , Sorice Angela , Farinello Diego , Bianchessi Silvia , Riba Michela , Lazarevic Dejan , Provero Paolo , Mack Matthias , Bondanza Attilio , Nalvarte Ivan , Gustafsson J-A , Ranzani Valeria , De Sanctis Francesco , Ugel Stefano , Baron Silvère , Lobaccaro Jean-Marc A. , Pontini Lorenzo , Pacciarini Manuela , Traversari Catia , Pagani Massimiliano , Bronte Vincenzo , Sitia Giovanni , Antonson Per , Brendolan Andrea , Budillon Alfredo , Russo Vincenzo 
Published: February 2023

AbstractLipid and cholesterol metabolism play a crucial role in tumor cell behavior and in shaping the tumor microenvironment. In particular, enzymatic and non-enzymatic cholesterol metabolism, and derived metabolites control dendritic cell (DC) functions, ultimately impacting tumor antigen presentation within and outside the tumor mass, dampening tumor immunity and immunotherapeutic attempts. The mechanisms accounting for such events remain largely to be defined. Here we perturbed (oxy)sterol metabolism genetically and pharmacologically and analyzed the tumor lipidome landscape in relation to the tumor-infiltrating immune cells. We report that perturbing the lipidome of tumor microenvironment by the expression of sulfotransferase 2B1b crucial in cholesterol and oxysterol sulfate synthesis, favored intratumoral representation of monocyte-derived antigen-presenting cells, including monocyte-DCs. We also found that treating mice with a newly developed antagonist of the oxysterol receptors Liver X Receptors (LXRs), promoted intratumoral monocyte-DC differentiation, delayed tumor growth and synergized with anti-PD-1 immunotherapy and adoptive T cell therapy. Of note, looking at LXR/cholesterol gene signature in melanoma patients treated with anti-PD-1-based immunotherapy predicted diverse clinical outcomes. Indeed, patients whose tumors were poorly infiltrated by monocytes/macrophages expressing LXR target genes showed improved survival over the course of therapy. Thus, our data support a role for (oxy)sterol metabolism in shaping monocyte-to-DC differentiation, and in tumor antigen presentation critical for responsiveness to immunotherapy. The identification of a new LXR antagonist opens new treatment avenues for cancer patients.
Long noncoding RNA ENST00000436340 promotes podocyte injury in diabetic kidney disease by facilitating the association of PTBP1 with RAB3B
Authors: Hu Jinxiu , Wang Qimeng , Fan Xiaoting , Zhen Junhui , Wang Cheng , Chen Huimin , Liu Yingxiao , Zhou Ping , Zhang Tingwei , Huang Tongtong , Wang Rong , Lv Zhimei 
Published: February 2023

AbstractDysfunction of podocytes has been regarded as an important early pathologic characteristic of diabetic kidney disease (DKD), but the regulatory role of long noncoding RNAs (lncRNAs) in this process remains largely unknown. Here, we performed RNA sequencing in kidney tissues isolated from DKD patients and nondiabetic renal cancer patients undergoing surgical resection and discovered that the novel lncRNA ENST00000436340 was upregulated in DKD patients and high glucose-induced podocytes, and we showed a significant correlation between ENST00000436340 and kidney injury. Gain- and loss-of-function experiments showed that silencing ENST00000436340 alleviated high glucose-induced podocyte injury and cytoskeleton rearrangement. Mechanistically, we showed that fat mass and obesity- associate gene (FTO)-mediated m6A induced the upregulation of ENST00000436340. ENST00000436340 interacted with polypyrimidine tract binding protein 1 (PTBP1) and augmented PTBP1 binding to RAB3B mRNA, promoted RAB3B mRNA degradation, and thereby caused cytoskeleton rearrangement and inhibition of GLUT4 translocation to the plasma membrane, leading to podocyte injury and DKD progression. Together, our results suggested that upregulation of ENST00000436340 could promote podocyte injury through PTBP1-dependent RAB3B regulation, thus suggesting a novel form of lncRNA-mediated epigenetic regulation of podocytes that contributes to the pathogenesis of DKD.
Coadaptation fostered by the SLIT2-ROBO1 axis facilitates liver metastasis of pancreatic ductal adenocarcinoma
Authors: Li Qing , Zhang Xiao-Xin , Hu Li-Peng , Ni Bo , Li Dong-Xue , Wang Xu , Jiang Shu-Heng , Li Hui , Yang Min-Wei , Jiang Yong-Sheng , Xu Chun-Jie , Zhang Xue-Li , Zhang Yan-Li , Huang Pei-Qi , Yang Qin , Zhou Yang , Gu Jian-ren , Xiao Gary Gui-Shan , Sun Yong-wei , Li Jun , Zhang Zhi-Gang 
Published: February 2023

AbstractTo explore the mechanism of coadaptation and the potential drivers of pancreatic ductal adenocarcinoma (PDAC) metastasis to the liver, we study key molecules involved in this process and their translational value. Premetastatic niche (PMN) and macrometastatic niche (MMN) formation in a mouse model is observed via CT combined with 3D organ reconstruction bioluminescence imaging, and then we screen slit guidance ligand 2 (SLIT2) and its receptor roundabout guidance receptor 1 (ROBO1) as important factors. After we confirm the expression and distribution of SLIT2 and ROBO1 in samples from PDAC patients and several mouse models, we discover that SLIT2-ROBO1-mediated coadaptation facilitated the implantation and outgrowth of PDAC disseminated tumour cells (DTCs) in the liver. We also demonstrate the dependence receptor (DR) characteristics of ROBO1 in a follow-up mechanistic study. A neutralizing antibody targeting ROBO1 significantly attenuate liver metastasis of PDAC by preventing the coadaptation effect. Thus, we demonstrate that coadaptation is supported by the DR characteristics in the PMN and MMN.
Investigating microstructure evolution of lithium metal during plating and stripping via operando X-ray tomographic microscopy
Authors: Sadd Matthew , Xiong Shizhao , Bowen Jacob R. , Marone Federica , Matic Aleksandar 
Published: February 2023

AbstractEfficient lithium metal stripping and plating operation capable of maintaining electronic and ionic conductivity is crucial to develop safe lithium metal batteries. However, monitoring lithium metal microstructure evolution during cell cycling is challenging. Here, we report the development of an operando synchrotron X-ray tomographic microscopy method capable of probing in real-time the formation, growth, and dissolution of Li microstructures during the cycling of a Li||Cu cell containing a standard non-aqueous liquid electrolyte solution. The analyses of the operando X-ray tomographic microscopy measurements enable tracking the evolution of deposited Li metal as a function of time and applied current density and distinguishing the formation of electrochemically inactive Li from the active bulk of Li microstructures. Furthermore, in-depth analyses of the Li microstructures shed some light on the structural connectivity of deposited Li at different current densities as well as the formation mechanism of fast-growing fractal Li microstructures, which are ultimately responsible for cell failure.
A NPAS4–NuA4 complex couples synaptic activity to DNA repair
Authors: Pollina Elizabeth A. , Gilliam Daniel T. , Landau Andrew T. , Lin Cindy , Pajarillo Naomi , Davis Christopher P. , Harmin David A. , Yap Ee-Lynn , Vogel Ian R. , Griffith Eric C. , Nagy M. Aurel , Ling Emi , Duffy Erin E. , Sabatini Bernardo L. , Weitz Charles J. , Greenberg Michael E. 
Published: February 2023

AbstractNeuronal activity is crucial for adaptive circuit remodelling but poses an inherent risk to the stability of the genome across the long lifespan of postmitotic neurons1–5. Whether neurons have acquired specialized genome protection mechanisms that enable them to withstand decades of potentially damaging stimuli during periods of heightened activity is unknown. Here we identify an activity-dependent DNA repair mechanism in which a new form of the NuA4–TIP60 chromatin modifier assembles in activated neurons around the inducible, neuronal-specific transcription factor NPAS4. We purify this complex from the brain and demonstrate its functions in eliciting activity-dependent changes to neuronal transcriptomes and circuitry. By characterizing the landscape of activity-induced DNA double-strand breaks in the brain, we show that NPAS4–NuA4 binds to recurrently damaged regulatory elements and recruits additional DNA repair machinery to stimulate their repair. Gene regulatory elements bound by NPAS4–NuA4 are partially protected against age-dependent accumulation of somatic mutations. Impaired NPAS4–NuA4 signalling leads to a cascade of cellular defects, including dysregulated activity-dependent transcriptional responses, loss of control over neuronal inhibition and genome instability, which all culminate to reduce organismal lifespan. In addition, mutations in several components of the NuA4 complex are reported to lead to neurodevelopmental and autism spectrum disorders. Together, these findings identify a neuronal-specific complex that couples neuronal activity directly to genome preservation, the disruption of which may contribute to developmental disorders, neurodegeneration and ageing.
Effects of Al2O3, SiO2 nanoparticles, and g-c3n4 nanosheets on biocement production from agricultural wastes
Authors: Abdelsalam Essam M. , Samer Mohamed , Seifelnasr Amira , Moselhy Mohamed A. , Ibrahim Hatem H. A. , Faried Maryam , Attia Yasser A. 
Published: February 2023

AbstractEnvironmental issues are brought up concerning the production of Portland cement. As a result, biocement serves as a reliable substitute for Portland cement in green construction projects. This study created a brand-new technique to create high-quality biocement from agricultural wastes. The technique is based on nanomaterials that improve and accelerate the "Microbially Induced Calcite Precipitation (MICP)" process, which improves the quality of the biocement produced. The mixture was further mixed with the addition of 5 mg/l of graphitic carbon nitride nanosheets (g-C3N4 NSs), alumina nanoparticles (Al2O3 NPs), or silica nanoparticles (SiO2 NPs). The cement: sand ratio was 1:3, the ash: cement ratio was 1:9, and water: cement ratio was 1:2. Cubes molds were prepared, and then cast and compacted. Subsequent de-molding, all specimens were cured in nutrient broth-urea (NBU) media until testing at 28 days. The medium was replenished at an interval of 7 days. The results show that the addition of 5 mg/l of g-C3N4 NSs with corncob ash delivered the highest “Compressive Strength” and the highest “Flexural Strength” of biocement mortar cubes of 18 and 7.6 megapascal (MPa), respectively; and an acceptable “Water Absorption” (5.42%) compared to all other treatments. This treatment delivered a “Compressive Strength”, “Flexural Strength”, and “Water Absorption” reduction of 1.67, 1.26, and 1.21 times the control (standard Portland cement). It was concluded that adding 5 mg/l of g-C3N4 NSs to the cementitious mixture enhances its properties, where the resulting biocement is a promising substitute for conventional Portland cement. Adding nanomaterials to cement reduces its permeability to ions, increasing its strength and durability. The use of these nanomaterials can enhance the performance of concrete infrastructures. The use of nanoparticles is an effective solution to reduce the environmental impact associated with concrete production.
Generalisability of fetal ultrasound deep learning models to low-resource imaging settings in five African countries
Authors: Sendra-Balcells Carla , Campello Víctor M. , Torrents-Barrena Jordina , Ahmed Yahya Ali , Elattar Mustafa , Ohene-Botwe Benard , Nyangulu Pempho , Stones William , Ammar Mohammed , Benamer Lamya Nawal , Kisembo Harriet Nalubega , Sereke Senai Goitom , Wanyonyi Sikolia Z. , Temmerman Marleen , Gratacós Eduard , Bonet Elisenda , Eixarch Elisenda , Mikolaj Kamil , Tolsgaard Martin Grønnebæk , Lekadir Karim 
Published: February 2023

AbstractMost artificial intelligence (AI) research and innovations have concentrated in high-income countries, where imaging data, IT infrastructures and clinical expertise are plentiful. However, slower progress has been made in limited-resource environments where medical imaging is needed. For example, in Sub-Saharan Africa, the rate of perinatal mortality is very high due to limited access to antenatal screening. In these countries, AI models could be implemented to help clinicians acquire fetal ultrasound planes for the diagnosis of fetal abnormalities. So far, deep learning models have been proposed to identify standard fetal planes, but there is no evidence of their ability to generalise in centres with low resources, i.e. with limited access to high-end ultrasound equipment and ultrasound data. This work investigates for the first time different strategies to reduce the domain-shift effect arising from a fetal plane classification model trained on one clinical centre with high-resource settings and transferred to a new centre with low-resource settings. To that end, a classifier trained with 1792 patients from Spain is first evaluated on a new centre in Denmark in optimal conditions with 1008 patients and is later optimised to reach the same performance in five African centres (Egypt, Algeria, Uganda, Ghana and Malawi) with 25 patients each. The results show that a transfer learning approach for domain adaptation can be a solution to integrate small-size African samples with existing large-scale databases in developed countries. In particular, the model can be re-aligned and optimised to boost the performance on African populations by increasing the recall to $$0.92 \pm 0.04$$

0.92
±
0.04

and at the same time maintaining a high precision across centres. This framework shows promise for building new AI models generalisable across clinical centres with limited data acquired in challenging and heterogeneous conditions and calls for further research to develop new solutions for the usability of AI in countries with fewer resources and, consequently, in higher need of clinical support.
The choice of an autocorrelation length in dark-field lung imaging
Authors: Spindler Simon , Etter Dominik , Rawlik Michał , Polikarpov Maxim , Romano Lucia , Shi Zhitian , Jefimovs Konstantins , Wang Zhentian , Stampanoni Marco 
Published: February 2023

AbstractRespiratory diseases are one of the most common causes of death, and their early detection is crucial for prompt treatment. X-ray dark-field radiography (XDFR) is a promising tool to image objects with unresolved micro-structures such as lungs. Using Talbot-Lau XDFR, we imaged inflated porcine lungs together with Polymethylmethacrylat (PMMA) microspheres (in air) of diameter sizes between 20 and 500 $$\upmu \hbox {m}$$

μ
m

over an autocorrelation range of 0.8–5.2 $$\upmu \hbox {m}$$

μ
m

. The results indicate that the dark-field extinction coefficient of porcine lungs is similar to that of densely-packed PMMA spheres with diameter of $${200}\,\upmu \hbox {m}$$

200

μ
m

, which is approximately the mean alveolar structure size. We evaluated that, in our case, the autocorrelation length would have to be limited to $${0.57}\,\upmu \hbox {m}$$

0.57

μ
m

in order to image $${20}\,\hbox {cm}$$

20

cm

-thick lung tissue without critical visibility reduction (signal saturation). We identify the autocorrelation length to be the critical parameter of an interferometer that allows to avoid signal saturation in clinical lung dark-field imaging.
Multi-dimensional safety risk assessment on coal mines under the profitability dilemma
Authors: You Qi , Yao Qingguo , Song Ruixin , Yu Kai , Xu Cuicui , Cao Haiying 
Published: February 2023

AbstractChina is a major coal producer, with huge differences in coal production and safety situations between the South and the North. Taking province A as an example, its coal enterprises have low output, poor efficiency, backward equipment, and low-quality personnel. The output accounts for 0.08% of the country, and the number of deaths accounts for 2.2% of the country, the safety situation of coal enterprises in province A is severe. In order to study the safety risk situation of coal mines under difficult conditions, this paper screens 98 factor indexes including multiple subjects such as enterprise managers, front-line workers, government supervisors, external environment, work quality, stress factors, economic factors, and other dimensions. For different data, the indicator weights were calculated using triangular fuzzy number, entropy weight method, CRITIC method, and three rough set methods in a total of six methods. The comprehensive weights of the indicators were obtained using the proposed new comprehensive weight method. The current situation of safety work of four coal mining enterprises and three levels of government supervision departments was evaluated, and the evaluation results were compared with other existing data to verify the reliability of the evaluation system. The horizontal comparison of the evaluation results indicates the main problems of each subject; the longitudinal comparison points out the problems that need to be solved with the assistance of higher-level enterprises and the central government, and corresponding suggestions for coal mining enterprises and government departments are put forward to reduce the safety risks of troubled coal mining enterprises.
The interplay between spatiotemporal overlap and morphology as determinants of microstructure suggests no ‘perfect fit’ in a bat-flower network
Authors: Diniz Ugo Mendes , Aguiar Ludmilla Moura de Souza 
Published: February 2023

AbstractPlant–pollinator interactions in diverse tropical communities are often predicted by a combination of ecological variables, yet the interaction drivers between flower-visiting bats and plants at the community level are poorly understood. We assembled a network between Neotropical bats and flowering plants to describe its macrostructure and to test the role of neutral and niche variables in predicting microstructure. We found a moderately generalized network with internally nested modules comprising functionally similar plant and bat species. Modules grouped bats and plants with matching degrees of specialization but had considerable overlap in species morphologies and several inter-module interactions. The spatiotemporal overlap between species, closely followed by morphology, and not abundance, were the best predictors of microstructure, with functional groups of bats also interacting more frequently with plants in certain vegetation types (e.g., frugivores within forests) and seasons (e.g., long-snouted nectarivores in the dry season). Therefore, flower-visiting bats appear to have species-specific niche spaces delimited not only by their ability to exploit certain flower types but also by preferred foraging habitats and the timing of resource availability. The prominent role of resource dissimilarity across vegetation types and seasons likely reflects the heterogeneity of Neotropical savannas, and further research in biomes beyond the Cerrado is needed to better understand the complexity of this system.
Alpha kinase 3 signaling at the M-band maintains sarcomere integrity and proteostasis in striated muscle
Authors: McNamara James W. , Parker Benjamin L. , Voges Holly K. , Mehdiabadi Neda R. , Bolk Francesca , Ahmad Feroz , Chung Jin D. , Charitakis Natalie , Molendijk Jeffrey , Zech Antonia T. L. , Lal Sean , Ramialison Mirana , Karavendzas Kathy , Pointer Hayley L. , Syrris Petros , Lopes Luis R. , Elliott Perry M. , Lynch Gordon S. , Mills Richard J. , Hudson James E. , Watt Kevin I. , Porrello Enzo R. , Elliott David A. 
Published: February 2023

AbstractMuscle contraction is driven by the molecular machinery of the sarcomere. As phosphorylation is a critical regulator of muscle function, the identification of regulatory kinases is important for understanding sarcomere biology. Pathogenic variants in alpha kinase 3 (ALPK3) cause cardiomyopathy and musculoskeletal disease, but little is known about this atypical kinase. Here we show that ALPK3 is an essential component of the M-band of the sarcomere and define the ALPK3-dependent phosphoproteome. ALPK3 deficiency impaired contractility both in human cardiac organoids and in the hearts of mice harboring a pathogenic truncatingAlpk3variant. ALPK3-dependent phosphopeptides were enriched for sarcomeric components of the M-band and the ubiquitin-binding protein sequestosome-1 (SQSTM1) (also known as p62). Analysis of the ALPK3 interactome confirmed binding to M-band proteins including SQSTM1. In human pluripotent stem cell-derived cardiomyocytes modeling cardiomyopathicALPK3mutations, sarcomeric organization and M-band localization of SQSTM1 were abnormal suggesting that this mechanism may underly disease pathogenesis.
TACC3–ch-TOG interaction regulates spindle microtubule assembly by controlling centrosomal recruitment of γ-TuRC
Authors: Rajeev Resmi , Mukhopadhyay Swarnendu , Bhagyanath Suresh , Devu Priya Manu Rani S. , Manna Tapas K. 
Published: February 2023

Abstract
γ-Tubulin ring complex (γ-TuRC), composed of γ-tubulin and multiple γ-tubulin complex proteins (GCPs), serves as the major microtubule nucleating complex in animal cells. However, several γ-TuRC-associated proteins have been shown to control its function. Centrosomal adaptor protein, TACC3, is one such γ-TuRC-interacting factor that is essential for proper mitotic spindle assembly across organisms. ch-TOG is another microtubule assembly promoting protein, which interacts with TACC3 and cooperates in mitotic spindle assembly. However, the mechanism how TACC3–ch-TOG interaction regulates microtubule assembly and the γ-TuRC functions at the centrosomes remain unclear. Here, we show that deletion of the ch-TOG-binding region in TACC3 enhances recruitment of the γ-TuRC proteins to centrosomes and aggravates spindle microtubule assembly in human cells. Loss of TACC3–ch-TOG binding imparts stabilization on TACC3 interaction with the γ-TuRC proteins and it does so by stimulating TACC3 phosphorylation and thereby enhancing phospho-TACC3 recruitment to the centrosomes. We also show that localization of ch-TOG at the centrosomes is substantially reduced and the same on the spindle microtubules is increased in its TACC3-unbound condition. Additional results reveal that ch-TOG depletion stimulates γ-tubulin localization on the spindles without significantly affecting the centrosomal γ-tubulin level. The results indicate that ch-TOG binding to TACC3 controls TACC3 phosphorylation and TACC3-mediated stabilization of the γ-TuRCs at the centrosomes. They also implicate that the spatio-temporal control of TACC3 phosphorylation via ch-TOG-binding ensures mitotic spindle assembly to the optimal level.