bluuebunny/crossref_metadata_2025_split huggingface dataset:
The landscape of alternative polyadenylation in single cells of the developing mouse embryo
Authors: Agarwal Vikram , Lopez-Darwin Sereno , Kelley David R. , Shendure Jay 
Published: August 2021

Abstract3′ untranslated regions (3′ UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3′-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poorly characterized. In this study, we examine a dataset comprising ~2 million nuclei spanning E9.5–E13.5 of mouse embryonic development to quantify transcriptome-wide changes in alternative polyadenylation (APA). We observe a global lengthening of 3′ UTRs across embryonic stages in all cell types, although we detect shorter 3′ UTRs in hematopoietic lineages and longer 3′ UTRs in neuronal cell types within each stage. An analysis of RNA-binding protein (RBP) dynamics identifies ELAV-like family members, which are concomitantly induced in neuronal lineages and developmental stages experiencing 3′-UTR lengthening, as putative regulators of APA. By measuring 3′-UTR isoforms in an expansive single cell dataset, our work provides a transcriptome-wide and organism-wide map of the dynamic landscape of alternative polyadenylation during mammalian organogenesis.
Completely non-fused electron acceptor with 3D-interpenetrated crystalline structure enables efficient and stable organic solar cell
Authors: Ma Lijiao , Zhang Shaoqing , Zhu Jincheng , Wang Jingwen , Ren Junzhen , Zhang Jianqi , Hou Jianhui 
Published: August 2021

AbstractNon-fullerene acceptors (NFAs) based on non-fused conjugated structures have more potential to realize low-cost organic photovoltaic (OPV) cells. However, their power conversion efficiencies (PCEs) are much lower than those of the fused-ring NFAs. Herein, a new bithiophene-based non-fused core (TT-Pi) featuring good planarity as well as large steric hindrance was designed, based on which a completely non-fused NFA, A4T-16, was developed. The single-crystal result of A4T-16 reveals that a three-dimensional interpenetrating network can be formed due to the compact π–π stacking between the adjacent end-capping groups. A high PCE of 15.2% is achieved based on PBDB-TF:A4T-16, which is the highest value for the cells based on the non-fused NFAs. Notably, the device retains ~84% of its initial PCE after 1300 h under the simulated AM 1.5 G illumination (100 mW cm−2). Overall, this work provides insight into molecule design of the non-fused NFAs from the aspect of molecular geometry control.
Cas9-derived peptides presented by MHC Class II that elicit proliferation of CD4+ T-cells
Authors: Simhadri Vijaya L. , Hopkins Louis , McGill Joseph R. , Duke Brian R. , Mukherjee Swati , Zhang Kate , Sauna Zuben E. 
Published: August 2021

AbstractCRISPR–Cas9 mediated genome editing offers unprecedented opportunities for treating human diseases. There are several reports that demonstrate pre-existing immune responses to Cas9 which may have implications for clinical development of CRISPR-Cas9 mediated gene therapy. Here we use 209 overlapping peptides that span the entire sequence of Staphylococcus aureus Cas9 (SaCas9) and human peripheral blood mononuclear cells (PBMCs) from a cohort of donors with a distribution of Major Histocompatibility Complex (MHC) alleles comparable to that in the North American (NA) population to identify the immunodominant regions of the SaCas9 protein. We also use an MHC Associated Peptide Proteomics (MAPPs) assay to identify SaCas9 peptides presented by MHC Class II (MHC-II) proteins on dendritic cells. Using these two data sets we identify 22 SaCas9 peptides that are both presented by MHC-II proteins and stimulate CD4+ T-cells.
Neutralization of MERS coronavirus through a scalable nanoparticle vaccine
Authors: Mohsen Mona O. , Rothen Dominik , Balke Ina , Martina Byron , Zeltina Vilija , Inchakalody Varghese , Gharailoo Zahra , Nasrallah Gheyath , Dermime Said , Tars Kaspars , Vogel Monique , Zeltins Andris , Bachmann Martin F. 
Published: August 2021

AbstractMERS-CoV continues to cause human outbreaks, so far in 27 countries worldwide following the first registered epidemic in Saudi Arabia in 2012. In this study, we produced a nanovaccine based on virus-like particles (VLPs). VLPs are safe vaccine platforms as they lack any replication-competent genetic material, and are used since many years against hepatitis B virus (HBV), hepatitis E virus (HEV) and human papilloma virus (HPV). In order to produce a vaccine that is readily scalable, we genetically fused the receptor-binding motif (RBM) of MERS-CoV spike protein into the surface of cucumber-mosaic virus VLPs. The employed CuMVTT-VLPs represent a new immunologically optimized vaccine platform incorporating a universal T cell epitope derived from tetanus toxin (TT). The resultant vaccine candidate (mCuMVTT-MERS) is a mosaic particle and consists of unmodified wild type monomers and genetically modified monomers displaying RBM, co-assembling within E. coli upon expression. mCuMVTT-MERS vaccine is self-adjuvanted with ssRNA, a TLR7/8 ligand which is spontaneously packaged during the bacterial expression process. The developed vaccine candidate induced high anti-RBD and anti-spike antibodies in a murine model, showing high binding avidity and an ability to completely neutralize MERS-CoV/EMC/2012 isolate, demonstrating the protective potential of the vaccine candidate for dromedaries and humans.
Intrinsic activation of β-catenin signaling by CRISPR/Cas9-mediated exon skipping contributes to immune evasion in hepatocellular carcinoma
Authors: Akasu Masafumi , Shimada Shu , Kabashima Ayano , Akiyama Yoshimitsu , Shimokawa Masahiro , Akahoshi Keiichi , Kudo Atsushi , Yamaoka Shoji , Tanabe Minoru , Tanaka Shinji 
Published: August 2021

AbstractComprehensive analysis of clinical samples has recently identified molecular and immunological classification of hepatocellular carcinoma (HCC), and the CTNNB1 (β-catenin)-mutated subtype exhibits distinctive characteristics of immunosuppressive tumor microenvironment. For clarifying the molecular mechanisms, we first established human and mouse HCC cells with exon 3 skipping of β-catenin, which promoted nuclear translocation and activated the Wnt/β-catenin signaling pathway, by using newly developed multiplex CRISPR/Cas9-based genome engineering system. Gene set enrichment analysis indicated downregulation of immune-associated gene sets in the HCC cells with activated β-catenin signaling. Comparative analysis of gene expression profiles between HCC cells harboring wild-type and exon 3 skipping β-catenin elucidated that the expression levels of four cytokines were commonly decreased in human and mouse β-catenin-mutated HCC cells. Public exome and transcriptome data of 373 human HCC samples showed significant downregulation of two candidate cytokine genes, CCL20 and CXCL2, in HCC tumors with β-catenin hotspot mutations. T cell killing assays and immunohistochemical analysis of grafted tumor tissues demonstrated that the mouse Ctnnb1Δex3 HCC cells evaded immunosurveillance. Taken together, this study discovered that cytokine controlled by β-catenin signaling activation could contribute to immune evasion, and provided novel insights into cancer immunotherapy for the β-catenin-mutated HCC subtype.
Evaluation of a mechanical lung model to test small animal whole body plethysmography
Authors: Hülsmann Swen , Khan Amara , Hagos Liya , Hindermann Martin , Nägel Torsten , Dullin Christian 
Published: August 2021

AbstractWhole-body plethysmography (WBP) is an established method to determine physiological parameters and pathophysiological alteration of breathing in animals and animal models of a variety of diseases. Although frequently used, there is ongoing debate about what exactly is measured by whole-body-plethysmography and how reliable the data derived from this method are. Here, we designed an artificial lung model that enables a thorough evaluation of different predictions about and around whole-body plethysmography. Using our lung model, we confirmed that during WBP two components contribute to the pressure changes detected in the chamber: (1) the increase in the pressure due to heating and moistening of the air during inspiration, termed conditioning; (2) changes in the chamber pressure that depend on airway resistance. Both components overlap and contribute to the temporal pressure-profile measured in the chamber or across the wall of the chamber, respectively. Our data showed that a precise measurement of the breathing volume appears to be hindered by at least two factors: (1) the unknown relative contribution of each of these two components; (2) not only the air in the inspired volume is conditioned during inspiration, but also air within the residual volume and dead space that is recruited during inspiration. Moreover, our data suggest that the expiratory negative pressure peak that is used to determine the enhanced pause (Penh) parameter is not a measure for airway resistance as such but rather a consequence of the animal’s response to the airway resistance, using forced or active expiration to overcome the resistance by a higher thoracic pressure.
State selective fragmentation of doubly ionized sulphur dioxide
Authors: Jarraya M. , Wallner M. , Nyman G. , Yaghlane S. Ben , Hochlaf M. , Eland J. H. D. , Feifel R. 
Published: August 2021

AbstractUsing multi-electron–ion coincidence measurements combined with high level calculations, we show that double ionisation of SO2at 40.81 eV can be state selective. It leads to high energy products, in good yield, via a newly identified mechanism, which is likely to apply widely to multiple ionisation by almost all impact processes.
Ag nanoparticles immobilized on new magnetic alginate halloysite as a recoverable catalyst for reduction of nitroaromatics in aqueous media
Authors: Mohammadi Pourya , Heravi Majid , Daraie Mansoureh 
Published: August 2021

AbstractAmines can be applied in the synthesis of various important compounds such as dyes, drugs, polymers, pharmaceutical products, and biologically active materials. The significant subject in the preparation of amines is the selection of the most effective heterogeneous catalyst to get the best catalytic efficiency, stability, recoverability, and reusability. For this target, we prepared new alginate magnetically recoverable nanocatalyst by stabilization of Ag nanoparticles on the surface of the halloysite (HS) [HS-Alginate-Ag/Fe3O4]. Several detection methods confirmed the production of HS-Alginate-Ag/Fe3O4 nanocatalyst and the results obtained were well explained in the context. HS-Alginate-Ag/Fe3O4 presented good catalytic performance for the hydrogenation of nitro compounds using NaBH4 as the reducing agent and hydrogen donor. The good activity and durability of this catalyst can be attributed to the good dispersion and nano-sized particle of silver nanoparticles.
Establishment and genetic characterization of cell lines derived from proliferating nasal polyps and sinonasal inverted papillomas
Authors: Nukpook Thawaree , Ekalaksananan Tipaya , Kiyono Tohru , Kasemsiri Pornthep , Teeramatwanich Watchareporn , Vatanasapt Patravoot , Chaiwiriyakul Surachat , Ungarreevittaya Piti , Kampan Jureeporn , Muisuk Kanha , Pientong Chamsai 
Published: August 2021

AbstractTo better understand the pathogenesis of nasal polyps (NPs) and sinonasal inverted papillomas (SIPs), we aimed to establish cell lines from fresh tissues of NPs and SIPs and characterize them. Primary cell cultures were obtained from two NP tissues (NP2 and NP3) and one SIP tissue (IP4). All the cells were polygonal in shape, expressed cytokeratin 14, and had normal diploid chromosome status. HPV58 DNA was detected in NP3. To obtain immortal primary cells, NP2 and IP4 cells were transduced with a combination of mutant CDK4, cyclinD1 and TERT. These cells were thereafter named NP2/K4DT and IP4/K4DT, respectively. HPV58-positive NP3 cells were transduced with TERT alone, the resulting cells named NP3/T. Phenotypic and genotypic identity of original tissues and derived cells was investigated. All the cell cultures with transgenes were confirmed to be derived from their parental cells and primary tumor tissues by analysis of short tandem repeats (STR) and maintained in vitro growth, genetic profiles and gene expression characteristics of the primary cells. These virtually immortalized cells, as well as the primary cells, have potential as in vitro models for studying the pathogenesis of NPs and SIPs and for preclinical study to develop new therapeutic agents.
Molecular coupling competing with defects within insulator of the magnetic tunnel junction-based molecular spintronics devices
Authors: Tyagi Pawan , Brown Hayden , Grizzle Andrew , D’Angelo Christopher , Dahal Bishnu R. 
Published: August 2021

AbstractNearly 70 years old dream of incorporating molecule as the device element is still challenged by competing defects in almost every experimentally tested molecular device approach. This paper focuses on the magnetic tunnel junction (MTJ) based molecular spintronics device (MTJMSD) method. An MTJMSD utilizes a tunnel barrier to ensure a robust and mass-producible physical gap between two ferromagnetic electrodes. MTJMSD approach may benefit from MTJ's industrial practices; however, the MTJMSD approach still needs to overcome additional challenges arising from the inclusion of magnetic molecules in conjunction with competing defects. Molecular device channels are covalently bonded between two ferromagnets across the insulating barrier. An insulating barrier may possess a variety of potential defects arising during the fabrication or operational phase. This paper describes an experimental and theoretical study of molecular coupling between ferromagnets in the presence of the competing coupling via an insulating tunnel barrier. We discuss the experimental observations of hillocks and pinhole-type defects producing inter-layer coupling that compete with molecular device elements. We performed theoretical simulations to encompass a wide range of competition between molecules and defects. Monte Carlo Simulation (MCS) was used for investigating the defect-induced inter-layer coupling on MTJMSD. Our research may help understand and design molecular spintronics devices utilizing various insulating spacers such as aluminum oxide (AlOx) and magnesium oxide (MgO) on a wide range of metal electrodes. This paper intends to provide practical insights for researchers intending to investigate the molecular device properties via the MTJMSD approach and do not have a background in magnetic tunnel junction fabrication.
3D printing fluorescent material with tunable optical properties
Authors: Ruiz Alberto J. , Garg Sadhya , Streeter Samuel S. , Giallorenzi Mia K. , LaRochelle Ethan P. M. , Samkoe Kimberley S. , Pogue Brian W. 
Published: August 2021

AbstractThe 3D printing of fluorescent materials could help develop, validate, and translate imaging technologies, including systems for fluorescence-guided surgery. Despite advances in 3D printing techniques for optical targets, no comprehensive method has been demonstrated for the simultaneous incorporation of fluorophores and fine-tuning of absorption and scattering properties. Here, we introduce a photopolymer-based 3D printing method for manufacturing fluorescent material with tunable optical properties. The results demonstrate the ability to 3D print various individual fluorophores at reasonably high fluorescence yields, including IR-125, quantum dots, methylene blue, and rhodamine 590. Furthermore, tuning of the absorption and reduced scattering coefficients is demonstrated within the relevant mamalian soft tissue coefficient ranges of 0.005–0.05 mm−1 and 0.2–1.5 mm−1, respectively. Fabrication of fluorophore-doped biomimicking and complex geometric structures validated the ability to print feature sizes less than 200 μm. The presented methods and optical characterization techniques provide the foundation for the manufacturing of solid 3D printed fluorescent structures, with direct relevance to biomedical optics and the broad adoption of fast manufacturing methods in fluorescence imaging.
Ternary optimization for designing metasurfaces
Authors: Hojjati Azin , Soleimani Mohammad , Nayyeri Vahid , Ramahi Omar M. 
Published: August 2021

AbstractA fully automated approach for designing metasurfaces whose unit cell may include metallic vias is proposed. Towards this aim, a ternary version of the particle swarm optimization (PSO) algorithm is employed in order to find the optimal metallic pattern and via-hole positions simultaneously. In the proposed design method, the upper surface of the unit cell is first pixelated. One of the possible three states of a metallic covered pixel, an uncovered etched pixel and a pixel containing a centered metalized via-hole is assigned to each pixel. The optimal state of each pixel is then determined by utilizing a ternary PSO algorithm to achieve favorable design goals. This method can be used for designing various metasurfaces as well as other via-assisted electromagnetic structures. As a proof of concept, the proposed method was applied to design two surfaces: a frequency selective surface with a minimum resonance frequency, and a linear-to-circular polarization converter with a maximum polarization conversion bandwidth. Comparison of the results with previous works confirms the efficiency and capability of the proposed method to design diverse metasurfaces in an automated fashion without the need for any theoretical or physical model.
Decreased PGC1β expression results in disrupted human erythroid differentiation, impaired hemoglobinization and cell cycle exit
Authors: Sen Taha , Chen Jun , Singbrant Sofie 
Published: August 2021

AbstractProduction of red blood cells relies on proper mitochondrial function, both for their increased energy demands during differentiation and for proper heme and iron homeostasis. Mutations in genes regulating mitochondrial function have been reported in patients with anemia, yet their pathophysiological role often remains unclear. PGC1β is a critical coactivator of mitochondrial biogenesis, with increased expression during terminal erythroid differentiation. The role of PGC1β has however mainly been studied in skeletal muscle, adipose and hepatic tissues, and its function in erythropoiesis remains largely unknown. Here we show that perturbed PGC1β expression in human hematopoietic stem/progenitor cells from both bone marrow and cord blood results in impaired formation of early erythroid progenitors and delayed terminal erythroid differentiation in vitro, with accumulations of polychromatic erythroblasts, similar to MDS-related refractory anemia. Reduced levels of PGC1β resulted in deregulated expression of iron, heme and globin related genes in polychromatic erythroblasts, and reduced hemoglobin content in the more mature bone marrow derived reticulocytes. Furthermore, PGC1β knock-down resulted in disturbed cell cycle exit with accumulation of erythroblasts in S-phase and enhanced expression of G1-S regulating genes, with smaller reticulocytes as a result. Taken together, we demonstrate that PGC1β is directly involved in production of hemoglobin and regulation of G1-S transition and is ultimately required for proper terminal erythroid differentiation.
Impact of genetic and non-genetic factors on hepatic CYP2C9 expression and activity in Hungarian subjects
Authors: Fekete Ferenc , Mangó Katalin , Déri Máté , Incze Evelyn , Minus Annamária , Monostory Katalin 
Published: August 2021

AbstractCYP2C9, one of the most abundant hepatic cytochrome P450 enzymes, is involved in metabolism of 15–20% of clinically important drugs (warfarin, sulfonylureas, phenytoin, non-steroid anti-inflammatory drugs). To avoid adverse events and/or impaired drug-response, CYP2C9 pharmacogenetic testing is recommended. The impact of CYP2C9 polymorphic alleles (CYP2C9*2, CYP2C9*3) and phenoconverting non-genetic factors on CYP2C9 function and expression was investigated in liver tissues from Caucasian subjects (N = 164). The presence of CYP2C9*3 allele was associated with CYP2C9 functional impairment, and CYP2C9*2 influenced tolbutamide 4′-hydroxylase activity only in subjects with two polymorphic alleles, whereas the contribution of CYP2C8*3 was not confirmed. In addition to CYP2C9 genetic polymorphisms, non-genetic factors (co-medication with CYP2C9-specific inhibitors/inducers and non-specific factors including amoxicillin + clavulanic acid therapy or chronic alcohol consumption) contributed to the prediction of hepatic CYP2C9 activity; however, a CYP2C9 genotype–phenotype mismatch still existed in 32.6% of the subjects. Substantial variability in CYP2C9 mRNA levels, irrespective of CYP2C9 genotype, was demonstrated; however, CYP2C9 induction and non-specific non-genetic factors potentially resulting in liver injury appeared to modify CYP2C9 expression. In conclusion, complex implementation of CYP2C9 genotype and non-genetic factors for the most accurate estimation of hepatic CYP2C9 activity may improve efficiency and safety of medication with CYP2C9 substrate drugs in clinical practice.
Heat hardening enhances mitochondrial potential for respiration and oxidative defence capacity in the mantle of thermally stressed Mytilus galloprovincialis
Authors: Georgoulis Ioannis , Feidantsis Konstantinos , Giantsis Ioannis A. , Kakale Asimina , Bock Christian , Pörtner Hans O. , Sokolova Inna M. , Michaelidis Basile 
Published: August 2021

AbstractEctotherms are exposed to a range of environmental temperatures and may face extremes beyond their upper thermal limits. Such temperature extremes can stimulate aerobic metabolism toward its maximum, a decline in aerobic substrate oxidation, and a parallel increase of anaerobic metabolism, combined with ROS generation and oxidative stress. Under these stressful conditions, marine organisms recruit several defensive strategies for their maintenance and survival. However, thermal tolerance of ectothermic organisms may be increased after a brief exposure to sub-lethal temperatures, a process known as "hardening". In our study, we examined the ability ofM. galloprovincialisto increase its thermal tolerance under the effect of elevated temperatures (24, 26 and 28 °C) through the "hardening" process. Our results demonstrate that this process can increase the heat tolerance and antioxidant defense of heat hardened mussels through more efficient ETS activity when exposed to temperatures beyond 24 °C, compared to non-hardened individuals. Enhanced cell protection is reflected in better adaptive strategies of heat hardened mussels, and thus decreased mortality. Although hardening seems a promising process for the maintenance of aquacultured populations under increased seasonal temperatures, further investigation of the molecular and cellular mechanisms regulating mussels’ heat resistance is required.