bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of AAA+ ATPase-mediated RuvAB–Holliday junction branch migration
Authors: Wald Jiri , Fahrenkamp Dirk , Goessweiner-Mohr Nikolaus , Lugmayr Wolfgang , Ciccarelli Luciano , Vesper Oliver , Marlovits Thomas C. 
Published: August 2022

AbstractThe Holliday junction is a key intermediate formed during DNA recombination across all kingdoms of life1. In bacteria, the Holliday junction is processed by two homo-hexameric AAA+ ATPase RuvB motors, which assemble together with the RuvA–Holliday junction complex to energize the strand-exchange reaction2. Despite its importance for chromosome maintenance, the structure and mechanism by which this complex facilitates branch migration are unknown. Here, using time-resolved cryo-electron microscopy, we obtained structures of the ATP-hydrolysing RuvAB complex in seven distinct conformational states, captured during assembly and processing of a Holliday junction. Five structures together resolve the complete nucleotide cycle and reveal the spatiotemporal relationship between ATP hydrolysis, nucleotide exchange and context-specific conformational changes in RuvB. Coordinated motions in a converter formed by DNA-disengaged RuvB subunits stimulate hydrolysis and nucleotide exchange. Immobilization of the converter enables RuvB to convert the ATP-contained energy into a lever motion, which generates the pulling force driving the branch migration. We show that RuvB motors rotate together with the DNA substrate, which, together with a progressing nucleotide cycle, forms the mechanistic basis for DNA recombination by continuous branch migration. Together, our data decipher the molecular principles of homologous recombination by the RuvAB complex, elucidate discrete and sequential transition-state intermediates for chemo-mechanical coupling of hexameric AAA+ motors and provide a blueprint for the design of state-specific compounds targeting AAA+ motors.
Phosphorylation of muramyl peptides by NAGK is required for NOD2 activation
Authors: Stafford Che A. , Gassauer Alicia-Marie , de Oliveira Mann Carina C. , Tanzer Maria C. , Fessler Evelyn , Wefers Benedikt , Nagl Dennis , Kuut Gunnar , Sulek Karolina , Vasilopoulou Catherine , Schwojer Sophia J. , Wiest Andreas , Pfautsch Marie K. , Wurst Wolfgang , Yabal Monica , Fröhlich Thomas , Mann Matthias , Gisch Nicolas , Jae Lucas T. , Hornung Veit 
Published: August 2022

AbstractBacterial cell wall components provide various unique molecular structures that are detected by pattern recognition receptors (PRRs) of the innate immune system as non-self. Most bacterial species form a cell wall that consists of peptidoglycan (PGN), a polymeric structure comprising alternating amino sugars that form strands cross-linked by short peptides. Muramyl dipeptide (MDP) has been well documented as a minimal immunogenic component of peptidoglycan1–3. MDP is sensed by the cytosolic nucleotide-binding oligomerization domain-containing protein 24 (NOD2). Upon engagement, it triggers pro-inflammatory gene expression, and this functionality is of critical importance in maintaining a healthy intestinal barrier function5. Here, using a forward genetic screen to identify factors required for MDP detection, we identified N-acetylglucosamine kinase (NAGK) as being essential for the immunostimulatory activity of MDP. NAGK is broadly expressed in immune cells and has previously been described to contribute to the hexosamine biosynthetic salvage pathway6. Mechanistically, NAGK functions upstream of NOD2 by directly phosphorylating the N-acetylmuramic acid moiety of MDP at the hydroxyl group of its C6 position, yielding 6-O-phospho-MDP. NAGK-phosphorylated MDP—but not unmodified MDP—constitutes an agonist for NOD2. Macrophages from mice deficient in NAGK are completely deficient in MDP sensing. These results reveal a link between amino sugar metabolism and innate immunity to bacterial cell walls.
RASA2 ablation in T cells boosts antigen sensitivity and long-term function
Authors: Carnevale Julia , Shifrut Eric , Kale Nupura , Nyberg William A. , Blaeschke Franziska , Chen Yan Yi , Li Zhongmei , Bapat Sagar P. , Diolaiti Morgan E. , O’Leary Patrick , Vedova Shane , Belk Julia , Daniel Bence , Roth Theodore L. , Bachl Stefanie , Anido Alejandro Allo , Prinzing Brooke , Ibañez-Vega Jorge , Lange Shannon , Haydar Dalia , Luetke-Eversloh Marie , Born-Bony Maelys , Hegde Bindu , Kogan Scott , Feuchtinger Tobias , Okada Hideho , Satpathy Ansuman T. , Shannon Kevin , Gottschalk Stephen , Eyquem Justin , Krenciute Giedre , Ashworth Alan , Marson Alexander 
Published: August 2022

AbstractThe efficacy of adoptive T cell therapies for cancer treatment can be limited by suppressive signals from both extrinsic factors and intrinsic inhibitory checkpoints1,2. Targeted gene editing has the potential to overcome these limitations and enhance T cell therapeutic function3–10. Here we performed multiple genome-wide CRISPR knock-out screens under different immunosuppressive conditions to identify genes that can be targeted to prevent T cell dysfunction. These screens converged on RASA2, a RAS GTPase-activating protein (RasGAP) that we identify as a signalling checkpoint in human T cells, which is downregulated upon acute T cell receptor stimulation and can increase gradually with chronic antigen exposure. RASA2 ablation enhanced MAPK signalling and chimeric antigen receptor (CAR) T cell cytolytic activity in response to target antigen. Repeated tumour antigen stimulations in vitro revealed that RASA2-deficient T cells show increased activation, cytokine production and metabolic activity compared with control cells, and show a marked advantage in persistent cancer cell killing. RASA2-knockout CAR T cells had a competitive fitness advantage over control cells in the bone marrow in a mouse model of leukaemia. Ablation of RASA2 in multiple preclinical models of T cell receptor and CAR T cell therapies prolonged survival in mice xenografted with either liquid or solid tumours. Together, our findings highlight RASA2 as a promising target to enhance both persistence and effector function in T cell therapies for cancer treatment.
Immune modulation by molecularly targeted photothermal ablation in a mouse model of advanced hepatocellular carcinoma and cirrhosis
Authors: Muñoz Nina M. , Dupuis Crystal , Williams Malea , Dixon Katherine , McWatters Amanda , Zhang Jie , Pavuluri Swathi , Rao Arvind , Duda Dan G. , Kaseb Ahmed , Sheth Rahul A. 
Published: August 2022

AbstractImmunotherapy is a promising new treatment approach for hepatocellular carcinoma (HCC), but there are numerous barriers to immunotherapy in HCC, including an immunosuppressive microenvironment and the “immunotolerance” of the liver. Hyperthermia treatment modalities are standard of care for early stage HCC, and hyperthermia is known to have immunomodulatory effects. We have developed a molecularly targeted photothermal ablation (MTPA) technology that provides thermally tunable, tumor-specific heat generation. The purpose of this study was to evaluate the morphologic and immunologic effects of MTPA in an immunotherapy-resistant syngeneic mouse model of HCC in a background of toxin-induced cirrhosis. We found that the anatomic, cellular, and molecular features of this model recapitulate the characteristics of advanced human HCC. MTPA as a monotherapy and in combination with immune checkpoint therapy significantly increased intratumoral CD3+ and activated CD8+ T cells while decreasing regulatory T cells relative to control or immune checkpoint therapy alone based on immunohistochemistry, flow cytometry, and single cell RNA sequencing data. Furthermore, we identified evidence of MTPA’s influence on systemic tumor immunity, with suppression of remote tumor growth following treatment of orthotopic tumors. The results of this study suggest that tumor-specific hyperthermia may help overcome resistance mechanisms to immunotherapy in advanced HCC.
New quantum physics, solving puzzles of Wheeler’s delayed choice and a particle’s passing N slits simultaneously and quantum oscillator in experiments
Authors: Huang Changyu , Huang Yong-Chang , Nie Yi-You 
Published: August 2022

AbstractThis paper discovers new quantum physics, and gives solutions to puzzles of Wheeler’s delayed choice and a particle’s passing many slits simultaneously by exact quantum physics expressions. We further show new quantum control, new quantum oscillation, new quantum control experiments and new quantum oscillator being able to be installed in quantum communication network etc. We discover that the ability of a photon to hit electrons out in photoelectric effect is complementarily equivalent to the ability of wave of a photon to simultaneously pass through many slits in wave-particle duality. Objective criterion for distinguishing classical and quantum particles is found, and this paper gives applicable realm of quantum theories and new quantum physics expressions of wave-particle duality. All these studies above should be classified as classical and quantum particles, then classical particle and quantum particle wave cannot and can pass many slits, respectively. This paper discovers wave-particle duality’s origin of displaying both wave property from plane wave part of the general Fourier expansion and particle property from the general Fourier expansion coefficients with the particle’s global property and spins etc. We give the superposition state representation of wave-particle duality, further find the collapse of the duality superposition state to wave or particle state. The collapsed wave or particle state is related to the measure of wave or particle property. Then, we explain why sometimes it's a wave or a particle. Our achieved results are truly tested, and we discover new measured attractive state and quantum wave collapse velocity expression.
Assessing the expansion of the Cambrian Agronomic Revolution into fan-delta environments
Authors: Ichaso Andrei , Buatois Luis A. , Mángano M. Gabriela , Thomas Patty , Marion Don 
Published: August 2022

AbstractThe intensity, extent, and ecosystem-level impact of bioturbation (i.e. Agronomic Revolution) at the dawn of the Phanerozoic is a hotly debated issue. Middle Cambrian fan-delta deposits in southwestern Saskatchewan provide insights into the paleoenvironmental extent of the Agronomic Revolution into marginal-marine environments. The studied deposits reveal that several environmental stressors had direct impact on trace-fossil distribution and bioturbation intensities in Cambrian fan deltas. Basal and proximal subaerial deposits are characterized by very coarse grain size and absence of bioturbation. Mid-fan and fan-toe deposits were formed under subaqueous conditions and are characterized by rapid bioturbation events in between sedimentation episodes when environmental stressors were ameliorated, providing evidence of a significant landward expansion of the Agronomic Revolution. Transgressive marine deposits accumulated after the abandonment of the fan-delta system display high levels of bioturbation intensity, reflecting stable environmental conditions that favored endobenthic colonization. The presence of intense bioturbation in both subaqueous fan delta and transgressive deposits provides further support to the view that Cambrian levels of biogenic mixing were high, provided that stable environmental conditions were reached. Our study underscores the importance of evaluating sedimentary facies changes to assess the impact of environmental factors prior to making evolutionary inferences.
Gallic and ascorbic acids supplementation alleviate cognitive deficits and neuropathological damage exerted by cadmium chloride in Wistar rats
Authors: Adebiyi Olamide , Adigun Kabirat , David-Odewumi Praise , Akindele Uthman , Olayemi Funsho 
Published: August 2022

AbstractCadmium is a highly neurotoxic heavy metal that interferes with DNA repair mechanisms via generation of reactive oxygen species. The potentials of polyphenols and antioxidants as effective protective agents following heavy metal-induced neurotoxicity are emerging. We therefore explored the neuroprotective potentials of gallic and ascorbic acids in CdCl2-induced neurotoxicity. Seventy-two Wistar rats were divided into six groups. Group A received distilled water, B: 3 mg/kg CdCl2, C: 3 mg/kg CdCl2 + 20 mg/kg gallic acid (GA), D: 3 mg/kg CdCl2 + 10 mg/kg ascorbic acid (AA), E: 20 mg/kg GA and F: 10 mg/kg AA orally for 21 days. Depression, anxiety, locomotion, learning and memory were assessed using a battery of tests. Neuronal structure and myelin expression were assessed with histological staining and immunofluorescence. The Morris Water Maze test revealed significant increase in escape latency in CdCl2group relative to rats concurrently treated with GA or AA. Similarly, time spent in the target quadrant was reduced significantly in CdCl2group relative to other groups. Concomitant administration of gallic acid led to significant reduction in the durations of immobility and freezing that were elevated in CdCl2group during forced swim and open field tests respectively. Furthermore, GA and AA restored myelin integrity and neuronal loss observed in the CdCl2group. We conclude that gallic and ascorbic acids enhance learning and memory, decrease anxiety and depressive-like behavior in CdCl2-induced neurotoxicity with accompanying myelin-protective ability.
Spatiotemporal evolution of seismicity during the cyclic operation of the Hutubi underground gas storage, Xinjiang, China
Authors: Zhang Bo , Wang Baoshan , Wei Bin , Wu Zhide , Wu Ni-Er , Lu Renqi , Ji Zhanbo , Hou Jinxin , Li Lu 
Published: August 2022

AbstractUnderground gas storages (UGSs) are important large-scale industrial facilities used to bridge the gap between natural gas consumption and supply. The cyclic operation of the UGS may alter the subsurface stresses and local seismicity. We examined seismicity around the Hutubi UGS from 2011 to 2019 using the matched filter technique (MFT) and double-difference location methods. More than 1300 earthquakes were detected with seismicity around the UGS showing a remarkable increase since the start of its operation and showing a clear correlation to seasonal gas production. About 684 detected earthquakes were located, most of them occurred within 6 km of the reservoir. The events can be grouped into two clusters. Both clusters initiated around the gas pressure boundary. The first cluster extinct after the first injection period. While the second cluster diffused upward along a pre-existing fault. We speculate that strain localization caused by non-uniform gas injection contributes to the initiation of seismicity clusters around the UGS, and the trapped crude oil/gas played an important role in the migration of the second surge. The revealed seismicity pattern contributes to a better understanding of the mechanism of induced seismic events and emphasizes the importance of seismic monitoring in the UGS region.
Video calls did not reduce PTSD symptoms in relatives during restricted ICU visits in the COVID-19 pandemic
Authors: Zante Bjoern , Erne Katja , Jeitziner Marie-Madlen 
Published: August 2022

AbstractTo help reduce the spread of the SARS-CoV-2 virus during the COVID-19 pandemic, ICU visits were banned or restricted. Therefore, family-centered care as usually practiced was not feasible Video calls were recommended to meet relatives’ needs. The aim of this study was to investigate the effect of video calls on symptoms of post-traumatic stress disorder (PTSD) in relatives of ICU patients. This single-center study was performed during the first wave (15.03.2020‒30.04.2020; visits banned) and the second wave (01.10.20‒08.02.21: visits restricted) of the COVID-19 pandemic. The Impact of Event Scale-Revised (IES-R) was used to assess PTSD symptoms and an adapted version of the Family Satisfaction in the Intensive Care Unit 24-Item-Revised questionnaire (aFS-ICU 24R) to assess family satisfaction 3 months after ICU stay. The primary outcome was the difference in IES-R score at 3 months between the video call group (VCG) and the standard care group (SCG, no video calls). In addition, inductive content analysis of relatives’ comments regarding their satisfaction with decision-making and ICU care was performed. Fifty-two relatives (VCG: n = 26, SCG: n = 26) were included in this study. No significant difference in IES-R scores was observed between the VCG and the SCG (49.52 ± 13.41 vs. 47.46 ± 10.43, p = 0.54). During the ICU stay (mean 12 days, range 5.25‒18.75 days), the members of the VCG made a median of 3 (IQR 1‒10.75) video calls. No difference between the groups was found for conventional telephone calls during the same period (VCG: 9 calls, IQR 3.75‒18.1; SCG: 5 calls, IQR 3‒9; p = 0.12). The aFS-ICU 24R scores were high for both groups: 38 (IQR 37‒40) in the VCG and 40 (IQR 37‒40: p = 0.24) in the SCG. Video calls appeared largely ineffective in reducing PTSD symptoms or improving satisfaction among relatives affected by banning/restriction of ICU visits during the COVID-19 pandemic. Further investigations are needed to acquire more data on the factors involved in PTSD symptoms experienced by relatives of ICU patients during the COVID-19 pandemic.
Cosine similarity measures between q-rung orthopair linguistic sets and their application to group decision making problems
Authors: Ali Jawad , Naeem Muhammad 
Published: August 2022

AbstractThe q-rung orthopair linguistic set (q-ROLS), a combined version of linguistic term sets and q-rung orthopair fuzzy set, is an efficient mathematical tool to accomplish the imprecise information while solving the decision-making problems. Under this environment, we propose additional operations and relations to deal with the decision information, and some properties are well proved. Furthermore, we propound some cosine similarity measures and weighted cosine similarity measures for q-ROLSs based on the traditional cosine similarity measures with a brief study of related properties. In the proposed similarity measures, various linguistic scale functions are utilized in order to take into account the semantics of linguistic terms. Besides this, we employ the stated q-rung orthopair linguistic similarity measures to multi-criteria group decision making problems, in which the weights of DMs are delineated by the projection of individual decisions on the ideal decision results. At last, a numerical example is used to demonstrate the practicality of the suggested technique, and its efficacy is validated by comparison with prevailing techniques. The suggested method’s sensitivity and stability analyses are also provided.
Tumor microbiome diversity influences papillary thyroid cancer invasion
Authors: Yuan Lijuan , Yang Ping , Wei Gang , Hu Xi’e , Chen Songhao , Lu Jianguo , Yang Lin , He Xianli , Bao Guoqiang 
Published: August 2022

AbstractPapillary thyroid carcinoma (PTC) has a high incidence, and its proper treatment remains challenging. Therefore, identifying PTC progression markers is essential. Here, using 16S RNA sequences, we analyzed the PTC intratumor microbiome and its role in tumor progression. Substantial microbial abundance was detected in PTC from all patients. The tumor bacterial diversity in patients with advanced lesions (T3/T4) was significantly higher than that in patients with relatively mild lesions (T1/T2). Importantly, we identified signatures of eight tumor bacterial taxa highly predictive of PTC invasion status. Hence, microbial host factors—independent of the genomic composition of the tumor—may determine tumor behaviors and patient outcomes. Furthermore, the correlation between specific bacterial genus and thyroid hormones or autoimmune thyroid disease-related antibodies may indicate the potential contribution of the microbiome in the relationship between autoimmune thyroid disease or irregular thyroid function and PTC progression, intervention of which might therefore be worth exploring for advancing oncology care.
Spelling Errors in French Elementary School Students: A Linguistic Analysis
Authors: Joye Nelly , Broc Lucie , Marshall Chloë Ruth , Dockrell Julie Elizabeth 
Published: August 2022

Purpose:
This study offers the first description of misspellings across elementary school using the Phonological, Orthographic and Morphological Assessment of Spelling (POMAS), a linguistic framework based on Triple Word Form theory, adapted for French (POMAS-FR). It aims to test the “universality” of POMAS and its suitability to track development in French spelling.

Method:
One hundred ninety-four typically developing French children (Grades 1–5) produced a written narrative and words-to-dictation. These were analyzed for productivity and accuracy. Misspellings were then analyzed using POMAS-FR.

Results:
Productivity and accuracy were better in the later grades. POMAS-FR provided a novel framework for tracking error types in our French sample. The data showed a linear trend for text production, whereby the proportion of phonological errors decreased rapidly in the early grades, while orthographic errors decreased and morphological errors increased throughout elementary school. Words-to-dictation showed a more stable pattern, with a steady decrease in phonological errors, and a stable proportion of orthographic and morphological errors. The specific error types found within each linguistic category are described for both tasks.

Conclusions:
The POMAS-FR allowed for the characterization of linguistic knowledge involved in learning to spell French across elementary school. Interplays between different types of linguistic knowledge were evident at all grades. In comparison with other writing systems, French text spelling competence relied heavily on morphological knowledge. These results suggest POMAS may be applied to other orthographic systems. It also highlights the importance of task and word selection for the qualitative evaluation of spelling.

Supplemental Material:

https://doi.org/10.23641/asha.20520774
Warship formation extraction and recognition based on density‐based spatial clustering of applications with noise and improved convolutional neural network
Authors: He Haotian , Wu Ling , Hu Xianjun 
Published: August 2022

AbstractFormation recognition is a significant focus of maritime target recognition. Automatic formation extraction and recognition facilitate autonomous decision‐making. However, few studies have explored formation extraction prior to recognition. This paper introduces a density‐based spatial clustering of applications with noise (DBSCAN) method based on Gaussian kernel to extract formation targets. On this basis, a depthwise separable convolutional neural network (DSCNN) method is proposed for formation recognition. A track simulation system is established to form a track dataset containing three different proportions of clutter, and the formation extraction method is examined using track dataset. Subsequently, the image dataset with eight different types of formation is formulated, on the basis of various detection errors, the DSCNN method for formation recognition is compared with several typical deep learning methods. As exposed in experimental results, the DBSCAN method based on Gaussian kernel can guarantee accurate extraction of formation targets subject to different proportions of clutter. Hence, it is greatly robust and capable of effective formation extraction. Under different radar detection errors, the formation recognition accuracy of DSCNN is 91.5%–99.5%, which achieves performance improvement by up to 12.5% compared with other deep learning methods. The combination of DBSCAN and DSCNN can well realise formation extraction and recognition with different proportions of clutter in tracks and various radar detection errors.