bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zunongwangia pacifica sp. nov., isolated from surface seawater of the Western Pacific Ocean
Authors: Chen Yongqing , Liu Tianqi , Lai Qiliang , Dong Chunming , Shao Zongze 
Published: November 2022

Zunongwangia

is a group of marine bacteria with important industrial application potential and ecological functions. In this study, a Gram-stain-negative, rod-shaped, non-motile, strictly aerobic and bright yellow pigmented bacterial strain within this genus, designated C2-37M9T, was isolated from a surface seawater sample from the Philippine Basin in the Western Pacific Ocean. Strain C2-37M9T grew at 10–44 °C (optimum, 28–30 °C), pH 6–9 (pH 7) and in the presence of 0–12 % NaCl (w/v; 2–3 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that it belonged to the genus

Zunongwangia

and had 95.7–98.7 % sequence similarity to all type strains of this genus, with the highest value corresponding to

Zunongwangia profunda

(98.7 %). Digital DNA–DNA hybridization, average nucleotide identity and average amino acid identity values between strain C2-37M9T and all valid type strains were 27.5–32.3, 83.8–86.7 and 86.9–89.0 %, respectively. The principal fatty acids (>5 %) were iso-C15 : 0, iso-C17 : 0 3-OH, anteiso-C15 : 0, summed feature 9 (C16 : 0 10-methyl and/or iso-C17 : 1
ω9c), iso-C15 : 1 G and summed feature 3 (C16 : 1
ω6c and/or C16 : 1
ω7c). The predominant respiratory quinone was MK-6. The polar lipids were one phosphatidylethanolamine, two unknown glycolipids, three unidentified aminolipids and six unidentified lipids. The genomic DNA G+C content of strain C2-37M9T was 36.7 mol%. Based on phylogenetic results and genomic-based relatedness indices, as well as phenotypic and genotypic characteristics, strain C2-37M9T represents a novel species within the genus

Zunongwangia

, for which the name Zunongwangia pacifica sp. nov. is proposed. The type strain is C2-37M9T (=MCCC M21534T=KCTC 82852T).
ShaPRS: Leveraging shared genetic effects across traits or ancestries improves accuracy of polygenic scores
Authors: Kelemen M. , Vigorito E. , Fachal L. , Anderson C. A. , Wallace C. 
Published: November 2022

AbstractWe present shaPRS, a novel method that leverages widespread pleiotropy between traits, or shared genetic effects across ancestries, to improve the accuracy of polygenic scores. The method uses genome-wide summary statistics from two diseases or ancestries to improve the genetic effect estimate and standard error at SNPs where there is homogeneity of effect between the two datasets. When there is significant evidence of heterogeneity, the genetic effect from the disease or population closest to the target population is maintained. We show via simulation and a series of real-world examples that shaPRS substantially enhances the accuracy of PRS for complex diseases and greatly improves PRS performance across ancestries. shaPRS is a PRS pre-processing method that is agnostic to the actual PRS generation method and, as a result, it can be integrated into existing PRS generation pipelines and continue to be applied as more performant PRS methods are developed over time.
A CNN-Transformer Deep Learning Model for Real-time Sleep Stage Classification in an Energy-Constrained Wireless Device
Authors: Yao Zongyan , Liu Xilin 
Published: November 2022

AbstractThis paper proposes a deep learning (DL) model for automatic sleep stage classification based on single-channel EEG data. The DL model features a convolutional neural network (CNN) and transformers. The model was designed to run on energy and memory-constrained devices for real-time operation with local processing. The Fpz-Cz EEG signals from a publicly available Sleep-EDF dataset are used to train and test the model. Four convolutional filter layers were used to extract features and reduce the data dimension. Then, transformers were utilized to learn the time-variant features of the data. To improve performance, we also implemented a subject specific training before the inference (i.e., prediction) stage. With the subject specific training, the F1 score was 0.91, 0.37, 0.84, 0.877, and 0.73 for wake, N1-N3, and rapid eye movement (REM) stages, respectively. The performance of the model was comparable to the state-of-the-art works with significantly greater computational costs. We tested a reduced-sized version of the proposed model on a low-cost Arduino Nano 33 BLE board and it was fully functional and accurate. In the future, a fully integrated wireless EEG sensor with edge DL will be developed for sleep research in pre-clinical and clinical experiments, such as real-time sleep modulation.
Comparison of LIAISON QuantiFERON-TB Gold Plus with QuantiFERON-TB Gold Plus
Authors: Kadkhoda Kamran , Dee Matthew , Simeone John 
Published: November 2022

AbstractWith the large global burden of latent tuberculosis (TB) infection (LTBI), screening for LTBI for various reasons has become standard practice including the low-prevalence settings.The results showed acceptable intra- and inter-run precision as well as cutoff verification across the two analyzers at the afore-mentioned levels (Table 1). Overall, the LIAISON QFT-Plus showed better inter- and intra-run precision compared with QFT-Plus when comparing low-positive TB1/2 samples; however, coefficient of variation (CVs) less than 20% are generally acceptable for any automated test. Cutoff verification showed CVs for QFT-Plus TB1 and TB2, QFT-Plus LIAISON TB1 and TB2 of 5.2%, 4.1%, 5.2%, 5.4%, respectively, demonstrating robustness around the cutoffs.Altogether, the two methods were highly comparable. LIAISON QFT-Plus is a suitable alternative to batch testing (e.g., using DSX) in high-volume laboratories.
Inability to work following COVID-19 vaccination among healthcare workers - an important aspect for future booster vaccinations
Authors: Reusch Julia , Wagenhäuser Isabell , Gabel Alexander , Höhn Anna , Lâm Thiên-Trí , Krone Lukas B. , Frey Anna , Schubert-Unkmeir Alexandra , Dölken Lars , Frantz Stefan , Kurzai Oliver , Vogel Ulrich , Krone Manuel , Petri Nils 
Published: November 2022

ABSTRACTBackgroundCOVID-19 vaccination is a key prevention strategy to reduce the spread and severity of SARS-CoV-2 infections, especially among highly exposed healthcare workers (HCWs). However, vaccine-related inability to work among HCWs could overstrain healthcare systems.MethodsThis study examined sick leave and intake of pro re nata (PRN) medication after the first, second and third COVID-19 vaccination in HCWs. Subgroup analyses were performed for different vaccines, gender, healthcare professions, and for HCWs aged at least 30 years. Data was collected by using an electronic questionnaire.FindingsAmong 1,704 HCWs enrolled, in total 595 (34·9%) HCWs were on sick leave following at least one COVID-19 vaccination, leading to a total number of 1,550 sick days. Both the absolute sick days and the rate of HCWs on sick leave significantly increased with each subsequent vaccination. Comparing BNT162b2mRNA and mRNA-1273 the difference in sick leave was not significant after the second dose, but mRNA-1273 induced a significantly longer and more frequent sick leave after the third.InterpretationA considerable number of HCWs have been on sick leave after COVID-19 vaccination, staff absences increase with each additional dose, depend on the vaccine, and vary between HCWs’ gender, and profession. In the light of further COVID-19 infection waves and booster vaccinations, there is a risk of additional staff shortages due to post-vaccination inability to work, which could acutely overload healthcare systems and jeopardise patient care. These findings will aid further vaccination campaigns to minimise the impact of staff absences on the healthcare system.FundingThis study was funded by the Federal Ministry for Education and Science (BMBF) via a grant provided to the University Hospital of Wuerzburg by the Network University Medicine on COVID-19 (B-FAST, grant-No 01KX2021) as well as by the Free State of Bavaria with COVID-research funds provided to the University of Wuerzburg, Germany. Nils Petri is supported by the German Research Foundation (DFG) funded scholarship UNION CVD.
Expanding the Huntington’s disease research toolbox; validated subdomain protein constructs for biochemical and structural investigation of huntingtin
Authors: Alteen Matthew G. , Deme Justin C. , Alvarez Claudia P. , Loppnau Peter , Hutchinson Ashley , Seitova Alma , Chandrasekaran Renu , Ramos Eduardo Silva , Secker Christopher , Alqazzaz Mona , Wanker Erich E. , Lea Susan M. , Arrowsmith Cheryl H , Harding Rachel J. 
Published: November 2022

AbstractHuntington’s disease is characterised by CAG expansion in the huntingtin gene above a critical threshold of~35 repeats, resulting in polyglutamine expansion of the huntingtin protein (HTT). The biological role of wildtype HTT and the associated mechanisms of disease pathology caused by expanded HTT remain incompletely understood, in part, due to challenges characterising interactions between HTT and putative binding partners. Here we describe a biochemical toolkit of rationally designed, high-quality recombinant HTT subdomains; one spanning the N-terminal HEAT and bridge domains (NTD) and the second spanning the C-terminal HEAT domain (CTD). Using biophysical methods and cryo-electron microscopy, we show these smaller subdomains are natively folded and can associate to reconstitute a functional full-length HTT structure capable of forming a near native-like complex with 40 kDa HTT-associated protein (HAP40). We report biotin-tagged variants of these subdomains, as well as full-length HTT, that permit immobilisation of each protein for quantitative biophysical assays without impacting protein quality. We demonstrate the CTD alone can form a stable complex when co-expressed with HAP40, which can be structurally resolved. The CTD-HAP40 complex binds the NTD, with a dissociation constant of approximately 10 nM as measured by bio-layer interferometry. We validate the interaction between the CTD and HAP40 using a luciferase two-hybrid assay and use subdomain constructs to demonstrate their respective stabilization of HAP40 in cells. These open-source biochemical tools will enable the wider HD community to study fundamental HTT biology, discover new macromolecular or small-molecule binding partners and map interaction sites across this very large protein.
SnRK1 inhibits anthocyanin biosynthesis through both transcriptional regulation and direct phosphorylation and dissociation of the MYB/bHLH/TTG1 MBW complex
Authors: Broucke Ellen , Vi Dang Thi Tuong , Li Yi , Hulsmans Sander , Van Leene Jelle , De Jaeger Geert , Hwang Ildoo , Van den Ende Wim , Rolland Filip 
Published: November 2022

AbstractPlants have evolved an extensive specialized secondary metabolism. The colorful flavonoid anthocyanins, for example, not only stimulate flower pollination and seed dispersal but also protect different tissues against high light, UV- and oxidative stress. Their biosynthesis is highly regulated by environmental and developmental cues and induced by high sucrose levels. Expression of the biosynthetic enzymes involved is controlled by a transcriptional MBW complex, comprising (R2R3) MYB- and bHLH-type transcription factors (TF) and the WD40 repeat protein TTG1. Anthocyanin biosynthesis is obviously useful but also carbon- and energy-intensive and non-vital. Consistently, the SnRK1 protein kinase, a metabolic sensor activated in carbon- and energy-depleting stress conditions, represses anthocyanin biosynthesis. Here we show thatArabidopsisSnRK1 represses MBW complex activity both at the transcriptional and post-translational level. In addition to repressing expression of the key transcription factor MYB75/PAP1, SnRK1 activity triggers MBW complex dissociation, associated with loss of target promoter binding, MYB75 protein degradation and nuclear export of TTG1. We also provide evidence for direct interaction with and phosphorylation of multiple MBW complex proteins. These results indicate that repression of expensive anthocyanin biosynthesis is an important strategy to save energy and redirect carbon flow to more essential processes for survival in metabolic stress conditions.
Isolated catatonia-like executive dysfunction in mice with forebrain-specific loss of myelin integrity
Authors: Arinrad Sahab , Depp Constanze , Siems Sophie B. , Sasmita Andrew Octavian , Eichel Maria A. , Ronnenberg Anja , Hammerschmidt Kurt , Lüders Katja A. , Werner Hauke B. , Ehrenreich Hannelore , Nave Klaus-Armin 
Published: November 2022

ABSTRACTA key feature of advanced brain aging includes structural defects of intracortical myelin that are associated with secondary neuroinflammation. A similar pathology is seen in specific myelin mutant mice that model ‘advanced brain aging’ and exhibit a range of behavioral abnormalities. However, the cognitive assessment of these mutants is problematic because myelin-dependent motor-sensory functions are required for quantitative behavioral readouts. To better understand the role of cortical myelin integrity for higher brain functions, we generated mice lackingPlp1, encoding the major integral myelin membrane protein, selectively in ventricular zone stem cells of the mouse forebrain. In contrast to conventionalPlp1null mutants, subtle myelin defects were restricted to the cortex, hippocampus and underlying callosal tracts. Moreover, forebrain-specificPlp1mutants exhibited no defect of basic motor-sensory performance at any age tested. Surprisingly, several behavioral alterations reported for conventionalPlp1null mice (Gould et al., 2018) were absent and even social interactions appeared normal. However, with novel behavioral paradigms, we determined catatonia-like symptoms and isolated executive dysfunction in both genders. This suggests that loss of myelin integrity has an impact on cortical connectivity and underlies specific defects of executive function. These observations are likewise relevant for human neuropsychiatric conditions and other myelin-related diseases.
Comprehensive glycoprofiling of oral tumours associatesN-glycosylation with lymph node metastasis and patient survival
Authors: Carnielli Carolina Moretto , Melo de Lima Morais Thayná , Malta de Sá Patroni Fábio , Prado Ribeiro Ana Carolina , Brandão Thaís Bianca , Sobroza Evandro , Matos Leandro Luongo , Kowalski Luiz Paulo , Paes Leme Adriana Franco , Kawahara Rebeca , Thaysen-Andersen Morten 
Published: November 2022

AbstractWhile altered protein glycosylation is regarded a trait of oral squamous cell carcinoma (OSCC), its heterogeneous glycoproteome and dynamics with disease progression remain unmapped. To this end, we here employ an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics applied to a valuable cohort of resected tumour tissues from OSCC patients with (n = 19) and without (n = 12) lymph node metastasis. While all tumour tissues displayed uniformN-glycome profiles suggesting relatively stable globalN-glycosylation during lymph node metastasis, glycoproteomics and advanced correlation analysis notably uncovered altered site-specificN-glycosylation and previously unknown associations with several key clinicopathological features. Importantly, focused analyses of the multi-omics data unveiled twoN-glycans and threeN-glycopeptides that were closely associated with patient survival. This study provides novel insight into the complex OSCC tissueN-glycoproteome forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glyco-markers for OSCC.TeaserDeep survey of the dynamic landscape of complex sugars in oral tumours paves a way for new prognostic disease markers.
Reducing brain kynurenic acid synthesis precludes kynurenine-induced sleep disturbances
Authors: Rentschler Katherine M. , Milosavljevic Snezana , Baratta Annalisa M. , Wright Courtney J. , Piroli Maria V. , Tentor Zachary , Valafar Homayoun , O’Reilly Christian , Pocivavsek Ana 
Published: November 2022

ABSTRACTPatients with neurocognitive disorders often battle sleep disturbances. Kynurenic acid (KYNA) is a tryptophan metabolite of the kynurenine pathway implicated in the pathology of these illnesses. Modest increases in KYNA, an antagonist at glutamatergic and cholinergic receptors, result in cognitive impairments and sleep dysfunction. We explored the hypothesis that inhibition of the KYNA synthesizing enzyme, kynurenine aminotransferase II (KAT II), may alleviate sleep disturbances. At the start of the light phase, adult male and female Wistar rats received systemic injections of either i) vehicle, ii) kynurenine (100mg/kg; i.p.), iii) the KAT II inhibitor, PF-04859989 (30 mg/kg; s.c.), or iv) PF-04859989 and kynurenine in combination. Kynurenine and KYNA levels were evaluated in the plasma and brain. Separate animals were implanted with electroencephalogram (EEG) and electromyogram (EMG) telemetry devices to record polysomnography and evaluate vigilance states wake, rapid eye movement sleep (REMS) and non-REM sleep (NREMS) following each treatment. Kynurenine challenge increased brain KYNA and resulted in reduced REMS duration, NREMS delta power and sleep spindles. PF-04859989 reduced brain KYNA formation when given prior to kynurenine, prevented disturbances in REM sleep and sleep spindles, and enhanced NREM sleep. Our findings suggest that reducing KYNA in conditions where the kynurenine pathway is activated may serve as a potential strategy for improving sleep dynamics.
Cholecystokinin from the Rhinal Cortex Facilitates Motor Skill Learning
Authors: Li Hao , Feng Jingyu , Chen Mengying , Xin Min , Chen Xi , Wang Kuan Hong , He Jufang 
Published: November 2022

AbstractCholecystokinin (CCK) is an essential modulator for neuroplasticity in sensory and emotional domains. Here, we investigated the role of CCK in motor learning using a single pellet reaching task in mice. Mice with a knockout ofcckgene (CCK-/-) or blockade of CCK-B receptor (CCKBR) showed defective motor learning ability; the success rate of retrieving reward remained at the baseline level compared to the wildtype mice with significantly increased success rate. We observed no long-term potentiation (LTP) upon high-frequency stimulation (HFS) in the motor cortex of CCK-/-mice, indicating a possible association between motor learning deficiency and neuronal plasticity in the motor cortex. In vivo calcium imaging demonstrated that the deficiency of CCK signalling disrupted the refinement of population neuronal activity in the motor cortex during motor skill training. Anatomical tracing revealed direct projections from CCK-expressing neurons in the rhinal cortex to the motor cortex. Inactivating the CCK neurons in the rhinal cortex using chemogenetic methods significantly suppressed motor learning, and intraperitoneal application of CCK4, a tetrapeptide CCK agonist, rescued the motor learning deficits of CCK-/-mice. In summary, our results suggest that CCK, which could be provided from the rhinal cortex, enables neuroplasticity in the motor cortex leading to motor skill learning.
AlphaFold predictions are valuable hypotheses, and accelerate but do not replace experimental structure determination
Authors: Terwilliger Thomas C. , Liebschner Dorothee , Croll Tristan I. , Williams Christopher J. , McCoy Airlie J. , Poon Billy K. , Afonine Pavel V. , Oeffner Robert D. , Richardson Jane S. , Read Randy J. , Adams Paul D. 
Published: November 2022

AbstractAI-based methods such as AlphaFold have revolutionized structural biology, often making it possible to predict protein structures with high accuracy. The accuracies of these predictions vary, however, and they do not include ligands, covalent modifications or other environmental factors. Here we focus on very-high-confidence parts of AlphaFold predictions, evaluating how well they can be expected to describe the structure of a protein in a particular environment. We compare predictions with experimental crystallographic maps of the same proteins for 102 crystal structures. In many cases, those parts of AlphaFold predictions that were predicted with very high confidence matched experimental maps remarkably closely. In other cases, these predictions differed from experimental maps on a global scale through distortion and domain orientation, and on a local scale in backbone and side-chain conformation. Overall, Cαatoms in very-high-confidence parts of AlphaFold predictions differed from corresponding crystal structures by a median of 0.6 Å, and about 10% of these differed by more than 2 Å, each about twice the values found for pairs of crystal structures containing the same components but determined in different space groups. We suggest considering AlphaFold predictions as exceptionally useful hypotheses. We further suggest that it is important to consider the confidence in prediction when interpreting AlphaFold predictions and to carry out experimental structure determination to verify structural details, particularly those that involve interactions not included in the prediction.
Self-assembly of CIP4 drives actin-mediated asymmetric pit-closing in clathrin-mediated endocytosis
Authors: Yu Yiming , Yoshimura Shige H. 
Published: November 2022

AbstractClathrin-mediated endocytosis is pivotal to signal transduction pathways between the extracellular environment and the intracellular space. Evidence from live-cell imaging and super-resolution microscopy of mammalian cells suggests an asymmetric distribution of actin fibres near the clathrin-coated pit, which induces asymmetric pit-closing rather than radial constriction. However, detailed molecular mechanisms of this ‘asymmetricity’ remain elusive. Herein, we used high-speed atomic force microscopy to demonstrate that CIP4, a multi-domain protein with a classic F-BAR domain and intrinsically disordered regions, is necessary for asymmetric pit-closing. Strong self-assembly of CIP4 via intrinsically disordered regions, together with stereospecific interactions with the curved membrane and actin-regulating proteins, generates a small actin-rich environment near the pit, which deforms the membrane and closes the pit. Our results provide mechanistic insights into how disordered and structured domain collaboration promotes spatio-temporal actin polymerisation near the plasma membrane.
O-GlcNAcylation promotes YTHDF1 cytosolic localization and colorectal cancer tumorigenesis
Authors: Li Jie , Ahmad Muhammad , Sang Lei , Zhan Yahui , Wang Yibo , Yan Yonghong , Liu Yue , Mi Weixiao , Lu Mei , Dai Yu , Zhang Rou , Dong Meng-Qiu , Yang Yun-Gui , Wang Xiaohui , Sun Jianwei , Li Jing 
Published: November 2022

AbstractO-linked N-acetylglucosamine (O-GlcNAc) is an emerging post-translation modification that couples metabolism with cellular signal transduction by crosstalking with phosphorylation and ubiquitination to orchestrate various biological processes. Herein we show that it modifies the N6-methyladenosine (m6A)-mRNA reader YTHDF1 and fine-tunes its nuclear translocation by the exportin protein Crm1. First we present evidence that YTHDF1 interacts with the sole O-GlcNAc transferase (OGT). Second, we verified the YTHDF1 O-GlcNAcylation sites to be Ser196/Ser197/Ser198, as described in previous numerous chemoproteomic studies. Then we constructed the O-GlcNAc-deficient YTHDF1-S196AS197FS198A (AFA) mutants, which significantly attentuated O-GlcNAc signals. Moreover, we revealed that YTHDF1 is a nucleocytoplasmic protein, whose nuclear export is mediated by Crm1. Furthermore, O-GlcNAcylation increases the cytosolic portion of YTHDF1 by enhancing binding with Crm1, thus upregulating the downstream target (e.g. c-Myc) expression. Molecular dynamics simulations suggest that O-GlcNAcylation at S197 might promote the binding between the nuclear export signal motif and Crm1 through increasing hydrogen bonding. Mouse xenograft assays further demonstrate that YTHDF1-AFA mutants decreased the colon cancer mass and size via decreasing c-Myc expression. In sum, we found that YTHDF1 is a nucleocytoplasmic protein, whose cytosolic localization is dependent on O-GlcNAc modification. We propose that the OGT-YTHDF1-c-Myc axis might underlie colorectal cancer tumorigenesis.