bluuebunny/crossref_metadata_2025_split huggingface dataset:
A local translation program regulates centriole amplification in the airway epithelium
Authors: Liu Helu , Li Huijun , Jiang Zhihua , Jin Shibo , Song Rui , Yang Ying , Li Jun , Huang Jingshu , Zhang Xiaoqing , Dong Xuesong , Mori Munemasa , Fritzler Marvin J , He Lin , Cardoso Wellington , Lu Jining 
Published: January 2022

AbstractBiogenesis of organelles requires targeting of a subset of proteins to specific subcellular domains by signal peptides or mechanisms controlling mRNA localization and local translation. How local distribution and translation of specific mRNAs for organelle biogenesis is achieved remains elusive and likely to be dependent on the cellular context. Here we identify Trinucleotide repeat containing-6a (Tnrc6a), a component of the miRNA pathway, distinctively localized to apical granules of differentiating airway multiciliated cells (MCCs) adjacent to centrioles. In spite of being enriched in TNRC6A and the miRNA-binding protein AGO2, they lack enzymes for mRNA degradation. Instead, we found these apical granules enriched in components of the mRNA translation machinery and newly synthesized proteins suggesting that they are specific hubs for target mRNA localization and local translation in MCCs. Consistent with this,Tnrc6aloss of function prevented formation of these granules and led to a broad reduction, rather than stabilization of miRNA targets. These included downregulation of key genes involved in ciliogenesis and was associated with defective multicilia formation both in vivo and in primary airway epithelial cultures. Similar analysis of Tnrc6a disruption in yolk sac showed stabilization of miRNA targets, highlighting the potential diversity of these mechanisms across organs.HighlightsTnrc6ais expressed in the lung selectively in differentiating multiciliated cells (MCC) adjacent to centrioles.TNRC6A localizes to apical granules containing AGO2, miRNAs and their targets, but lacking mRNA degradation enzymes.TNRC6A granules are enriched in components of the mRNA translation machinery and show evidence of concentrated newly-synthesized proteinsLoss ofTnrc6ain the lung leads to reduction, not stabilization of miRNA targets.Tnrc6ais required for efficient centriole amplification and multicilia formation.
Microbial GWAS studies revealing combinations of Omicron RBD mutations existed and may contribute to antibody evasion and ACE2 binding
Authors: Ou Xumin , Yang Zhishuang , Zhu Dekang , Mao Sai , Wang Mingshu , Jia Renyong , Chen Shun , Liu Mafeng , Yang Qiao , Wu Ying , Zhao Xinxin , Zhang Shaqiu , Huang Juan , Gao Qun , Liu Yunya , Zhang Ling , Peopplenbosch Maikel , Pan Qiuwei , Cheng Anchun 
Published: January 2022

AbstractSince Omicron variant of SARS-CoV-2 was first detected in South Africa (SA), it has now dominated in United Kingdom (UK) of Europe and United State (USA) of North America. A prominent feature of this variant is the gathering of spike protein mutations, in particularly at the receptor binding domain (RBD). These RBD mutations essentially contribute to antibody resistance of current immune approaches. During global spillover, combinations of RBD mutations may exist and synergistically contribute to antibody resistance in fact. Using three geographic-stratified genome wide association studies (GWAS), we observed that RBD combinations exhibited a geographic pattern and genetical associated, such as five common mutations in both UK and USA Omicron, six or two specific mutations in UK or USA Omicron. Although the UK specific RBD mutations can be further classified into two separated sub-groups of combination based on linkage disequilibrium analysis. Functional analysis indicated that the common RBD combinations (fold change, -11.59) alongside UK or USA specific mutations significantly reduced neutralization (fold change, -38.72, -18.11). As RBD overlaps with angiotensin converting enzyme 2(ACE2) binding motif, protein-protein contact analysis indicated that the common RBD mutations enhanced ACE2 binding accessibility and were further strengthened by UK or USA-specific RBD mutations. Spatiotemporal evolution analysis indicated that UK-specific RBD mutations largely contribute to global spillover. Collectively, we have provided genetic evidence of RBD combinations and estimated their effects on antibody evasion and ACE2 binding accessibility.
Cannabis Use and Sleep Quality in Daily Life: a Daily Diary Study of Adults Starting Cannabis for Health Concerns
Authors: Tervo-Clemmens Brenden , Schmitt William , Wheeler Grace , Cooke Megan , Schuster Randi M. , Hickey Sarah , Pachas Gladys , Evins A. Eden , Gilman Jodi 
Published: January 2022

AbstractBackgroundLegalization of cannabis for medical uses has proceeded without well-controlled studies. Real world patterns of medical cannabis use are highly variable and rarely overseen by a physician. Smartphone assessments that capture ecologically valid patterns of medical cannabis use and health symptoms may help clarify risks and benefits.MethodsAs part of a larger, randomized trial (NCT03224468), adults (N=181) seeking cannabis for insomnia, pain, or anxiety or depressive symptoms were randomized to obtain a medical cannabis card immediately (MCC) or to a waitlist control (WLC) and completed 12-weeks of daily web-based surveys on cannabis use and three health outcomes: sleep, pain, and depressive symptoms.ResultsCompletion rates in this long-term, daily survey design were high (median completed assessments: 72 out of 90 days). Daily reports of cannabis use were consistent with monthly interview assessments and urinalysis. The MCC group increased cannabis use frequency following randomization, while WLC did not. Within the MCC group, self-reported sleep quality was significantly higher on cannabis use days, compared to nonuse days. The MCC group displayed long-term sleep improvements, paralleled by increased cannabis frequency. Daily associations between cannabis use and self-reported pain or depressive symptoms were not significant.ConclusionCannabis use is associated with same day improvements in self-reported sleep quality, but not pain or depressive symptoms, although sleep improvements occurred within the context of potentially risky increases in use. Long-term, web-based assessments of cannabis appear valid and feasible, providing a robust method for future real-world effectiveness studies with expanded and objective measures.Funding/SupportThis work was funded by R01DA042043; PI: JMG.
Auto-Detection and Segmentation of Involved Lymph Nodes in HPV-Associated Oropharyngeal Cancer Using a Convolutional Deep Learning Neural Network
Authors: Taku Nicolette , Wahid Kareem A. , van Dijk Lisanne V. , Sahlsten Jaakko , Jaskari Joel , Kaski Kimmo , Fuller C. David , Naser Mohamed A. 
Published: January 2022

AbstractPurposeSegmentation of involved lymph nodes on head and neck computed tomography (HN-CT) scans is necessary for the radiotherapy treatment planning of human papilloma virus (HPV) associated oropharynx cancers (OPC). We aimed to train a deep learning convolutional neural network (DL-CNN) to identify and segment involved lymph nodes on contrast-enhanced HN-CT scans.Methods90 patients who underwent levels II-IV neck dissection for newly diagnosed, clinically node-positive, HPV-OPC were identified. Ground-truth segmentation of all radiographically and pathologically involved nodes was manually performed on pre-surgical HN-CT scans, which were randomly divided into training/validation dataset (n=70) and testing dataset (n=20). A 5-fold cross validation was used to train 5 separate DL-CNN sub-models based on a residual U-net architecture. Validation and testing segmentation masks were compared to ground-truth segmentation masks using overlap-based, volume-based, and distance-based metrics. A lymph auto-detection model was developed by thresholding segmentation model outputs, and 20 node-negative HN-CT scans were added to the test set to further evaluate auto-detection capabilities. Model discrimination of lymph node “positive” and “negative” HN-CT scans was evaluated using the area under the receiver operating characteristic curve (AUC).ResultsIn the DL-CNN validation phase, all sub-models yielded segmentation masks with median DSC ≥ 0.90 and median volume similarity score of ≥ 0.95. In the testing phase, the DL-CNN produced consensus segmentation masks with median Dice of 0.92 (IQR, 0.89-0.95), median volume similarity of 0.97 (IQR, 0.94-0.99), and median Hausdorff distance of 4.52 mm (IQR, 1.22-8.38). The detection model achieved an AUC of 0.98.ConclusionThe results from this single-institution study demonstrate the successful automation of lymph node segmentation for patients with HPV-OPC using a DL-CNN. Future studies, including external validation using a larger dataset, are necessary to clarify the role of the DL-CNN in the routine radiation oncology treatment planning workflow.
STAT3 regulates cytokine production downstream of TNFR1 in part by inducing expression of TNFAIP3/A20
Authors: Antonia Ricardo , Karelehto Eveliina , Toriguchi Kan , Matli Mary , Warren Robert , Pfeffer Lawrence M. , Donner David B. 
Published: January 2022

AbstractBackgroundPrevious work demonstrated that the Signal Transducer and Activator of Transcription 3 (STAT3) is activated downstream of the Type 1 TNF Receptor. However, whether and how STAT3 regulates gene expression downstream of TNFR1 has not been elucidated.MethodsGlobal transcriptome analysis by RNA sequencing was performed in wild type and STAT3 knockout mouse embryonic fibroblasts (MEFs) stimulated with TNF. The fold changes in gene expression were assessed bioinformatically. Results of the RNA sequencing were validated at the protein level by using multiplex cytokine assays and immunoblotting.ResultsStimulation of MEFs with TNF or an agonist antibody to TNFR1 activated STAT3, and this was inhibited by pharmacological inhibition of Jak2 and cSrc. At 4 hours after TNF stimulation, STAT3 knockout MEFs had a greater level than WT MEFs of induction of the chemokines Ccl2, Cxcl1 and Cxcl10 at the RNA and protein levels. Mechanistically, this was due STAT3 promoting the expression of Tnfaip3/A20, a ubiquitin modifying enzyme that inhibits inflammation, in wild-type MEFs at early timepoints after TNFR1 stimulation. In STAT3 knockout MEFs TNF failed to induce the expression of Tnfaip3/A20 or GM-CSF when acting through TNFR1. Expression of A20 into STAT3 knockout MEFs suppressed cytokine expression.ConclusionSTAT3 limits the induction of Ccl2, Cxcl1 and Cxcl10 in response to TNFR1 activation by promoting the expression of Tnfaip3/A20. On the other hand, STAT3 promotes the expression of GM-CSF in response to TNFR1 stimulation. These results show that STAT3 modulates inflammatory signaling by TNF in normal cells.
SAIBR: A simple, platform-independent method for spectral autofluorescence correction
Authors: Rodrigues Nelio T.L. , Bland Tom , Borrego-Pinto Joana , Ng KangBo , Hirani Nisha , Gu Ying , Foo Sherman , Goehring Nathan W. 
Published: January 2022

AbstractBiological systems are increasingly viewed through the lens of mathematics, physics, and systems approaches that demand accurate quantification of gene expression and local protein concentrations. Such approaches have benefited greatly from the revolution in genetic engineering sparked by CRISPR/Cas9. By facilitating the tagging of genes at their genomic loci, CRISPR/Cas9 allows us to use fluorescence to monitor proteins that are expressed at or near endogenous levels under native regulatory control. However, due to their typically lower expression levels, quantitative experiments using endogenously-tagged genes can run into limits imposed by autofluorescence (AF). AF is often a particular challenge in the illumination bands occupied by the most efficient fluorescent proteins (GFP, mNeonGreen). Stimulated by our work in C. elegans, we describe and validate Spectral Autofluorescence Image correction By Regression (SAIBR), a simple, platform-independent protocol, and associated GUI-based FIJI plugin to correct for autofluorescence using standard filter sets and illumination conditions. Fully validated for use in C. elegans embryos and tested in diverse systems, including starfish oocytes and fission yeast, SAIBR achieves accurate quantitation of fluorophore signal and enables reliable detection and quantification of even weakly expressed proteins. Thus, SAIBR provides a highly accessible, low barrier way to incorporate AF correction as standard for researchers working on a broad variety of cell and developmental systems.Summary StatementImplemented as an easy-to-use Fiji Plugin, SAIBR provides effective autofluorescence correction for cells and tissues using standard imaging conditions.
Ancient herpes simplex 1 genomes reveal recent viral structure in Eurasia
Authors: Guellil Meriam , van Dorp Lucy , Inskip Sarah A. , Dittmar Jenna M. , Saag Lehti , Tambets Kristiina , Hui Ruoyun , Rose Alice , D’Atanasio Eugenia , Kriiska Aivar , Varul Liivi , Koekkelkoren A.M.H.C. , Goldina Rimma D. , Cessford Craig , Solnik Anu , Metspalu Mait , Krause Johannes , Herbig Alexander , Robb John E. , Houldcroft Charlotte J. , Scheib Christiana L. 
Published: January 2022

SummaryHuman herpes simplex virus 1 (HSV-1), a life-long infection spread by oral contact, today infects a majority of adults globally1, yet no ancient HSV-1 genomes have yet been published. Phylogeographic clustering of sampled diversity into European, pan-Eurasian, and African groups2, 3 has suggested that the virus co-diverged with anatomically modern humans migrating out of Africa4, although a much younger origin has also been proposed5. The lack of ancient HSV-1 genomes, high rates of recombination, and high mobility of humans in the modern era have impeded the understanding of HSV-1’s evolutionary history. Here we present three full ancient European HSV-1 genomes and one partial genome, dating to between the 3rd and 17th century CE, sequenced to up to 9.5× with paired human genomes up to 10.16×. These HSV-1 strains fall within modern Eurasian diversity. We estimate a mean mutation rate of 7.6 × 10-7 - 1.13 × 10-6 for non-African diversity leading to an estimated age of sampled modern Eurasian diversity to 4.68 (3.87 - 5.65) kya. Extrapolation of these rates indicate the age of sampled HSV-1 to 5.29 (4.60-6.12 kya, suggesting lineage replacement coinciding with late Neolithisation and implicating Bronze Age migrations6 in the distribution of HSV-1 through Eurasia.
Whole genome analysis sheds light on the genetic origin of Huns, Avars and conquering Hungarians
Authors: Maróti Zoltán , Neparáczki Endre , Schütz Oszkár , Maár Kitti , Varga Gergely I. B. , Kovács Bence , Kalmár Tibor , Nyerki Emil , Nagy István , Latinovics Dóra , Tihanyi Balázs , Marcsik Antónia , Pálfi György , Bernert Zsolt , Gallina Zsolt , Horváth Ciprián , Varga Sándor , Költő László , Raskó István , Nagy Péter L. , Balogh Csilla , Zink Albert , Maixner Frank , Götherström Anders , George Robert , Szalontai Csaba , Szenthe Gergely , Gáll Erwin , Kiss Attila P. , Rácz Zsófia , Gulyás Bence , Kovacsóczy Bernadett Ny. , Gaál Szilárd Sándor , Tomka Péter , Török Tibor 
Published: January 2022

SummaryHuns, Avars and conquering Hungarians were Migration Period nomadic groups which arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on historical data each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations has been debated. In this study we have sequenced 9 Hun, 143 Avar and 113 Hungarian conquest period samples, and identified three core populations, representing immigrants from each period, with no recent European ancestry. Our results suggest that this “immigrant core” of both Huns and Avars originated in present day Mongolia, and their origin can be traced back to Xiongnus. On the other hand, the “immigrant core” of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians and descendants of late Xiongnus. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups we identified that the majority of the individuals from each period were local residents, harboring “native European” ancestry.
Improving Small Molecule pKa Prediction Using Transfer Learning with Graph Neural Networks
Authors: Mayr Fritz , Wieder Marcus , Wieder Oliver , Langer Thierry 
Published: January 2022

AbstractEnumerating protonation states and calculating micro-state pKa values of small molecules is an important yet challenging task for lead optimization and molecular modeling. Commercial and non-commercial solutions have notable limitations such as restrictive and expensive licenses, high CPU/GPU hour requirements, or the need for expert knowledge to set up and use. We present a graph neural network model that is trained on 714,906 calculated mico-state pKa predictions from molecules obtained from the ChEMBL database. The model is fine-tuned on a set of 5,994 experimental pKa values significantly improving its performance on two challenging test sets. Combining the graph neural network model with Dimorphite-DL, an open-source program for enumerating ionization states, we have developed the open-source Python package pkasolver, which is able to generate and enumerate protonation states and calculate micro-state pKa values with high accuracy.
Cell cycle dynamics controls fluidity of the developing mouse neuroepithelium
Authors: Bocanegra-Moreno Laura , Singh Amrita , Hannezo Edouard , Zagorski Marcin , Kicheva Anna 
Published: January 2022

AbstractAs organs are remodelled by morphogenetic changes and pattern formation during development, their material properties may change. To address whether and how this occurs in the mouse neural tube, we combined highly resolved mosaic analysis, biophysical modelling and perturbation experiments. We found that at early developmental stages the neuroepithelium surprisingly maintains both high junctional tension and high fluidity. This is achieved via a previously unrecognized mechanism in which interkinetic nuclear movements generate cell area dynamics that drive extensive cell rearrangements. Over time, the proliferation rate declines, effectively solidifying the tissue. Thus, unlike well-studied jamming transitions, the solidification we uncovered resembles a glass transition that depends on the dynamics of stresses generated by proliferation and differentiation. This new link between epithelial fluidity, interkinetic movements and cell cycle dynamics has implications for the precision of pattern formation and could be relevant to multiple developing tissues.
Myogenic regulatory factors MyoD and Myf5 are required for dorsal aorta formation and angiogenic sprouting
Authors: Paulissen Eric , Martin Benjamin L. 
Published: January 2022

ABSTRACTThe vertebrate embryonic midline vasculature forms in close proximity to the developing skeletal muscle, which originates in the somites. Angioblasts migrate from bilateral positions along the ventral edge of the somites until they meet at the midline, where they sort and differentiate into the dorsal aorta and the cardinal vein. This migration occurs at that the same time that myoblasts in the somites are beginning to differentiate into skeletal muscle, a process which requires the activity of the basic helix loop helix (bHLH) transcription factors Myod and Myf5. Here we examined vasculature formation in myod and myf5 mutant zebrafish. In the absence of skeletal myogenesis, angioblasts migrate normally to the midline but form only the cardinal vein and not the dorsal aorta. The phenotype is due to the failure to activate vascular endothelial growth factor ligand vegfaa expression in the somites, which in turn is required in the adjacent angioblasts for dorsal aorta specification. Myod and Myf5 cooperate with Hedgehog signaling to activate and later maintain vegfaa expression in the medial somites, which is required for angiogenic sprouting from the dorsal aorta. Our work reveals that the early embryonic skeletal musculature in teleosts evolved to organize the midline vasculature during development.Summary statementThe myogenic transcription factors MyoD and Myf5 have a novel function in inducing the artery through regulation of Vegf.
Green synthesis and use of copper oxide nanoparticles to prepare a highly thermal, antimicrobial, and anticorrosion hybrid coating for mild steel under electron beam irradiation
Authors: Mousaa I.M. , Abdelreheim N.A. , Elnaggar S.A. , Fathy Rasha M. 
Published: January 2022

Purpose
The purpose of this study is to prepare copper oxide nanoparticles (CuO NPs) in an easy and efficient way using a natural and environmentally friendly substance like ascorbic acid. Various concentrations of these nanoparticles were then added to solvent-free coating formulations to produce highly hydrophobic, corrosion-resistant and antimicrobial hybrid coatings. These hybrid formulations were also used to coat the spent fuel casks for their integrity.

Design/methodology/approach
The hybrid coated films were then characterized by X-ray diffraction, Fourier transform infrared spectroscopy (FT-IR), water contact angle and Scanning electron microscope (SEM). In addition, different measurements, namely, mechanical, physical, chemical, thermal, corrosion tests, open circuit potential and antimicrobial activity of these hybrid films were performed.

Findings
The results showed that the copper oxide was prepared at nanometer scales with good homogeneity and diffusion in the epoxy acrylate matrix. It also showed that some hybrid coatings have high corrosion resistance, strong hardness, excellent water resistance, remarkable antimicrobial activity and high thermal stability compared to virgin epoxy acrylates.

Originality/value
The formula containing 0.5% CuO NPs was found to provide the highest corrosion protection and antimicrobial activity for mild steel in 3.5% sodium chloride (NaCl).
Mutual proximity and heterogeneity in peer effects of farmers' technology adoption: evidence from China's soil testing and formulated fertilization program
Authors: Xu Zhigang , Zhang Kerong , Zhou Li , Ying Ruiyao 
Published: January 2022

PurposeWhile the peer effects of technology adoption are well established, few studies have considered the variation in peer effects resulting from the mutual proximity between leaders and followers and the heterogeneity of farmers' learning technology. This study addresses the gap in the literature by analyzing the peer effects of technology adoption among Chinese farmers.Design/methodology/approachDrawing on a government-led soil testing and formulated fertilization program, this study uses survey data of farmers from three Chinese provinces to examine the peer effects of technology adoption. This study uses a probit model to examine how mutual proximity influences peer effects and their heterogeneity. Accordingly, farmers were divided into two groups, namely small- and large-scale farmers, and then into leaders or followers depending on whether they were selected by the government as model farmers.FindingsBoth small- and large-scale farmers are more likely to use formula fertilizer if their peers do so. However, a large-scale farmer is more likely to adopt formula fertilizer if the average adoption behavior of other large-scale model (leader) farmers is higher, while a small-scale farmer is more likely to adopt formula fertilizer if other small-scale non-model (follower) farmers have higher average adoption behavior. Moreover, the peer effect was weakened by geographic distance among small-scale farmers and by economic distance among large-scale farmers.Originality/valueThis study elucidates the means of optimizing social learning and technology adoption among farmers.