bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYCN induces cell-specific tumorigenic growth in RB1-proficient human retinal organoid and chicken retina models of retinoblastoma
Authors: Blixt Maria K. E. , Hellsand Minas , Konjusha Dardan , Zhang Hanzhao , Stenfelt Sonya , Åkesson Mikael , Rafati Nima , Tararuk Tatsiana , Stålhammar Gustav , All-Eriksson Charlotta , Ring Henrik , Hallböök Finn 
Published: June 2022

AbstractRetinoblastoma is a rare, intraocular paediatric cancer that originates in the neural retina and is most frequently caused by bi-allelic loss of RB1 gene function. Other oncogenic mutations, such as amplification and increased expression of the MYCN gene, have been found even with proficient RB1 function. In this study, we investigated whether MYCN over-expression can drive carcinogenesis independently of RB1 loss-of-function mutations. The aim was to elucidate the events that result in carcinogenesis and identify the cancer cell-of-origin. We used the chicken retina, a well-established model for studying retinal neurogenesis, and established human embryonic stem cell-derived retinal organoids as model systems. We over-expressed MYCN by electroporation of piggyBac genome-integrating expression vectors. We found that over-expression of MYCN induced tumorigenic growth with high frequency in RB1-proficient chicken retinas and human organoids. In both systems, the tumorigenic cells expressed markers for undifferentiated cone photoreceptor/horizontal cell progenitors. The over-expression resulted in metastatic retinoblastoma within 7–9 weeks in chicken. Cells expressing MYCN could be grown in vitro and, when orthotopically injected, formed tumours that infiltrated the sclera and optic nerve and expressed markers for cone progenitors. Investigation of the tumour cell phenotype determined that the potential for neoplastic growth was embryonic stage-dependent and featured a cell-specific resistance to apoptosis in the cone/horizontal cell lineage, but not in ganglion or amacrine cells. We conclude that MYCN over-expression is sufficient to drive tumorigenesis and that a cell-specific resistance to apoptosis in the cone/horizontal cell lineage mediates the cancer phenotype.
Dnah9 mutant mice and organoid models recapitulate the clinical features of patients with PCD and provide an excellent platform for drug screening
Authors: Zheng Rui , Yang Wenhao , Wen Yuting , Xie Liang , Shi Fang , Lu Danli , Luo Jiaxin , Li Yan , Zhang Rui , Chen Ting , Chen Lina , Xu Wenming , Liu Hanmin 
Published: June 2022

AbstractPrimary cilia dyskinesia (PCD) is a rare genetic disease caused by ciliary structural or functional defects. It causes severe outcomes in patients, including recurrent upper and lower airway infections, progressive lung failure, and randomization of heterotaxy. To date, although 50 genes have been shown to be responsible for PCD, the etiology remains elusive. Meanwhile, owing to the lack of a model mimicking the pathogenesis that can be used as a drug screening platform, thereby slowing the development of related therapies. In the current study, we identified compound mutation of DNAH9 in a patient with PCD with the following clinical features: recurrent respiratory tract infections, low lung function, and ultrastructural defects of the outer dynein arms (ODAs). Bioinformatic analysis, structure simulation assay, and western blot analysis showed that the mutations affected the structure and expression of DNAH9 protein. Dnah9 knock-down (KD) mice recapitulated the patient phenotypes, including low lung function, mucin accumulation, and increased immune cell infiltration. Immunostaining, western blot, and co-immunoprecipitation analyses were performed to clarify that DNAH9 interacted with CCDC114/GAS8 and diminished their protein levels. Furthermore, we constructed an airway organoid of Dnah9 KD mice and discovered that it could mimic the key features of the PCD phenotypes. We then used organoid as a drug screening model to identify mitochondrial-targeting drugs that can partially elevate cilia beating in Dnah9 KD organoid. Collectively, our results demonstrated that Dnah9 KD mice and an organoid model can recapture the clinical features of patients with PCD and provide an excellent drug screening platform for human ciliopathies.
A multi-ethnic polygenic risk score is associated with hypertension prevalence and progression throughout adulthood
Authors: Kurniansyah Nuzulul , Goodman Matthew O. , Kelly Tanika N. , Elfassy Tali , Wiggins Kerri L. , Bis Joshua C. , Guo Xiuqing , Palmas Walter , Taylor Kent D. , Lin Henry J. , Haessler Jeffrey , Gao Yan , Shimbo Daichi , Smith Jennifer A. , Yu Bing , Feofanova Elena V. , Smit Roelof A. J. , Wang Zhe , Hwang Shih-Jen , Liu Simin , Wassertheil-Smoller Sylvia , Manson JoAnn E. , Lloyd-Jones Donald M. , Rich Stephen S. , Loos Ruth J. F. , Redline Susan , Correa Adolfo , Kooperberg Charles , Fornage Myriam , Kaplan Robert C. , Psaty Bruce M. , Rotter Jerome I. , Arnett Donna K. , Morrison Alanna C. , Franceschini Nora , Levy Daniel ,   the NHLBI Trans-Omics in Precision Medicine (TOPMed) Consortium, Bis Joshua C. , Guo Xiuqing , Taylor Kent D. , Lin Henry J. , Haessler Jeffrey , Gao Yan , Smith Jennifer A. , Liu Simin , Wassertheil-Smoller Sylvia , Manson JoAnn E. , Rich Stephen S. , Redline Susan , Correa Adolfo , Kooperberg Charles , Fornage Myriam , Kaplan Robert C. , Psaty Bruce M. , Rotter Jerome I. , Arnett Donna K. , Franceschini Nora , Levy Daniel , Sofer Tamar , Sofer Tamar 
Published: June 2022

AbstractIn a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is trained using genome-wide association studies (GWAS) for systolic, diastolic blood pressure, and hypertension, respectively. For each trait, PRS is selected by optimizing the coefficient of variation (CV) across estimated effect sizes from multiple potential PRS using the same GWAS, after which the 3 trait-specific PRSs are combined via an unweighted sum called “PRSsum”, forming the HTN-PRS. The HTN-PRS is associated with both prevalent and incident hypertension at 4-6 years of follow up. This association is further confirmed in age-stratified analysis. In an independent biobank of 40,201 individuals, the HTN-PRS is confirmed to be predictive of increased risk for coronary artery disease, ischemic stroke, type 2 diabetes, and chronic kidney disease.
The antenna of far-red absorbing cyanobacteria increases both absorption and quantum efficiency of Photosystem II
Authors: Mascoli Vincenzo , Bhatti Ahmad Farhan , Bersanini Luca , van Amerongen Herbert , Croce Roberta 
Published: June 2022

AbstractCyanobacteria carry out photosynthetic light-energy conversion using phycobiliproteins for light harvesting and the chlorophyll-rich photosystems for photochemistry. While most cyanobacteria only absorb visible photons, some of them can acclimate to harvest far-red light (FRL, 700–800 nm) by integrating chlorophyll f and d in their photosystems and producing red-shifted allophycocyanin. Chlorophyll f insertion enables the photosystems to use FRL but slows down charge separation, reducing photosynthetic efficiency. Here we demonstrate with time-resolved fluorescence spectroscopy that on average charge separation in chlorophyll-f-containing Photosystem II becomes faster in the presence of red-shifted allophycocyanin antennas. This is different from all known photosynthetic systems, where additional light-harvesting complexes increase the overall absorption cross section but slow down charge separation. This remarkable property can be explained with the available structural and spectroscopic information. The unique design is probably important for these cyanobacteria to efficiently switch between visible and far-red light.
A forward Brillouin fibre laser
Authors: Bashan Gil , Diamandi H. Hagai , Zehavi Elad , Sharma Kavita , London Yosef , Zadok Avi 
Published: June 2022

AbstractFibre lasers based on backward stimulated Brillouin scattering provide narrow linewidths and serve in signal processing and sensing applications. Stimulated Brillouin scattering in fibres takes place in the forward direction as well, with amplification bandwidths that are narrower by two orders of magnitude. However, forward Brillouin lasers have yet to be realized in any fibre platform. In this work, we report a first forward Brillouin fibre laser, using a bare off-the-shelf, panda-type polarisation maintaining fibre. Pump light in one principal axis provides Brillouin amplification for a co-propagating lasing signal of the orthogonal polarisation. Feedback is provided by Bragg gratings at both ends of the fibre cavity. Single-mode, few-modes and multi-mode regimes of operation are observed. The lasing threshold exhibits a unique environmental sensitivity: it is elevated when the fibre is partially immersed in water due to the broadening of forward Brillouin scattering spectra. The results establish a new type of fibre laser, with potential for ultra-high coherence and precision sensing of media outside the cladding.
Binding and structural basis of equine ACE2 to RBDs from SARS-CoV, SARS-CoV-2 and related coronaviruses
Authors: Xu Zepeng , Kang Xinrui , Han Pu , Du Pei , Li Linjie , Zheng Anqi , Deng Chuxia , Qi Jianxun , Zhao Xin , Wang Qihui , Liu Kefang , Gao George Fu 
Published: June 2022

AbstractThe origin and host range of SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), are important scientific questions as they might provide insight into understanding of the potential future spillover to infect humans. Here, we tested the binding between equine angiotensin converting enzyme 2 (eqACE2) and the receptor binding domains (RBDs) of SARS-CoV, SARS-CoV-2 prototype (PT) and variant of concerns (VOCs), as well as their close relatives bat-origin coronavirus (CoV) RaTG13 and pangolin-origin CoVs GX/P2V/2017 and GD/1/2019. We also determined the crystal structures of eqACE2/RaTG13-RBD, eqACE2/SARS-CoV-2 PT-RBD and eqACE2/Omicron BA.1-RBD. We identified S494 of SARS-COV-2 PT-RBD as an important residue in the eqACE2/SARS-COV-2 PT-RBD interaction and found that N501Y, the commonly recognized enhancing mutation, attenuated the binding affinity with eqACE2. Our work demonstrates that horses are potential targets for SARS-CoV-2 and highlights the importance of continuous surveillance on SARS-CoV-2 and related CoVs to prevent spillover events.
A ternary heterogeneous hydrogel with strength elements for resilient, self-healing, and recyclable epidermal electronics
Authors: Wang Ziya , Xu Xiuru , Xu Yingtian , Lin Waner , Peng Zhengchun 
Published: June 2022

AbstractEpidermal sensing devices, which mimic functionalities and mechanical properties of natural skin, offer great potential for real-time health monitoring via continuous checking of vital signs. However, most existing skin-mounted electronics use a flexible film with high elastic modulus, which hinders physical activity and causes interfacial delamination and skin irritation. The compliance of hydrogel-based devices can firmly conform to complex, curved surfaces without introducing excessive interfacial stresses. However, most hydrogels still suffer from the weakness of stable and reproducible sensing. In this work, we report a skin-friendly epidermal electronic made of a resilient, self-healing, and recyclable polyvinyl alcohol (PVA) hydrogel. The hydrogel is reinforced through a ternary heterogeneous network for good mechanical robustness while maintaining high stretchability and exceptional conformability. Simultaneously, the abundant dynamic hydrogen bonds give the hydrogel rapid self-healing ability. The assembled hydrogel epidermal electronic is able to stably monitor multiple physiological signals as well as sense the strain level of the skin motion and joint bending. The unique, versatile, environmental and biological friendly epidermal electronics will have broad applications in health care, human-machine interface, augmented reality, and so on.
Metal-organic framework modified hydrophilic polyvinylidene fluoride porous membrane for efficient degerming selective oil/water emulsion separation
Authors: Ye Qin , Xu Jia-Min , Zhang Yi-Jie , Chen Shu-Han , Zhan Xue-Qing , Ni Wang , Tsai Lung-Chang , Jiang Tao , Ma Ning , Tsai Fang-Chang 
Published: June 2022

AbstractDeveloping a new type of superhydrophilic/underwater superoleophobic oil/water separation membrane with high separation efficiency, high throughput and bacteria separation has essential theoretical and practical significance for treating oily and medical wastewater. This work modified commercial PVDF membranes by knife coating and cross-linking, and PVDF/PVA/LPB/MOF hybrid separation membranes are manufactured. Hydrophilic polyvinyl alcohol (PVA) endows the separation membrane with good hydrophilicity. Lauramidopropyl Betaine (LPB) enhances intermolecular hydrogen bonding and improves the mechanical properties of the membrane. A Metal-organic framework (MOF) with excellent biocompatibility, UiO-66-NH2, plays a vital role in the separation of bacteria. The results of the morphology and surface chemistry of characterization analysis show that the PVDF/PVA/LPB/MOF hybrid separation membrane exhibits excellent superhydrophilicity (with a contact angle of 2°) and high-water flux (15600 L/m2h) and high separation efficiency (99%), and the nature of filtering bacteria while separating oil. After modification, the separation efficiency increased from 30% to 99%, showing strong oil stain resistance. Our finding suggests that the new type of super-hydrophilic/underwater superoleophobic oil/water separation membrane has potential value in practical applications.
ReaLSAT, a global dataset of reservoir and lake surface area variations
Authors: Khandelwal Ankush , Karpatne Anuj , Ravirathinam Praveen , Ghosh Rahul , Wei Zhihao , Dugan Hilary A. , Hanson Paul C. , Kumar Vipin 
Published: June 2022

AbstractLakes and reservoirs, as most humans experience and use them, are dynamic bodies of water, with surface extents that increase and decrease with seasonal precipitation patterns, long-term changes in climate, and human management decisions. This paper presents a new global dataset that contains the location and surface area variations of 681,137 lakes and reservoirs larger than 0.1 square kilometers (and south of 50 degree N) from 1984 to 2015, to enable the study of the impact of human actions and climate change on freshwater availability. Within its scope for size and region covered, this dataset is far more comprehensive than existing datasets such as HydroLakes. While HydroLAKES only provides a static shape, the proposed dataset also has a timeseries of surface area and a shapefile containing monthly shapes for each lake. The paper presents the development and evaluation of this dataset and highlights the utility of novel machine learning techniques in addressing the inherent challenges in transforming satellite imagery to dynamic global surface water maps.
Presenting the Compendium Isotoporum Medii Aevi, a Multi-Isotope Database for Medieval Europe
Authors: Cocozza Carlo , Cirelli Enrico , Groß Marcus , Teegen Wolf-Rüdiger , Fernandes Ricardo 
Published: June 2022

AbstractHere we present theCompendium Isotoporum Medii Aevi (CIMA), an open-access database gathering more than 50,000 isotopic measurements for bioarchaeological samples located within Europe and its margins, and dating between 500 and 1500 CE. This multi-isotope (δ13C, δ15N, δ34S, δ18O, and87Sr/86Sr) archive of measurements on human, animal, and plant archaeological remains also includes a variety of supporting information that offer, for instance, a taxonomic characterization of the samples, their location, and chronology, in addition to data on social, religious, and political contexts. Such a dataset can be used to identify data gaps for future research and to address multiple research questions, including those related with studies on medieval human lifeways (i.e. human subsistence, spatial mobility), characterization of paleo-environmental and -climatic conditions, and on plant and animal agricultural management practices. Brief examples of such applications are given here and we also discuss how the integration of large volumes of isotopic data with other types of archaeological and historical data can improve our knowledge of medieval Europe.
The performance of ensemble-based free energy protocols in computing binding affinities to ROS1 kinase
Authors: Wan Shunzhou , Bhati Agastya P. , Wright David W. , Wade Alexander D. , Tresadern Gary , van Vlijmen Herman , Coveney Peter V. 
Published: June 2022

AbstractOptimization of binding affinities for compounds to their target protein is a primary objective in drug discovery. Herein we report on a collaborative study that evaluates a set of compounds binding to ROS1 kinase. We use ESMACS (enhanced sampling of molecular dynamics with approximation of continuum solvent) and TIES (thermodynamic integration with enhanced sampling) protocols to rank the binding free energies. The predicted binding free energies from ESMACS simulations show good correlations with experimental data for subsets of the compounds. Consistent binding free energy differences are generated for TIES and ESMACS. Although an unexplained overestimation exists, we obtain excellent statistical rankings across the set of compounds from the TIES protocol, with a Pearson correlation coefficient of 0.90 between calculated and experimental activities.
Understanding and predicting the functional consequences of missense mutations in BRCA1 and BRCA2
Authors: Aljarf Raghad , Shen Mengyuan , Pires Douglas E. V. , Ascher David B. 
Published: June 2022

AbstractBRCA1 and BRCA2 are tumour suppressor genes that play a critical role in maintaining genomic stability via the DNA repair mechanism. DNA repair defects caused by BRCA1 and BRCA2 missense variants increase the risk of developing breast and ovarian cancers. Accurate identification of these variants becomes clinically relevant, as means to guide personalized patient management and early detection. Next-generation sequencing efforts have significantly increased data availability but also the discovery of variants of uncertain significance that need interpretation. Experimental approaches used to measure the molecular consequences of these variants, however, are usually costly and time-consuming. Therefore, computational tools have emerged as faster alternatives for assisting in the interpretation of the clinical significance of newly discovered variants. To better understand and predict variant pathogenicity in BRCA1 and BRCA2, various machine learning algorithms have been proposed, however presented limited performance. Here we present BRCA1 and BRCA2 gene-specific models and a generic model for quantifying the functional impacts of single-point missense variants in these genes. Across tenfold cross-validation, our final models achieved a Matthew's Correlation Coefficient (MCC) of up to 0.98 and comparable performance of up to 0.89 across independent, non-redundant blind tests, outperforming alternative approaches. We believe our predictive tool will be a valuable resource for providing insights into understanding and interpreting the functional consequences of missense variants in these genes and as a tool for guiding the interpretation of newly discovered variants and prioritizing mutations for experimental validation.
Spatial distribution and ecological risk assessment of potentially toxic metals in the Sundarbans mangrove soils of Bangladesh
Authors: Islam Md Mahfuz , Akther Sayada Momotaz , Hossain Md Faruque , Parveen Zakia 
Published: June 2022

AbstractAt present, there are growing concerns over the increasing release of trace metals in the Sundarbans mangrove areas in Bangladesh due to nearby shipbreaking and metallurgical industries, untreated waste discharge, navigation activities, and other natural processes that deposit trace metals into soils. The current study investigated the spatial distribution, contamination level, and ecotoxicity of eight trace metals (Fe, Mn, Cu, Zn, Pb, Cd, Cr, Ni) in Sundarbans soils. Results revealed that all the trace metals except Cr were present in higher concentrations compared to Earth’s shale and/or upper continental crust. Principal component analysis and Pearson correlation showed strong positive correlations (p < 0.05) between Fe, Mn, Cu, and Zn; Ni with Mn and Cr. There were significant associations (p < 0.05) of % clay and total organic carbon (TOC) with Pb-Ni-Cr and negative correlations of pH with all the trace metals. The hierarchical cluster analysis grouped Pb, Ni, and Cd into one distinct cluster, suggesting they are derived from the same sources, possibly from anthropogenic activities. Geo accumulation index (I-geo), enrichment factor (EF), contamination factor (CF), and spatial distribution showed moderately polluted soils with Ni, Pb, and Cd (EF = 3–7.4, CF = 1–2.8, I-geo = 0–0.9) and low pollution by Zn, Cu, Fe, and Mn (EF < 3, CF < 1, I-geo < 0). The ecological risk index (RI) revealed that S-4 (RI = 114.02) and S-5 (RI = 100.04) belonged to moderate risk, and other areas posed a low risk (RI < 95). The individual contribution of Cd (25.9–73.7%), Pb (9.2–29.1%), and Ni (9.6–26.4%) to RI emphasized these metals were the foremost concern in the Sundarbans mangroves due to their long persistence time and high toxicity, even if they were present in low concentrations.
Profiling gut microbiota and bile acid metabolism in critically ill children
Authors: Kean Iain Robert Louis , Wagner Joseph , Wijeyesekera Anisha , De Goffau Marcus , Thurston Sarah , Clark John A. , White Deborah K. , Ridout Jenna , Agrawal Shruti , Kayani Riaz , O’Donnell Roddy , Ramnarayan Padmanabhan , Peters Mark J. , Klein Nigel , Holmes Elaine , Parkhill Julian , Baker Stephen , Pathan Nazima 
Published: June 2022

AbstractBroad-spectrum antimicrobial use during the treatment of critical illness influences gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary to secondary bile acids. We previously observed reduced fermentation capacity in the faecal microbiota of critically ill children upon hospital admission. Here, we further explore the timecourse of the relationship between the microbiome and bile acid profile in faecal samples collected from critically ill children. The microbiome was assayed by sequencing of the 16S rRNA gene, and faecal water bile acids were measured by liquid chromatography mass spectrometry. In comparison to admission faecal samples, members of theLachnospiraceaerecovered during the late-acute phase (days 8–10) of hospitalisation. Patients with infections had a lower proportion ofLachnospiraceaein their gut microbiota than controls and patients with primary admitting diagnoses. Keystone species linked to ecological recovery were observed to decline with the length of PICU admission. These species were further suppressed in patients with systemic infection, respiratory failure, and undergoing surgery. Bile acid composition recovers quickly after intervention for critical illness which may be aided by the compositional shift inLachnospiraceae. Our findings suggest gut microbiota recovery can be readily assessed via measurement of faecal bile acids.