bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using MARSIS signal attenuation to assess the presence of South Polar Layered Deposit subglacial brines
Authors: Lauro Sebastian E. , Pettinelli Elena , Caprarelli Graziella , Baniamerian Jamaledin , Mattei Elisabetta , Cosciotti Barbara , Stillman David E. , Primm Katherine M. , Soldovieri Francesco , Orosei Roberto 
Published: September 2022

AbstractKnowledge of the physical and thermal properties of the South Polar Layer Deposits (SPLD) is key to constrain the source of bright basal reflections at Ultimi Scopuli detected by the MARSIS (Mars Advanced Radar for Subsurface and Ionosphere Sounding) radar sounder. Here we present a detailed analysis of attenuation, based on data acquired by MARSIS at 3, 4, and 5 MHz. We show that attenuation is frequency dependent, and that its behavior is consistent throughout the entire region. This suggests that the SPLD are compositionally homogeneous at Ultimi Scopuli, and our results are consistent with dust contents of 5 to 12%. Using these values as input, and plausible estimates of surface temperature and heat flux, we inferred basal temperatures around 200 K: these are consistent with perchlorate brines within liquid vein networks as the source of the reflections. Furthermore, extrapolation of the attenuation to higher frequencies explains why SHARAD (Shallow Radar) has thus far not detected basal reflections within the SPLD at Ultimi Scopuli.
Tri-explosophoric groups driven fused energetic heterocycles featuring superior energetic and safety performances outperforms HMX
Authors: Li Jie , Liu Yubing , Ma Wenqi , Fei Teng , He Chunlin , Pang Siping 
Published: September 2022

AbstractThe design and synthesis of novel energetic compounds with integrated properties of high density, high energy, good thermal stability and sensitivities is particularly challenging due to the inherent contradiction between energy and safety for energetic compounds. In this study, a novel structure of 4-amino-7,8-dinitropyrazolo-[5,1-d] [1,2,3,5]-tetrazine 2-oxide (BITE-101) is designed and synthesized in three steps. With the help of the complementary advantages of different explosophoric groups and diverse weak interactions, BITE-101 is superior to the benchmark explosive HMX in all respects, including higher density of 1.957 g·cm−3, highest decomposition temperature of 295 °C (onset) among CHON-based high explosives to date and superior detonation velocity and pressure (D: 9314 m·s−1, P: 39.3 GPa), impact and friction sensitivities (IS: 18 J, FS: 128 N), thereby showing great potential for practical application as replacement for HMX, the most powerful military explosive in current use.
In vivo self-assembled siRNA as a modality for combination therapy of ulcerative colitis
Authors: Zhou Xinyan , Yu Mengchao , Ma Luzhen , Fu Jinyu , Guo Jingwei , Lei Jieqiong , Fu Zheng , Fu Yong , Zhang Qipeng , Zhang Chen-Yu , Chen Xi 
Published: September 2022

AbstractGiven the complex nature of ulcerative colitis, combination therapy targeting multiple pathogenic genes and pathways of ulcerative colitis may be required. Unfortunately, current therapeutic strategies are usually based on independent chemical compounds or monoclonal antibodies, and the full potential of combination therapy has not yet been realized for the treatment of ulcerative colitis. Here, we develop a synthetic biology strategy that integrates the naturally existing circulating system of small extracellular vesicles with artificial genetic circuits to reprogram the liver of male mice to self-assemble multiple siRNAs into secretory small extracellular vesicles and facilitate in vivo delivery siRNAs through circulating small extracellular vesicles for the combination therapy of mouse models of ulcerative colitis. Particularly, repeated injection of the multi-targeted genetic circuit designed for simultaneous inhibition of TNF-α, B7-1 and integrin α4 rapidly relieves intestinal inflammation and exerts a synergistic therapeutic effect against ulcerative colitis through suppressing the pro-inflammatory cascade in colonic macrophages, inhibiting the costimulatory signal to T cells and blocking T cell homing to sites of inflammation. More importantly, we design an AAV-driven genetic circuit to induce substantial and lasting inhibition of TNF-α, B7-1 and integrin α4 through only a single injection. Overall, this study establishes a feasible combination therapeutic strategy for ulcerative colitis, which may offer an alternative to conventional biological therapies requiring two or more independent compounds or antibodies.
TFEB regulates sulfur amino acid and coenzyme A metabolism to support hepatic metabolic adaptation and redox homeostasis
Authors: Matye David , Gunewardena Sumedha , Chen Jianglei , Wang Huaiwen , Wang Yifeng , Hasan Mohammad Nazmul , Gu Lijie , Clayton Yung Dai , Du Yanhong , Chen Cheng , Friedman Jacob E. , Lu Shelly C. , Ding Wen-Xing , Li Tiangang 
Published: September 2022

AbstractFatty liver is a highly heterogenous condition driven by various pathogenic factors in addition to the severity of steatosis. Protein insufficiency has been causally linked to fatty liver with incompletely defined mechanisms. Here we report that fatty liver is a sulfur amino acid insufficient state that promotes metabolic inflexibility via limiting coenzyme A availability. We demonstrate that the nutrient-sensing transcriptional factor EB synergistically stimulates lysosome proteolysis and methionine adenosyltransferase to increase cysteine pool that drives the production of coenzyme A and glutathione, which support metabolic adaptation and antioxidant defense during increased lipid influx. Intriguingly, mice consuming an isocaloric protein-deficient Western diet exhibit selective hepatic cysteine, coenzyme A and glutathione deficiency and acylcarnitine accumulation, which are reversed by cystine supplementation without normalizing dietary protein intake. These findings support a pathogenic link of dysregulated sulfur amino acid metabolism to metabolic inflexibility that underlies both overnutrition and protein malnutrition-associated fatty liver development.
Anomalous Josephson coupling and high-harmonics in non-centrosymmetric superconductors with S-wave spin-triplet pairing
Authors: Fukaya Yuri , Tanaka Yukio , Gentile Paola , Yada Keiji , Cuoco Mario 
Published: September 2022

AbstractWe study the Josephson effects arising in junctions made of non-centrosymmetric superconductors with spin-triplet pairing having s-wave orbital-singlet symmetry. We demonstrate that the orbital dependent character of the spin-triplet order parameter determines its non-trivial texture in the momentum space due to the inversion symmetry breaking and spin-orbit interactions. The emergence of this pattern is responsible for the occurrence of an anomalous Josephson coupling and a dominance of high-harmonics in the current phase relation. Remarkably, due to the spin-orbital couplings, variations in the electronic structure across the heterostructure can generally turn the ground state of the junction from 0- to a generic value of the Josephson phase, thus realizing the so-called φ-junction. Hallmarks of the resulting Josephson behavior, apart from non-standard current-phase relation, are provided by an unconventional temperature and magnetic field dependence of the critical current. These findings indicate the path for the design of superconducting orbitronics devices and account for several observed anomalies of the supercurrent in oxide interface superconductors.
De novo metatranscriptomic exploration of gene function in the millipede holobiont
Authors: Sardar Puspendu , Šustr Vladimír , Chroňáková Alica , Lorenc František , Faktorová Lucie 
Published: September 2022

AbstractInvertebrate–microbial associations are widespread in the biosphere and are often related to the function of novel genes, fitness advantages, and even speciation events. Despite ~ 13,000 species of millipedes identified across the world, millipedes and their gut microbiota are markedly understudied compared to other arthropods. Exploring the contribution of individual host-associated microbes is often challenging as many are uncultivable. In this study, we conducted metatranscriptomic profiling of different body segments of a millipede at the holobiont level. This is the first reported transcriptome assembly of a tropical millipedeTelodeinopus aoutii(Demange, 1971), as well as the first study on any Myriapoda holobiont. High-throughput RNA sequencing revealed thatTelodeinopus aoutiicontained > 90% of the core Arthropoda genes. Proteobacteria, Bacteroidetes, Firmicutes, and Euryarchaeota represented dominant and functionally active phyla in the millipede gut, among which 97% of Bacteroidetes and 98% of Firmicutes were present exclusively in the hindgut. A total of 37,831 predicted protein-coding genes of millipede holobiont belonged to six enzyme classes. Around 35% of these proteins were produced by microbiota in the hindgut and 21% by the host in the midgut. Our results indicated that although major metabolic pathways operate at the holobiont level, the involvement of some host and microbial genes are mutually exclusive and microbes predominantly contribute to essential amino acid biosynthesis, short-chain fatty acid metabolism, and fermentation.
Profiling development of abdominal organs in the pig
Authors: Gabriel George C. , Devine William A. , Redel Bethany K. , Whitworth Kristin M. , Samuel Melissa , Spate Lee D. , Cecil Raissa F. , Prather Randall S. , Wu Yijen L. , Wells Kevin D. , Lo Cecilia W. 
Published: September 2022

AbstractThe pig is an ideal model system for studying human development and disease due to its similarities to human anatomy, physiology, size, and genome. Further, advances in CRISPR gene editing have made genetically engineered pigs viable models for the study of human pathologies and congenital anomalies. However, a detailed atlas illustrating pig development is necessary for identifying and modeling developmental defects. Here we describe normal development of the pig abdominal system and show examples of congenital defects that can arise in CRISPR gene edited SAP130 mutant pigs. Normal pigs at different gestational ages from day 20 (D20) to term were examined and the configuration of the abdominal organs was studied using 3D histological reconstructions with episcopic confocal microscopy, magnetic resonance imaging (MRI) and necropsy. This revealed prominent mesonephros, a transient embryonic organ present only during embryogenesis, at D20, while the developing metanephros that will form the permanent kidney are noted at D26. By D64 the mesonephroi are absent and only the metanephroi remain. The formation of the liver and pancreas was observed by D20 and complete by D30 and D35 respectively. The spleen and adrenal glands are first identified at D26 and completed by D42. The developing bowel and the gonads are identified at D20. The bowel appears completely rotated by D42, and testes in the male were descended at D64. This atlas and the methods used are excellent tools for identifying developmental pathologies of the abdominal organs in the pig at different stages of development.
Predicting potential global and future distributions of the African armyworm (Spodoptera exempta) using species distribution models
Authors: Gómez-Undiano Irene , Musavi Francis , Mushobozi Wilfred L. , David Grace M. , Day Roger , Early Regan , Wilson Kenneth 
Published: September 2022

AbstractInvasive species have historically been a problem derived from global trade and transport. To aid in the control and management of these species, species distribution models (SDMs) have been used to help predict possible areas of expansion. Our focal organism, the African Armyworm (AAW), has historically been known as an important pest species in Africa, occurring at high larval densities and causing outbreaks that can cause enormous economic damage to staple crops. The goal of this study is to map the AAW’s present and potential distribution in three future scenarios for the region, and the potential global distribution if the species were to invade other territories, using 40 years of data on more than 700 larval outbreak reports from Kenya and Tanzania. The present distribution in East Africa coincides with its previously known distribution, as well as other areas of grassland and cropland, which are the host plants for this species. The different future climatic scenarios show broadly similar potential distributions in East Africa to the present day. The predicted global distribution shows areas where the AAW has already been reported, but also shows many potential areas in the Americas where, if transported, environmental conditions are suitable for AAW to thrive and where it could become an invasive species.
Pseudotime analysis reveals novel regulatory factors for multigenic onset and monogenic transition of odorant receptor expression
Authors: Hussainy Mohammad , Korsching Sigrun I. , Tresch Achim 
Published: September 2022

AbstractDuring their maturation from horizontal basal stem cells, olfactory sensory neurons (OSNs) are known to select exactly one out of hundreds of olfactory receptors (ORs) and express it on their surface, a process called monogenic selection. Monogenic expression is preceded by a multigenic phase during which several OR genes are expressed in a single OSN. Here, we perform pseudotime analysis of a single cell RNA-Seq dataset of murine olfactory epithelium to precisely align the multigenic and monogenic expression phases with the cell types occurring during OSN differentiation. In combination with motif analysis of OR gene cluster-associated enhancer regions, we identify known and novel transcription (co-)factors (Ebf1, Lhx2, Ldb1, Fos and Ssbp2) and chromatin remodelers (Kdm1a, Eed and Zmynd8) associated with OR expression. The inferred temporal order of their activity suggests novel mechanisms contributing to multigenic OR expression and monogenic selection.
Identification of a prognosis-related ceRNA network in cholangiocarcinoma and potentially therapeutic molecules using a bioinformatic approach and molecular docking
Authors: Gao Xiaoling , Zhang Wenhao , Jia Yanjuan , Xu Hui , Zhu Yuchen , Pei Xiong 
Published: September 2022

AbstractCholangiocarcinoma (CCA) is a highly malignant disease with a poor prognosis, and mechanisms of initiation and development are not well characterized. It is long noncoding RNAs (lncRNAs) acting as miRNA decoys to regulate cancer-related RNAs in competing endogenous RNA (ceRNA) networks that suggest a possible molecular mechanism in CCA. The current study aims to find potential prognosis biomarkers and small molecule therapeutic targets based on the construction of a CCA prognosis-related ceRNA network. A transcriptome dataset for CCA was downloaded from the TCGA database. Differentially expressed lncRNAs (DElncRNAs), DEmiRNAs and DEmRNAs were identified based on the differential expression and a DEceRNA network was constructed using predicted miRNA-lncRNA and miRNA-mRNA interactions. Heat maps, PCA analysis, and Pathway enrichment analysis and GO enrichment analysis were conducted. The prognostic risk model and molecular docking were constructed based on identified key ceRNA networks. A DElncRNA-miRNA-mRNAs network consisting of 434 lncRNA-miRNA pairs and 284 miRNA-mRNA pairs with 200 lncRNAs, 21 miRNAs, and 245 mRNAs was constructed. There were three lncRNAs (AC090772.1, LINC00519, and THAP7-AS1) and their downstream mRNAs (MECOM, MBNL3, RCN2) screened out as prognostic factors in CAA. Three key networks (LINC00519/ hsa-mir-22/ MECOM, THAP7-AS1/hsa-mir-155/MBNL3, and THAP7-AS1/hsa-mir-155/RCN2) were identified based on binding sites prediction and survival analysis. A prognostic risk model was established with a good predictive ability (AUC = 0.66–0.83). Four anticancer small molecules, MECOM and 17-alpha-estradiol (−7.1 kcal/mol), RCN2 and emodin (−8.3 kcal/mol), RCN2 and alpha-tocopherol (−5.6 kcal/mol), and MBNL3 and 17-beta-estradiol (−7.1 kcal/mol) were identified. Based on the DEceRNA network and Kaplan–Meier survival analysis, we identified three important ceRNA networks associated with the poor prognosis of CCA. Four anti-cancer small molecules were screened out by computer-assisted drug screening as potential small molecules for the treatment of CCA. This study provides theoretical support for the development of ceRNA network-based drugs to improve the prognosis of CCA.
Deep learning alignment of bidirectional raster scanning in high speed photoacoustic microscopy
Authors: Kim Jongbeom , Lee Dongyoon , Lim Hyokyung , Yang Hyekyeong , Kim Jaewoo , Kim Jeesu , Kim Yeonggeun , Kim Hyung Ham , Kim Chulhong 
Published: September 2022

AbstractSimultaneous point-by-point raster scanning of optical and acoustic beams has been widely adapted to high-speed photoacoustic microscopy (PAM) using a water-immersible microelectromechanical system or galvanometer scanner. However, when using high-speed water-immersible scanners, the two consecutively acquired bidirectional PAM images are misaligned with each other because of unstable performance, which causes a non-uniform time interval between scanning points. Therefore, only one unidirectionally acquired image is typically used; consequently, the imaging speed is reduced by half. Here, we demonstrate a scanning framework based on a deep neural network (DNN) to correct misaligned PAM images acquired via bidirectional raster scanning. The proposed method doubles the imaging speed compared to that of conventional methods by aligning nonlinear mismatched cross-sectional B-scan photoacoustic images during bidirectional raster scanning. Our DNN-assisted raster scanning framework can further potentially be applied to other raster scanning-based biomedical imaging tools, such as optical coherence tomography, ultrasound microscopy, and confocal microscopy.
Genome-wide identification and development of miniature inverted-repeat transposable elements and intron length polymorphic markers in tea plant (Camellia sinensis)
Authors: Rohilla Megha , Mazumder Abhishek , Saha Dipnarayan , Pal Tarun , Begam Shbana , Mondal Tapan Kumar 
Published: September 2022

AbstractMarker-assisted breeding and tagging of important quantitative trait loci for beneficial traits are two important strategies for the genetic improvement of plants. However, the scarcity of diverse and informative genetic markers covering the entire tea genome limits our ability to achieve such goals. In the present study, we used a comparative genomic approach to mine the tea genomes of Camellia sinensis var. assamica (CSA) and C. sinensis var. sinensis (CSS) to identify the markers to differentiate tea genotypes. In our study, 43 and 60 Camellia sinensis miniature inverted-repeat transposable element (CsMITE) families were identified in these two sequenced tea genomes, with 23,170 and 37,958 putative CsMITE sequences, respectively. In addition, we identified 4912 non-redundant, Camellia sinensis intron length polymorphic (CsILP) markers, 85.8% of which were shared by both the CSS and CSA genomes. To validate, a subset of randomly chosen 10 CsMITE markers and 15 CsILP markers were tested and found to be polymorphic among the 36 highly diverse tea genotypes. These genome-wide markers, which were identified for the first time in tea plants, will be a valuable resource for genetic diversity analysis as well as marker-assisted breeding of tea genotypes for quality improvement.
Clinical and NGS predictors of response to regorafenib in recurrent glioblastoma
Authors: Chiesa Silvia , Mangraviti Antonella , Martini Maurizio , Cenci Tonia , Mazzarella Ciro , Gaudino Simona , Bracci Serena , Martino Antonella , Della Pepa Giuseppe M. , Offi Martina , Gessi Marco , Russo Rosellina , Martucci Matia , Beghella Bartoli Francesco , Larocca Luigi M. , Lauretti Liverana , Olivi Alessandro , Pallini Roberto , Balducci Mario , D’Alessandris Quintino Giorgio 
Published: September 2022

AbstractPredictive factors for response to regorafenib in recurrent glioblastoma, IDH-wildtype, are scarcely recognized. The objective of this study was to identify molecular predictive factors for response to regorafenib using a clinically available platform. We analyzed a prospective cohort of 30 patients harboring recurrent glioblastoma, IDH-wildtype, and treated with regorafenib. Next-generation sequencing (NGS) analysis was performed on DNA extracted from paraffin-embedded tissues using a clinically available platform. Moreover, MGMT methylation and EGFRvIII expression analyses were performed. Six-month progression-free survival (PFS) was 30% and median overall survival (OS) was 7.5 months, in line with literature data. NGS analysis revealed a mutation in the EGFR pathway in 18% of cases and a mutation in the mitogen-activated protein-kinase (MAPK) pathway in 18% of cases. In the remaining cases, no mutations were detected. Patients carrying MAPK pathway mutation had a poor response to regorafenib treatment, with a significantly shorter PFS and a nonsignificantly shorter OS compared to EGFR-mutated patients (for PFS, 2.5 vs 4.5 months, p = 0.0061; for OS, 7 vs 9 months, p = 0.1076). Multivariate analysis confirmed that MAPK pathway mutations independently predicted a shorter PFS after regorafenib treatment (p = 0.0188). The negative prognostic role of MAPK pathway alteration was reinforced when we combined EGFR-mutated with EGFRvIII-positive cases. Recurrent glioblastoma tumors with an alteration in MAPK pathway could belong to the mesenchymal subtype and respond poorly to regorafenib treatment, while EGFR-altered cases have a better response to regorafenib. We thus provide a molecular selection criterion easy to implement in the clinical practice.
Identification of stable housekeeping genes for induced pluripotent stem cells and -derived endothelial cells for drug testing
Authors: Ong Sheena L. M. , Baelde Hans J. , van IJzendoorn David G. P. , Bovée Judith V. M. G. , Szuhai Karoly 
Published: September 2022

AbstractThere are no validated housekeeping genes in induced pluripotent stem cells (iPSC) and derived endothelial iPSC (iPSC-EC). Thus a comparison of gene expression levels is less reliable, especially during drug treatments. Here, we utilized transcriptome sequencing data of iPSC and iPSC-EC with or without CRISPR-Cas9 induced translocation to identify a panel of 15 candidate housekeeping genes. For comparison, five commonly used housekeeping genes (B2M, GAPDH, GUSB, HMBS, and HPRT1) were included in the study. The panel of 20 candidate genes were investigated for their stability as reference genes. This panel was analyzed and ranked based on stability using five algorithms, delta-Ct, bestkeeper, geNorm, Normfinder, and Reffinder. Based on the comprehensive ranking of Reffinder, the stability of the top two genes—RPL36AL and TMBIM6, and the bottom two genes—UBA1 and B2M, were further studied in iPSC-EC with and without genetic manipulation, and after treatment with telatinib. Using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), it was shown that gene expression of the top two housekeeping genes, RPL36AL and TMBIM6, remained stable during drug treatment. We identified a panel of housekeeping genes that could be utilized in various conditions using iPSC and iPSC-derived endothelial cells as well as genetically modified iPSC for drug treatment.