bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crosstalk between CRISPR-Cas9 and the human transcriptome
Authors: Smargon Aaron A. , Madrigal Assael A. , Yee Brian A. , Dong Kevin D. , Mueller Jasmine R. , Yeo Gene W. 
Published: March 2022

AbstractCRISPR-Cas9 expression independent of its cognate synthetic guide RNA (gRNA) causes widespread genomic DNA damage in human cells. To investigate whether Cas9 can interact with endogenous human RNA transcripts independent of its guide, we perform eCLIP (enhanced CLIP) of Cas9 in human cells and find that Cas9 reproducibly interacts with hundreds of endogenous human RNA transcripts. This association can be partially explained by a model built on gRNA secondary structure and sequence. Critically, transcriptome-wide Cas9 binding sites do not appear to correlate with published genome-wide Cas9 DNA binding or cut-site loci under gRNA co-expression. However, even under gRNA co-expression low-affinity Cas9-human RNA interactions (which we term CRISPR crosstalk) do correlate with published elevated transcriptome-wide RNA editing. Our findings do not support the hypothesis that human RNAs can broadly guide Cas9 to bind and cleave human genomic DNA, but they illustrate a cellular and RNA impact likely inherent to CRISPR-Cas systems.
Splicing the active phases of copper/cobalt-based catalysts achieves high-rate tandem electroreduction of nitrate to ammonia
Authors: He Wenhui , Zhang Jian , Dieckhöfer Stefan , Varhade Swapnil , Brix Ann Cathrin , Lielpetere Anna , Seisel Sabine , Junqueira João R. C. , Schuhmann Wolfgang 
Published: March 2022

AbstractElectrocatalytic recycling of waste nitrate (NO3−) to valuable ammonia (NH3) at ambient conditions is a green and appealing alternative to the Haber−Bosch process. However, the reaction requires multi-step electron and proton transfer, making it a grand challenge to drive high-rate NH3 synthesis in an energy-efficient way. Herein, we present a design concept of tandem catalysts, which involves coupling intermediate phases of different transition metals, existing at low applied overpotentials, as cooperative active sites that enable cascade NO3−-to-NH3 conversion, in turn avoiding the generally encountered scaling relations. We implement the concept by electrochemical transformation of Cu−Co binary sulfides into potential-dependent core−shell Cu/CuOx and Co/CoO phases. Electrochemical evaluation, kinetic studies, and in−situ Raman spectra reveal that the inner Cu/CuOx phases preferentially catalyze NO3− reduction to NO2−, which is rapidly reduced to NH3 at the nearby Co/CoO shell. This unique tandem catalyst system leads to a NO3−-to-NH3 Faradaic efficiency of 93.3 ± 2.1% in a wide range of NO3− concentrations at pH 13, a high NH3 yield rate of 1.17 mmol cm−2 h−1 in 0.1 M NO3− at −0.175 V vs. RHE, and a half-cell energy efficiency of ~36%, surpassing most previous reports.
Two zinc finger proteins with functions in m6A writing interact with HAKAI
Authors: Zhang Mi , Bodi Zsuzsanna , Mackinnon Katarzyna , Zhong Silin , Archer Nathan , Mongan Nigel P. , Simpson Gordon G. , Fray Rupert G. 
Published: March 2022

AbstractThe methyltransferase complex (m6A writer), which catalyzes the deposition of N6-methyladenosine (m6A) in mRNAs, is highly conserved across most eukaryotic organisms, but its components and interactions between them are still far from fully understood. Here, using in vivo interaction proteomics, two HAKAI-interacting zinc finger proteins, HIZ1 and HIZ2, are discovered as components of the Arabidopsis m6A writer complex. HAKAI is required for the interaction between HIZ1 and MTA (mRNA adenosine methylase A). Whilst HIZ1 knockout plants have normal levels of m6A, plants in which it is overexpressed show reduced methylation and decreased lateral root formation. Mutant plants lacking HIZ2 are viable but have an 85% reduction in m6A abundance and show severe developmental defects. Our findings suggest that HIZ2 is likely the plant equivalent of ZC3H13 (Flacc) of the metazoan m6A-METTL Associated Complex.
Ultralong phosphorescence cellulose with excellent anti-bacterial, water-resistant and ease-to-process performance
Authors: Zhang Xin , Cheng Yaohui , You Jingxuan , Zhang Jinming , Yin Chunchun , Zhang Jun 
Published: March 2022

AbstractHerein, we present a phosphorescent cationized cellulose derivative by simply introducing ionic structures, including cyanomethylimidazolium cations and chloride anions, into cellulose chains. The imidazolium cations with the cyano group and nitrogen element promote intersystem crossing. The cyano-containing cations, chloride anions and hydroxyl groups of cellulose form multiple hydrogen bonding interactions and electrostatic attraction interactions, effectively inhibiting the non-radiative transitions. The resultant cellulose-based RTP material is easily processed into phosphorescent films, fibers, coatings and patterns by using eco-friendly aqueous solution processing strategies. Furthermore, after we construct a cross-linking structure by adding a small amount of glutaraldehyde as the cross-linking agent, the as-fabricated phosphorescent patterns exhibit excellent antibacterial properties and water resistance. Therefore, considering the outstanding biodegradability and sustainability of cellulose materials, cellulose-based easy-to-process RTP materials can act as antibacterial, water-resistant, and eco-friendly phosphorescent patterns, coatings and bulk materials, which have enormous potential in advanced anti-counterfeiting, information encryption, disposable smart labels, etc.
Phase separation on cell surface facilitates bFGF signal transduction with heparan sulphate
Authors: Xue Song , Zhou Fan , Zhao Tian , Zhao Huimin , Wang Xuewei , Chen Long , Li Jin-ping , Luo Shi-Zhong 
Published: March 2022

AbstractLiquid-liquid phase separation (LLPS) plays important roles in various cellular processes, facilitating membrane-less organelles construction, chromatin condensation, signal transduction on inner membrane and many other processes. Current perception is that LLPS relies on weak multivalent interactions and crowded environments intracellularly. In this study, we demonstrate that heparan sulfate can serve as a platform to induce the phase separation of basic fibroblast growth factor on cell surface. The phase separation model provides an alternative mechanism how bFGF is enriched to its receptors, therefore triggering the signaling transduction. The research provides insights on the mechanism how growth factors can be recruited to cell surface by heparan sulfate and execute their functions, extending people’s view on phase separation from intracellular to extracellular proteins at cellular level.
Effects of high fructose corn syrup on intestinal microbiota structure and obesity in mice
Authors: Wang Xiaorong , Zhu Liying , Li Xiaoqiong , Wang Xin , Hao Ruirong , Li Jinjun 
Published: March 2022

AbstractHigh fructose corn syrup (HFCS)-associated health problems have raised concerns. We investigated the effects of HFCS-containing drinking water on body fat, intestinal microbiota structure of mice, and the relationships between them. HFCS drinking water significantly increased body fat content and altered the intestinal microbiome. The Christensenellaceae R-7 group negatively correlated with body weight, perirenal fat, epididymal fat, and liver fat percentage.
Pandemic-response adenoviral vector and RNA vaccine manufacturing
Authors: Kis Zoltán , Tak Kyungjae , Ibrahim Dauda , Papathanasiou Maria M. , Chachuat Benoît , Shah Nilay , Kontoravdi Cleo 
Published: March 2022

AbstractRapid global COVID-19 pandemic response by mass vaccination is currently limited by the rate of vaccine manufacturing. This study presents a techno-economic feasibility assessment and comparison of three vaccine production platform technologies deployed during the COVID-19 pandemic: (1) adenovirus-vectored (AVV) vaccines, (2) messenger RNA (mRNA) vaccines, and (3) the newer self-amplifying RNA (saRNA) vaccines. Besides assessing the baseline performance of the production process, impact of key design and operational uncertainties on the productivity and cost performance of these vaccine platforms is quantified using variance-based global sensitivity analysis. Cost and resource requirement projections are computed for manufacturing multi-billion vaccine doses for covering the current global demand shortage and for providing annual booster immunisations. The model-based assessment provides key insights to policymakers and vaccine manufacturers for risk analysis, asset utilisation, directions for future technology improvements and future epidemic/pandemic preparedness, given the disease-agnostic nature of these vaccine production platforms.
Centrin-deficient Leishmania mexicana confers protection against New World cutaneous leishmaniasis
Authors: Volpedo Greta , Pacheco-Fernandez Thalia , Holcomb Erin A. , Zhang Wen-Wei , Lypaczewski Patrick , Cox Blake , Fultz Rebecca , Mishan Chelsea , Verma Chaitenya , Huston Ryan H. , Wharton Abigail R. , Dey Ranadhir , Karmakar Subir , Oghumu Steve , Hamano Shinjiro , Gannavaram Sreenivas , Nakhasi Hira L. , Matlashewski Greg , Satoskar Abhay R. 
Published: March 2022

AbstractLeishmaniasis is a neglected protozoan disease affecting over 12 million people globally with no approved vaccines for human use. New World cutaneous leishmaniasis (CL) caused by L. mexicana is characterized by the development of chronic non-healing skin lesions. Using the CRISPR/Cas9 technique, we have generated live attenuated centrin knockout L. mexicana (LmexCen−/−) parasites. Centrin is a cytoskeletal protein important for cellular division in eukaryotes and, in Leishmania, is required only for intracellular amastigote replication. We have investigated the safety and immunogenicity characteristics of LmexCen−/− parasites by evaluating their survival and the cytokine production in bone-marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs) in vitro. Our data shows that LmexCen−/− amastigotes present a growth defect, which results in significantly lower parasitic burdens and increased protective cytokine production in infected BMDMs and BMDCs, compared to the wild type (WT) parasites. We have also determined the safety and efficacy of LmexCen−/− in vivo using experimental murine models of L. mexicana. We demonstrate that LmexCen−/− parasites are safe and do not cause lesions in susceptible mouse models. Immunization with LmexCen−/− is also efficacious against challenge with WT L. mexicana parasites in genetically different BALB/c and C57BL/6 mouse models. Vaccinated mice did not develop cutaneous lesions, displayed protective immunity, and showed significantly lower parasitic burdens at the infection site and draining lymph nodes compared to the control group. Overall, we demonstrate that LmexCen−/− parasites are safe and efficacious against New World cutaneous leishmaniasis in pre-clinical models.
Label-free metabolic and structural profiling of dynamic biological samples using multimodal optical microscopy with sensorless adaptive optics
Authors: Iyer Rishyashring R. , Sorrells Janet E. , Yang Lingxiao , Chaney Eric J. , Spillman Darold R. , Tibble Brian E. , Renteria Carlos A. , Tu Haohua , Žurauskas Mantas , Marjanovic Marina , Boppart Stephen A. 
Published: March 2022

AbstractLabel-free optical microscopy has matured as a noninvasive tool for biological imaging; yet, it is criticized for its lack of specificity, slow acquisition and processing times, and weak and noisy optical signals that lead to inaccuracies in quantification. We introduce FOCALS (Fast Optical Coherence, Autofluorescence Lifetime imaging, and Second harmonic generation) microscopy capable of generating NAD(P)H fluorescence lifetime, second harmonic generation (SHG), and polarization-sensitive optical coherence microscopy (OCM) images simultaneously. Multimodal imaging generates quantitative metabolic and morphological profiles of biological samples in vitro, ex vivo, and in vivo. Fast analog detection of fluorescence lifetime and real-time processing on a graphical processing unit enables longitudinal imaging of biological dynamics. We detail the effect of optical aberrations on the accuracy of FLIM beyond the context of undistorting image features. To compensate for the sample-induced aberrations, we implemented a closed-loop single-shot sensorless adaptive optics solution, which uses computational adaptive optics of OCM for wavefront estimation within 2 s and improves the quality of quantitative fluorescence imaging in thick tissues. Multimodal imaging with complementary contrasts improves the specificity and enables multidimensional quantification of the optical signatures in vitro, ex vivo, and in vivo, fast acquisition and real-time processing improve imaging speed by 4–40 × while maintaining enough signal for quantitative nonlinear microscopy, and adaptive optics improves the overall versatility, which enable FOCALS microscopy to overcome the limits of traditional label-free imaging techniques.
Quantifying traffic noise pollution levels: a cross-sectional survey in South Africa
Authors: Moroe Nomfundo , Mabaso Paballo 
Published: March 2022

AbstractDespite the alarming increase in environmental noise pollution, particularly road traffic noise, in developing countries, there seems to be no awareness regarding the long-term impacts of noise, specifically traffic noise, on the health outcomes of individuals exposed to excessive noise. Additionally, there is a dearth of studies on noise and its effects utilising the pollution modelling technique known as Pollution Standard Index (PSI) to analyse the impact of noise pollution on exposed individuals. The aim of this study was to investigate the noise levels commuters are exposed to and to apply PSI to determine the level of exposure. We conducted a cross-sectional study at two taxi ranks, over 28 days. Eighty-four noise measurements were collected using a sound level meter and a dosimeter at different times of the day and month, peak vs off-peak hours and busy days vs quiet days. Data were collected between April and July 2019. We used the Pollution Standard Index to analyse the data. Noise levels were above the permissible commercial noise levels as they fell within the extremely dangerous noise sensitivity zone as determined by the PSI. Furthermore, the noise levels fell below the WHO maximum permissible level of 90 dB. There was no statistical difference between the means of the open and closed ranks. Dosimeter noise level recordings fell within the satisfactory zone as measurements were below 300 PSI, which is considered unhealthy. There is a need to raise awareness on the dangers and effects of noise pollution in developing countries, as their populations are exposed to road traffic noise.
Salivary S100 calcium-binding protein beta (S100B) and neurofilament light (NfL) after acute exposure to repeated head impacts in collegiate water polo players
Authors: Monroe Derek C. , Thomas Elizabeth A. , Cecchi Nicholas J. , Granger Douglas A. , Hicks James W. , Small Steven L. 
Published: March 2022

AbstractBlood-based biomarkers of brain injury may be useful for monitoring brain health in athletes at risk for concussions. Two putative biomarkers of sport-related concussion, neurofilament light (NfL), an axonal structural protein, and S100 calcium-binding protein beta (S100B), an astrocyte-derived protein, were measured in saliva, a biofluid which can be sampled in an athletic setting without the risks and burdens associated with blood sampled by venipuncture. Samples were collected from men’s and women’s collegiate water polo players (n = 65) before and after a competitive tournament. Head impacts were measured using sensors previously evaluated for use in water polo, and video recordings were independently reviewed for the purpose of validating impacts recorded by the sensors. Athletes sustained a total of 107 head impacts, all of which were asymptomatic (i.e., no athlete was diagnosed with a concussion or more serious). Post-tournament salivary NfL was directly associated with head impact frequency (RR = 1.151, p = 0.025) and cumulative head impact magnitude (RR = 1.008, p = 0.014), while controlling for baseline salivary NfL. Change in S100B was not associated with head impact exposure (RR < 1.001, p > 0.483). These patterns suggest that repeated head impacts may cause axonal injury, even in asymptomatic athletes.
Portable SA/CMC entrapped bimetallic magnetic fly ash zeolite spheres for heavy metals contaminated industrial effluents treatment via batch and column studies
Authors: Angaru Ganesh Kumar Reddy , Choi Yu-Lim , Lingamdinne Lakshmi Prasanna , Koduru Janardhan Reddy , Yang Jae-Kyu , Chang Yoon-Young , Karri Rama Rao 
Published: March 2022

AbstractHeavy metals are perceived as a significant environmental concern because of their toxic effect, bioaccumulation, and persistence. In this work, a novel sodium alginate (SA) and carboxymethylcellulose (CMC) entrapped with fly ash derived zeolite stabilized nano zero-valent iron and nickel (ZFN) (SA/CMC-ZFN), followed by crosslinking with CaCl2, is synthesized and applied for remediation of Cu(II) and Cr(VI) from industrial effluent. The characterization of the adsorbent and its surface mechanism for removing metals were investigated using advanced instrumental techniques, including XRD, FT-IR, SEM–EDX, BET, and XPS. The outcomes from the batch experiments indicated that monolayer adsorption on homogeneous surfaces (Langmuir isotherm model) was the rate-limiting step in both heavy metals sorption processes. The maximum adsorption capacity of as-prepared SA/CMC-ZFN was 63.29 and 10.15 mg/g for Cu(II) and Cr(VI), respectively. Owing to the fact that the wastewater released from industries are large and continuous, a continuous column is installed for simultaneous removal of heavy metal ions from real industrial wastewater. The outcomes revealed the potential of SA/CMC-ZFN as an efficient adsorbent. The experimental breakthrough curves fitted well with the theoretical values of Thomas and Yoon-Nelson models. Overall, the results indicated that SA/CMC-ZFN is a viable, efficient, and cost-effective water treatment both interms of batch and column processes.
Identification of a novel immune-related long noncoding RNA signature to predict the prognosis of bladder cancer
Authors: Ren Wenjing , Zuo Siyu , Yang Liang , Tu Renyuan , Wang Ping , Zhang Xiling 
Published: March 2022

AbstractTumour immune regulation has attracted widespread attention, and long noncoding RNAs (lncRNAs) play an important role in this process. Therefore, we evaluated patient prognosis by exploring the relationship between bladder cancer (BLCA) and immune-related lncRNAs (IRlncRNAs). Transcriptome data and immune-related genes were analysed for coexpression, and then, the IRlncRNAs were analysed to determine the differentially expressed IRlncRNAs (DEIRlncRNAs) between normal and tumour samples in The Cancer Genome Atlas. The screened lncRNAs were pairwise paired and combined with clinical data, and finally, a signature was constructed by Lasso regression and Cox regression in 13 pairs of DEIRlncRNAs. According to the Akaike information criterion (AIC) values of the 1-year receiver operating characteristic curve, BLCA patients were stratified into high- or low-risk groups. The high-risk group had a worse prognosis. A comprehensive analysis showed that differences in risk scores were associated with the immune status of BLCA-infiltrated patients. The identified signature was correlated with the expression of immune checkpoint inhibitor-related molecules and sensitivity to chemotherapeutic drugs. We also identified three BLCA clusters with different immune statuses and prognoses that are also associated with immunotherapy response and drug sensitivity. In conclusion, we constructed a powerful predictive signature with high accuracy and validated its prognostic value.
Evaluation of phototoxicity induced by the anticancer drug rucaparib
Authors: Mateos-Pujante Alejandro , Jiménez María Consuelo , Andreu Inmaculada 
Published: March 2022

AbstractRucaparib (RCP) is a potent selective inhibitor of both PARP-1 and PARP-2 enzymes that induces synthetic lethality in cancer cells. It is used for the treatment of breast and ovarian tumors harboring deleterious germline or somatic cancer susceptibility genes mutations. Although RCP has an indole chromophore in its structure, it displays a bathochromic shift of the absorption band towards the UVA region of sunlight, thus extending the active fraction of solar light able to produce photosensitivity reactions. In this context, it is highly interesting to study the photo(geno)toxicity disorders associated with this drug, bearing in mind that, for dermatologists it is crucial to understand the toxicity mechanism to improve clinical management. In the present work, RCP has shown to be potentially phototoxic, as observed in the neutral red uptake phototoxicity test. Moreover, this significant phototoxicity is attributed to both proteins and genomic DNA, as revealed in the protein photooxidation and comet assays. The results obtained are highly relevant concerning RCP photosafety and become clinically important in the context of identification of the cutaneous adverse events that can be associated with the targeted therapies. Interestingly, this is the first example of a PARP inhibitor able to induce photosensitized damage to biomolecules.
Statistical distortion of supervised learning predictions in optical microscopy induced by image compression
Authors: Pomarico Enrico , Schmidt Cédric , Chays Florian , Nguyen David , Planchette Arielle , Tissot Audrey , Roux Adrien , Pagès Stéphane , Batti Laura , Clausen Christoph , Lasser Theo , Radenovic Aleksandra , Sanguinetti Bruno , Extermann Jérôme 
Published: March 2022

AbstractThe growth of data throughput in optical microscopy has triggered the extensive use of supervised learning (SL) models on compressed datasets for automated analysis. Investigating the effects of image compression on SL predictions is therefore pivotal to assess their reliability, especially for clinical use. We quantify the statistical distortions induced by compression through the comparison of predictions on compressed data to the raw predictive uncertainty, numerically estimated from the raw noise statistics measured via sensor calibration. Predictions on cell segmentation parameters are altered by up to 15% and more than 10 standard deviations after 16-to-8 bits pixel depth reduction and 10:1 JPEG compression. JPEG formats with higher compression ratios show significantly larger distortions. Interestingly, a recent metrologically accurate algorithm, offering up to 10:1 compression ratio, provides a prediction spread equivalent to that stemming from raw noise. The method described here allows to set a lower bound to the predictive uncertainty of a SL task and can be generalized to determine the statistical distortions originated from a variety of processing pipelines in AI-assisted fields.