bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rescue of mitochondrial import failure by intercellular organellar transfer
Authors: Needs Hope I. , Glover Emily , Pereira Gonçalo C. , Witt Alina , Hübner Wolfgang , Dodding Mark P. , Henley Jeremy M. , Collinson Ian 
Published: February 2024

AbstractMitochondria are the powerhouses of eukaryotic cells, composed mostly of nuclear-encoded proteins imported from the cytosol. Thus, problems with the import machinery will disrupt their regenerative capacity and the cell’s energy supplies – particularly troublesome for energy-demanding cells of nervous tissue and muscle. Unsurprisingly then, import breakdown is implicated in disease. Here, we explore the consequences of import failure in mammalian cells; wherein, blocking the import machinery impacts mitochondrial ultra-structure and dynamics, but, surprisingly, does not affect import. Our data are consistent with a response involving intercellular mitochondrial transport via tunnelling nanotubes to import healthy mitochondria and jettison those with blocked import sites. These observations support the existence of a widespread mechanism for the rescue of mitochondrial dysfunction.
An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission
Authors: Adler Julia M. , Martin Vidal Ricardo , Langner Christine , Vladimirova Daria , Abdelgawad Azza , Kunecova Daniela , Lin Xiaoyuan , Nouailles Geraldine , Voss Anne , Kunder Sandra , Gruber Achim D. , Wu Haibo , Osterrieder Nikolaus , Kunec Dusan , Trimpert Jakob 
Published: February 2024

AbstractThe development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways—the primary site of infection and virus shedding. Here we compare the efficacy of a mucosal, replication-competent yet fully attenuated virus vaccine, sCPD9-ΔFCS, and the monovalent mRNA vaccine BNT162b2 in preventing transmission of SARS-CoV-2 variants B.1 and Omicron BA.5 in two scenarios. Firstly, we assessed the protective efficacy of the vaccines by exposing vaccinated male Syrian hamsters to infected counterparts. Secondly, we evaluated transmission of the challenge virus from vaccinated and subsequently challenged male hamsters to naïve contacts. Our findings demonstrate that the live-attenuated vaccine (LAV) sCPD9-ΔFCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios. Our results provide evidence for the advantages of locally administered LAVs over intramuscularly administered mRNA vaccines in preventing infection and reducing virus transmission.
Dysfunction of duplicated pair rice histone acetyltransferases causes segregation distortion and an interspecific reproductive barrier
Authors: Liao Ben , Xiang You-Huang , Li Yan , Yang Kai-Yang , Shan Jun-Xiang , Ye Wang-Wei , Dong Nai-Qian , Kan Yi , Yang Yi-Bing , Zhao Huai-Yu , Yu Hong-Xiao , Lu Zi-Qi , Zhao Yan , Zhao Qiang , Guo Dongling , Guo Shuang-Qin , Lei Jie-Jie , Mu Xiao-Rui , Cao Ying-Jie , Han Bin , Lin Hong-Xuan 
Published: February 2024

AbstractPostzygotic reproductive isolation, which results in the irreversible divergence of species, is commonly accompanied by hybrid sterility, necrosis/weakness, or lethality in the F1 or other offspring generations. Here we show that the loss of function of HWS1 and HWS2, a couple of duplicated paralogs, together confer complete interspecific incompatibility between Asian and African rice. Both of these non-Mendelian determinants encode the putative Esa1-associated factor 6 (EAF6) protein, which functions as a characteristic subunit of the histone H4 acetyltransferase complex regulating transcriptional activation via genome-wide histone modification. The proliferating tapetum and inappropriate polar nuclei arrangement cause defective pollen and seeds in F2 hybrid offspring due to the recombinant HWS1/2-mediated misregulation of vitamin (biotin and thiamine) metabolism and lipid synthesis. Evolutionary analysis of HWS1/2 suggests that this gene pair has undergone incomplete lineage sorting (ILS) and multiple gene duplication events during speciation. Our findings have not only uncovered a pair of speciation genes that control hybrid breakdown but also illustrate a passive mechanism that could be scaled up and used in the guidance and optimization of hybrid breeding applications for distant hybridization.
Mutation-specific CAR T cells as precision therapy for IGLV3-21R110 expressing high-risk chronic lymphocytic leukemia
Authors: Märkl Florian , Schultheiß Christoph , Ali Murtaza , Chen Shih-Shih , Zintchenko Marina , Egli Lukas , Mietz Juliane , Chijioke Obinna , Paschold Lisa , Spajic Sebastijan , Holtermann Anne , Dörr Janina , Stock Sophia , Zingg Andreas , Läubli Heinz , Piseddu Ignazio , Anz David , Minden Marcus Dühren-von , Zhang Tianjiao , Nerreter Thomas , Hudecek Michael , Minguet Susana , Chiorazzi Nicholas , Kobold Sebastian , Binder Mascha 
Published: February 2024

AbstractThe concept of precision cell therapy targeting tumor-specific mutations is appealing but requires surface-exposed neoepitopes, which is a rarity in cancer. B cell receptors (BCR) of mature lymphoid malignancies are exceptional in that they harbor tumor-specific-stereotyped sequences in the form of point mutations that drive self-engagement of the BCR and autologous signaling. Here, we use a BCR light chain neoepitope defined by a characteristic point mutation (IGLV3-21R110) for selective targeting of a poor-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. We develop murine and humanized CAR constructs expressed in T cells from healthy donors and CLL patients that eradicate IGLV3-21R110 expressing cell lines and primary CLL cells, but neither cells expressing the non-pathogenic IGLV3-21G110 light chain nor polyclonal healthy B cells. In vivo experiments confirm epitope-selective cytolysis in xenograft models in female mice using engrafted IGLV3-21R110 expressing cell lines or primary CLL cells. We further demonstrate in two humanized mouse models lack of cytotoxicity towards human B cells. These data provide the basis for advanced approaches of resistance-preventive and biomarker-guided cellular targeting of functionally relevant lymphoma driver mutations sparing normal B cells.
Optimizing potassium polysulfides for high performance potassium-sulfur batteries
Authors: Song Wanqing , Yang Xinyi , Zhang Tao , Huang Zechuan , Wang Haozhi , Sun Jie , Xu Yunhua , Ding Jia , Hu Wenbin 
Published: February 2024

AbstractPotassium-sulfur batteries attract tremendous attention as high-energy and low-cost energy storage system, but achieving high utilization and long-term cycling of sulfur remains challenging. Here we show a strategy of optimizing potassium polysulfides for building high-performance potassium-sulfur batteries. We design the composite of tungsten single atom and tungsten carbide possessing potassium polysulfide migration/conversion bi-functionality by theoretical screening. We create two ligand environments for tungsten in the metal-organic framework, which respectively transmute into tungsten single atom and tungsten carbide nanocrystals during pyrolysis. Tungsten carbide provide catalytic sites for potassium polysulfides conversion, while tungsten single atoms facilitate sulfides migration thereby significantly alleviating the insulating sulfides accumulation and the associated catalytic poisoning. Resultantly, highly efficient potassium-sulfur electrochemistry is achieved under high-rate and long-cycling conditions. The batteries deliver 89.8% sulfur utilization (1504 mAh g−1), superior rate capability (1059 mAh g−1 at 1675 mA g−1) and long lifespan of 200 cycles at 25 °C. These advances enlighten direction for future KSBs development.
No ground truth needed: unsupervised sinogram inpainting for nanoparticle electron tomography (UsiNet) to correct missing wedges
Authors: Yao Lehan , Lyu Zhiheng , Li Jiahui , Chen Qian 
Published: February 2024

AbstractComplex natural and synthetic materials, such as subcellular organelles, device architectures in integrated circuits, and alloys with microstructural domains, require characterization methods that can investigate the morphology and physical properties of these materials in three dimensions (3D). Electron tomography has unparalleled (sub-)nm resolution in imaging 3D morphology of a material, critical for charting a relationship among synthesis, morphology, and performance. However, electron tomography has long suffered from an experimentally unavoidable missing wedge effect, which leads to undesirable and sometimes extensive distortion in the final reconstruction. Here we develop and demonstrate Unsupervised Sinogram Inpainting for Nanoparticle Electron Tomography (UsiNet) to correct missing wedges. UsiNet is the first sinogram inpainting method that can be realistically used for experimental electron tomography by circumventing the need for ground truth. We quantify its high performance using simulated electron tomography of nanoparticles (NPs). We then apply UsiNet to experimental tomographs, where >100 decahedral NPs and vastly different byproduct NPs are simultaneously reconstructed without missing wedge distortion. The reconstructed NPs are sorted based on their 3D shapes to understand the growth mechanism. Our work presents UsiNet as a potent tool to advance electron tomography, especially for heterogeneous samples and tomography datasets with large missing wedges, e.g. collected for beam sensitive materials or during temporally-resolved in-situ imaging.
miR-Blood – a small RNA atlas of human blood components
Authors: Jehn Julia , Trudzinski Franziska , Horos Rastislav , Schenz Judith , Uhle Florian , Weigand Markus A. , Frank Maurice , Kahraman Mustafa , Heuvelman Marco , Sikosek Tobias , Rajakumar Timothy , Gerwing Jennifer , Skottke Jasmin , Daniel-Moreno Alberto , Rudolf Christina , Hinkfoth Franziska , Tikk Kaja , Christopoulos Petros , Klotz Laura V. , Winter Hauke , Kreuter Michael , Steinkraus Bruno R. 
Published: February 2024

AbstractmiR-Blood is a high-quality, small RNA expression atlas for the major components of human peripheral blood (plasma, erythrocytes, thrombocytes, monocytes, neutrophils, eosinophils, basophils, natural killer cells, CD4+ T cells, CD8+ T cells, and B cells). Based on the purified blood components from 52 individuals, the dataset provides a comprehensive repository for the expression of 4971 small RNAs from eight non-coding RNA classes.
Escherichia coli resistance mechanism AcrAB-TolC efflux pump interactions with commonly used antibiotics: a molecular dynamics study
Authors: Smith Brooke L. , Fernando Sandun , King Maria D. 
Published: February 2024

AbstractWhile antibiotic resistance poses a threat from both Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), GNB pose a more imminent public health hazard globally. GNB are a threat to growing antibiotic resistance because of the complex makeup of the membrane. The AcrAB-TolC efflux pump is a known resistance mechanism of Escherichia coli (E. coli) cells. This study utilized molecular dynamics modeling to visualize some of the changes occurring at a molecular level when airborne bacteria are exposed to stress and antibiotics. This study was conducted to build upon previous experimental research showing that there is an increase in antibiotic resistance and efflux pump activity when exposed to aerosolization. AcrB and AcrAB-TolC proteins were simulated under standard and increased pressure to compare the effect of aerosolization on the binding to the three different antibiotics (puromycin (PUY), ampicillin (AMP) and sulfamethoxazole-trimethoprim (SXT)) to the AcrB binding site. Analysis such as root-mean-square deviation of atomic positions and root-mean-square fluctuation, the opening of TolC, and the significant molecular mechanics with generalized Born and surface area solvation (MM-GBSA) scores associated with specific ligands were recorded. Resistance in experimental data indicated a relationship between the docking scores and some ligand–protein interactions. Results showed that there was more flexibility in the proteins within simulations conducted under standard pressure for the AcrB protein and the full tripartite complex AcrAB-TolC, showing that increased pressure causes more rigidity. MM-GBSA scores, used to calculate the free energy of ligand–protein binding, did not show a significant change, but interestingly, the strongest MM-GBSA scores were for ligands that moved to another binding pocket and did not result in resistance or opening of the efflux pump. However, the ligand moved from the binding site and did not cause the opening of TolC to increase significantly, whereas PUY and AMP were bound to the binding site for the duration of all simulations. AMP ligands under increased pressure showed the largest change in opening of the TolC efflux pump and aligns with experimental data showing E. coli cells had the most resistance to AMP after aerosolization. These results, in addition to other real-time changes such as OM proteins and mutations of targets within the cell, could be used to delineate and mitigate antibiotic resistance mechanisms.
Characterization of antibiotic resistance genes and mobile genetic elements in Escherichia coli isolated from captive black bears
Authors: Liu Hang , Shi Keyun , Wang Yuhan , Zhong Wenhao , Pan Shulei , Zhou Lei , Cheng Yuehong , Yuan Yu , Zhou Ziyao , Liu Haifeng , Zhang Shaqiu , Peng Guangneng , Yan Qigui , Luo Yan , Zhang Xiaoli , Zhong Zhijun 
Published: February 2024

AbstractThe objective of this study was to analyze the antimicrobial resistance (AMR) characteristics produced by antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and gene cassettes in Escherichia coli isolated from the feces of captive black bears. Antimicrobial susceptibility testing was performed by using the disk diffusion method, and both MGEs and integron gene cassettes were detected by polymerase chain reaction. Our results showed that 43.7% (62/142) of the isolates were multidrug resistant strains and 97.9% (139/142) of the isolates were resistant to at least one antibiotic. The highest AMR phenotype was observed for tetracycline (79.6%, 113/142), followed by ampicillin (50.0%, 71/142), trimethoprim-sulfamethoxazole (43.7%, 62/142) and cefotaxime (35.9%, 51/142). However, all isolates were susceptible to tobramycin. tetA had the highest occurrence in 6 ARGs in 142 E. coli isolates (76.8%, 109/142). Ten mobile genetic elements were observed and IS26 was dominant (88.0%, 125/142). ISECP1 was positively associated with five β-lactam antibiotics. ISCR3/14, IS1133 and intI3 were not detected. Seventy-five E. coli isolates (65 intI1-positive isolates, 2 intI2-positive isolates and 8 intI1 + intI2-positive isolates) carried integrons. Five gene cassettes (dfrA1, aadA2, dfrA17-aadA5, aadA2-dfrA12 and dfrA1-aadA1) were identified in the intI1-positive isolates and 2 gene cassettes (dfrA1-catB2-sat2-aadA1 and dfrA1-catB2-sat1-aadA1) were observed in the intI2-positive isolates. Monitoring of ARGs, MGEs and gene cassettes is important to understand the prevalence of AMR, which may help to introduce measures to prevent and control of AMR in E. coli for captive black bears.
A digital image colorimetry system based on smart devices for immediate and simultaneous determination of enzyme-linked immunosorbent assays
Authors: Mirhosseini Shaghayegh , Nasiri Aryanaz Faghih , Khatami Fatemeh , Mirzaei Akram , Aghamir Seyed Mohammad Kazem , Kolahdouz Mohammadreza 
Published: January 2024

AbstractStandard enzyme-linked immunosorbent assays based on microplates are frequently utilized for various molecular sensing, disease screening, and nanomedicine applications. Comparing this multi-well plate batched analysis to non-batched or non-standard testing, the diagnosis expenses per patient are drastically reduced. However, the requirement for rather big and pricey readout instruments prevents their application in environments with limited resources, especially in the field. In this work, a handheld cellphone-based colorimetric microplate reader for quick, credible, and novel analysis of digital images of human cancer cell lines at a reasonable price was developed. Using our in-house-developed app, images of the plates are captured and sent to our servers, where they are processed using a machine learning algorithm to produce diagnostic results. Using FDA-approved human epididymis protein of ovary IgG (HE4), prostate cancer cell line (PC3), and bladder cancer cell line (5637) ELISA tests, we successfully examined this mobile platform. The accuracies for the HE4, PC3, and 5637 tests were 93%, 97.5%, and 97.2%, respectively. By contrasting the findings with the measurements made using optical absorption EPOCH microplate readers and optical absorption Tecan microplate readers, this approach was found to be accurate and effective. As a result, digital image colorimetry on smart devices offered a practical, user-friendly, affordable, precise, and effective method for quickly identifying human cancer cell lines. Thus, healthcare providers might use this portable device to carry out high-throughput illness screening, epidemiological investigations or monitor vaccination campaigns.
Knockdown of Hyaluronan synthase 2 suppresses liver fibrosis in mice via induction of transcriptomic changes similar to 4MU treatment
Authors: Halimani Noreen , Nesterchuk Mikhail , Tsitrina Alexandra A. , Sabirov Marat , Andreichenko Irina N. , Dashenkova Nataliya O. , Petrova Elizaveta , Kulikov Alexey M. , Zatsepin Timofei S. , Romanov Roman A. , Mikaelyan Arsen S. , Kotelevtsev Yuri V. 
Published: February 2024

AbstractHepatic fibrosis remains a significant clinical challenge due to ineffective treatments. 4-methylumbelliferone (4MU), a hyaluronic acid (HA) synthesis inhibitor, has proven safe in phase one clinical trials. In this study, we aimed to ameliorate liver fibrosis by inhibiting HA synthesis. We compared two groups of mice with CCl4-induced fibrosis, treated with 4-methylumbelliferone (4MU) and hyaluronan synthase 2 (HAS2) targeting siRNA (siHAS2). The administration of 4MU and siHAS2 significantly reduced collagen and HA deposition, as well as biochemical markers of hepatic damage induced by repeated CCl4 injections. The transcriptomic analysis revealed converging pathways associated with downstream HA signalling. 4MU- and siHAS2-treated fibrotic livers shared 405 upregulated and 628 downregulated genes. These genes were associated with xenobiotic and cholesterol metabolism, mitosis, endoplasmic reticulum stress, RNA processing, and myeloid cell migration. The functional annotation of differentially expressed genes (DEGs) in siHAS2-treated mice revealed attenuation of extracellular matrix-associated pathways. In comparison, in the 4MU-treated group, DEGs were related to lipid and bile metabolism pathways and cell cycle. These findings confirm that HAS2 is an important pharmacological target for suppressing hepatic fibrosis using siRNA.
Blood transcriptomics analysis offers insights into variant-specific immune response to SARS-CoV-2
Authors: Hoffmann Markus , Willruth Lina-Liv , Dietrich Alexander , Lee Hye Kyung , Knabl Ludwig , Trummer Nico , Baumbach Jan , Furth Priscilla A. , Hennighausen Lothar , List Markus 
Published: February 2024

AbstractBulk RNA sequencing (RNA-seq) of blood is typically used for gene expression analysis in biomedical research but is still rarely used in clinical practice. In this study, we propose that RNA-seq should be considered a diagnostic tool, as it offers not only insights into aberrant gene expression and splicing but also delivers additional readouts on immune cell type composition as well as B-cell and T-cell receptor (BCR/TCR) repertoires. We demonstrate that RNA-seq offers insights into a patient’s immune status via integrative analysis of RNA-seq data from patients infected with various SARS-CoV-2 variants (in total 196 samples with up to 200 million reads sequencing depth). We compare the results of computational cell-type deconvolution methods (e.g., MCP-counter, xCell, EPIC, quanTIseq) to complete blood count data, the current gold standard in clinical practice. We observe varying levels of lymphocyte depletion and significant differences in neutrophil levels between SARS-CoV-2 variants. Additionally, we identify B and T cell receptor (BCR/TCR) sequences using the tools MiXCR and TRUST4 to show that—combined with sequence alignments and BLASTp—they could be used to classify a patient's disease. Finally, we investigated the sequencing depth required for such analyses and concluded that 10 million reads per sample is sufficient. In conclusion, our study reveals that computational cell-type deconvolution and BCR/TCR methods using bulk RNA-seq analyses can supplement missing CBC data and offer insights into immune responses, disease severity, and pathogen-specific immunity, all achievable with a sequencing depth of 10 million reads per sample.
A novel exosome based therapeutic intervention against neuroendocrine prostate cancer
Authors: Saini Sharanjot , Sreekumar Amritha , Nathani Sandip , Asante Diana M. , Simmons Matthew N. 
Published: February 2024

AbstractNeuroendocrine prostate cancer (NEPC) is a highly lethal variant of castration-resistant prostate cancer (CRPC) with poor survival rates. Current treatment options for NEPC are limited to highly toxic platinum drugs highlighting the urgent need for new therapies. This study aimed to develop a novel therapeutic approach using engineered exosomes against NEPC. Exosomes were modified to target CEACAM5, an NEPC surface antigen, by attaching CEACAM5 antibodies to HEK293T exosomes. These exosomes were loaded with drugs inhibiting EZH2 and the androgen receptor (AR) as recent research shows a persistent role of AR in NEPC wherein it plays a concerted role with EZH2 in driving neuronal gene programs. In vitro experiments with NEPC cell lines demonstrated that CEACAM5-targeted exosomes were specifically taken up by NEPC cells, leading to reduced cellular viability and decreased expression of neuronal markers. Further in vivo tests using a NEPC patient-derived xenograft model (LuCaP145.1) showed significant tumor regression in mice treated with engineered exosomes compared to control mice receiving IgG-labeled exosomes. These results suggest that CEACAM5-engineered exosomes hold promise as a targeted therapy for NEPC. Importantly, our exosome engineering strategy is versatile and can be adapted to target various surface antigens in prostate cancer and other diseases.