bluuebunny/crossref_metadata_2025_split huggingface dataset:
ROS homeostasis mediated by MPK4 and SUMM2 determines synergid cell death
Authors: Völz Ronny , Harris William , Hirt Heribert , Lee Yong-Hwan 
Published: April 2022

AbstractSexual plant reproduction depends on the attraction of sperm-cell delivering pollen tubes (PT) by two synergids, followed by their programmed cell death (PCD) in Arabidopsis. Disruption of the mitogen-activated protein kinase 4 (MPK4) by pathogenic effectors activates the resistance protein (R) SUMM2-mediated immunity and cell death. Here we show that synergid preservation and reactive oxygen species (ROS) homeostasis are intimately linked and maintained by MPK4. In mpk4, ROS levels are increased and synergids prematurely undergo PCD before PT-reception. However, ROS scavengers and the disruption of SUMM2, in mpk4, restore ROS homeostasis, synergid maintenance and PT perception, demonstrating that the guardian of MPK4, SUMM2, triggers synergid-PCD. In mpk4/summ2, PTs show a feronia-like overgrowth phenotype. Our results show that immunity-associated PCD and synergid cell death during plant reproduction are regulated by MPK4 underscoring an underlying molecular mechanism for the suppression of plant reproduction during systemic R-mediated immunity.
Chirality transfer from a 3D macro shape to the molecular level by controlling asymmetric secondary flows
Authors: Sevim Semih , Sorrenti Alessandro , Vale João Pedro , El-Hachemi Zoubir , Pané Salvador , Flouris Andreas D. , Mayor Tiago Sotto , Puigmartí-Luis Josep 
Published: April 2022

AbstractHomochirality is a fundamental feature of living systems, and its origin is still an unsolved mystery. Previous investigations showed that external physical forces can bias a spontaneous symmetry breaking process towards deterministic enantioselection. But can the macroscopic shape of a reactor play a role in chiral symmetry breaking processes? Here we show an example of chirality transfer from the chiral shape of a 3D helical channel to the chirality of supramolecular aggregates, with the handedness of the helical channel dictating the direction of enantioselection in the assembly of an achiral molecule. By combining numerical simulations of fluid flow and mass transport with experimental data, we demonstrated that the chiral information is transferred top-down thanks to the interplay between the hydrodynamics of asymmetric secondary flows and the precise spatiotemporal control of reagent concentration fronts. This result shows the possibility of controlling enantioselectively molecular processes at the nanometer scale by modulating the geometry and the operating conditions of fluidic reactors.
Adverse biobehavioral effects in infants resulting from pregnant rhesus macaques’ exposure to wildfire smoke
Authors: Capitanio John P. , Del Rosso Laura A. , Gee Nancy , Lasley Bill L. 
Published: April 2022

AbstractAs wildfires across the world increase in number, size, and intensity, exposure to wildfire smoke (WFS) is a growing health problem. To date, however, little is known for any species on what might be the behavioral or physiological consequences of prenatal exposure to WFS. Here we show that infant rhesus monkeys exposed to WFS in the first third of gestation (n = 52) from the Camp Fire (California, November, 2018) show greater inflammation, blunted cortisol, more passive behavior, and memory impairment compared to animals conceived after smoke had dissipated (n = 37). Parallel analyses, performed on a historical control cohort (n = 2490), did not support the alternative hypothesis that conception timing alone could explain the results. We conclude that WFS may have a teratogenic effect on the developing fetus and speculate on mechanisms by which WFS might affect neural development.
Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates
Authors: Rutkai Ibolya , Mayer Meredith G. , Hellmers Linh M. , Ning Bo , Huang Zhen , Monjure Christopher J. , Coyne Carol , Silvestri Rachel , Golden Nadia , Hensley Krystle , Chandler Kristin , Lehmicke Gabrielle , Bix Gregory J. , Maness Nicholas J. , Russell-Lodrigue Kasi , Hu Tony Y. , Roy Chad J. , Blair Robert V. , Bohm Rudolf , Doyle-Meyers Lara A. , Rappaport Jay , Fischer Tracy 
Published: April 2022

AbstractNeurological manifestations are a significant complication of coronavirus disease (COVID-19), but underlying mechanisms aren’t well understood. The development of animal models that recapitulate the neuropathological findings of autopsied brain tissue from patients who died from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are critical for elucidating the neuropathogenesis of infection and disease. Here, we show neuroinflammation, microhemorrhages, brain hypoxia, and neuropathology that is consistent with hypoxic-ischemic injury in SARS-CoV-2 infected non-human primates (NHPs), including evidence of neuron degeneration and apoptosis. Importantly, this is seen among infected animals that do not develop severe respiratory disease, which may provide insight into neurological symptoms associated with “long COVID”. Sparse virus is detected in brain endothelial cells but does not associate with the severity of central nervous system (CNS) injury. We anticipate our findings will advance our current understanding of the neuropathogenesis of SARS-CoV-2 infection and demonstrate SARS-CoV-2 infected NHPs are a highly relevant animal model for investigating COVID-19 neuropathogenesis among human subjects.
Unprecedented decline of Arctic sea ice outflow in 2018
Authors: Sumata Hiroshi , de Steur Laura , Gerland Sebastian , Divine Dmitry V. , Pavlova Olga 
Published: April 2022

AbstractFram Strait is the major gateway connecting the Arctic Ocean and North Atlantic Ocean, where nearly 90% of the sea ice export from the Arctic Ocean takes place. The exported sea ice is a large source of freshwater to the Nordic Seas and Subpolar North Atlantic, thereby preconditioning European climate and deep water formation in the North Atlantic Ocean. Here we show that in 2018, the ice export through Fram Strait showed an unprecedented decline since the early 1990s. The 2018 ice export was reduced to less than 40% relative to that between 2000 and 2017. The minimum export is attributed to regional sea ice-ocean processes driven by an anomalous atmospheric circulation over the Atlantic sector of the Arctic. The result indicates that a drastic change of the Arctic sea ice outflow and its environmental consequences happen not only through Arctic-wide ice thinning, but also by regional scale atmospheric anomalies.
PI3Kγ stimulates a high molecular weight form of myosin light chain kinase to promote myeloid cell adhesion and tumor inflammation
Authors: Schmid Michael C. , Kang Sang Won , Chen Hui , Paradise Marc , Ghebremedhin Anghesom , Kaneda Megan M. , Chin Shao-Ming , Do Anh , Watterson D. Martin , Varner Judith A. 
Published: April 2022

AbstractMyeloid cells play key roles in cancer immune suppression and tumor progression. In response to tumor derived factors, circulating monocytes and granulocytes extravasate into the tumor parenchyma where they stimulate angiogenesis, immune suppression and tumor progression. Chemokines, cytokines and interleukins stimulate PI3Kγ-mediated Rap1 activation, leading to conformational changes in integrin α4β1 that promote myeloid cell extravasation and tumor inflammation Here we show that PI3Kγ activates a high molecular weight form of myosin light chain kinase, MLCK210, that promotes myosin-dependent Rap1 GTP loading, leading to integrin α4β1 activation. Genetic or pharmacological inhibition of MLCK210 suppresses integrin α4β1 activation, as well as tumor inflammation and progression. These results demonstrate a critical role for myeloid cell MLCK210 in tumor inflammation and serve as basis for the development of alternative approaches to develop immune oncology therapeutics.
Processing of visual and non-visual naturalistic spatial information in the "parahippocampal place area"
Authors: Häusler Christian O. , Eickhoff Simon B. , Hanke Michael 
Published: April 2022

AbstractThe “parahippocampal place area” (PPA) in the human ventral visual stream exhibits increased hemodynamic activity correlated with the perception of landscape photos compared to faces or objects. Here, we investigate the perception of scene-related, spatial information embedded in two naturalistic stimuli. The same 14 participants were watching a Hollywood movie and listening to its audio-description as part of the open-data resource studyforrest.org. We model hemodynamic activity based on annotations of selected stimulus features, and compare results to a block-design visual localizer. On a group level, increased activation correlating with visual spatial information occurring in the movie is overlapping with a traditionally localized PPA. Activation correlating with semantic spatial information occurring in the audio-description is more restricted to the anterior PPA. On an individual level, we find significant bilateral activity in the PPA of nine individuals and unilateral activity in one individual. Results suggest that activation in the PPA generalizes to spatial information embedded in a movie and an auditory narrative, and may call for considering a functional subdivision of the PPA.
Characterization of an engineered mucus microenvironment for in vitro modeling of host–microbe interactions
Authors: Huang Andy J. , O’Brien Courtney L. , Dawe Nicholas , Tahir Anas , Scott Alison J. , Leung Brendan M. 
Published: April 2022

AbstractThe human mucus layer plays a vital role in maintaining health by providing a physical barrier to pathogens. This biological hydrogel also provides the microenvironment for commensal bacteria. Common models used to study host–microbe interactions include gnotobiotic animals or mammalian–microbial co-culture platforms. Many of the current in vitro models lack a sufficient mucus layer to host these interactions. In this study, we engineered a mucus-like hydrogel Consisting of a mixed alginate-mucin (ALG-MUC) hydrogel network by using low concentration calcium chloride (CaCl2) as crosslinker. We demonstrated that the incorporation of ALG-MUC hydrogels into an aqueous two-phase system (ATPS) co-culture platform can support the growth of a mammalian monolayer and pathogenic bacteria. The ALG-MUC hydrogels displayed selective diffusivity against macromolecules and stability with ATPS microbial patterning. Additionally, we showed that the presence of mucin within hydrogels contributed to an increase in antimicrobial resistance in ATPS patterned microbial colonies. By using common laboratory chemicals to generate a mammalian–microbial co-culture system containing a representative mucus microenvironment, this model can be readily adopted by typical life science laboratories to study host–microbe interaction and drug discovery.
Ceramides and phospholipids in plasma extracellular vesicles are associated with high risk of major cardiovascular events after carotid endarterectomy
Authors: Timmerman Nathalie , Waissi Farahnaz , Dekker Mirthe , de Borst Gert J. , van Bennekom Joelle , de Winter Robbert J. , Hilvo Mika , Jylhä Antti , Pasterkamp Gerard , de Kleijn Dominique P. V. , Laaksonen Reijo 
Published: April 2022

AbstractCeramides and phosphatidylcholines (PCs) are bioactive lipids and lipid bilayer membrane components. Distinct ceramides/PCs (ratios) predict cardiovascular outcome in patients with coronary artery disease. Extracellular vesicles (EVs) are proposed biomarkers for cardiovascular disease and contain ceramides/PCs. Ceramides/PCs have not been studied in patients undergoing carotid endarterectomy (CEA) nor in EVs. We therefore investigated whether levels of ceramides/PCs in plasma and EVs are associated with postoperative risk of major adverse cardiovascular events (MACE) following CEA. In 873 patients undergoing CEA of the Athero-Express biobank, we quantitatively measured seven ceramides/PCs in preoperative blood samples: Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), Cer(d18:1/24:1), PC(14:0/22:6), PC(16:0/16:0) and PC(16:0/22:5) in plasma and two plasma EV-subfractions (LDL and TEX). We analyzed the association of ceramides, PCs and their predefined ratios with the three-year postoperative risk of MACE (including stroke, myocardial infarction and cardiovascular death). A total of 138 patients (16%) developed MACE during the three-year follow-up. In the LDL-EV subfraction, higher levels of Cer(d18:1/24:1) and Cer(d18:1/16:0)/PC(16:0/22:5) ratio were significantly associated with an increased risk of MACE (adjusted HR per SD [95% CI] 1.24 [1.01–1.53] and 1.26 [1.04–1.52], respectively). In the TEX-EV subfraction, three ratios Cer(d18:1/16:0)/Cer(d18:1/24:0), Cer(d18:1/18:0)/Cer(d18:1/24:0) and Cer(d18:1/24:1)/Cer(d18:1/24:0) were positively associated with MACE (adjusted HR per SD 1.34 [1.06–1.70], 1.24 [1.01–1.51] and 1.31 [1.08–1.58], respectively). In conclusion, distinct ceramides and PCs in plasma EVs determined in preoperative blood were independently associated with an increased 3-year risk of MACE after CEA. These lipids are therefore potential markers to identify high-risk CEA patients qualifying for secondary preventive add-on therapy.
Chronic pancreatitis and cancer risk in a matched cohort study using national claims data in South Korea
Authors: Han Minji , Tran Thi Phuong Thao , Oh Jin-Kyoung 
Published: April 2022

AbstractThis study aimed to examine the association between chronic pancreatitis (CP) and cancer incidence and mortality among the Korean population. Based on a cancer-free cohort of 8,317,616 individuals between 2002 and 2010, a matched cohort study was conducted, including 10,899 patients with CP, matched for sex and age with 32,697 individuals without CP. The case and control groups were followed up until the date of onset of cancer or death or the end of follow-up date (December 31, 2018). Cox proportional hazards regression was performed to assess the risk of cancer incidence and mortality. Compared to the control group, patients with CP had a higher risk of all cancers with a hazard ratio (HR) of 1.2 [95% confidence interval (CI) 1.1–1.3]. CP was associated with an increased risk of esophageal cancer (HR 3.9, 95% CI 1.8–8.5) and pancreatic cancer (HR 3.9, 95% CI 2.7–5.5) and a decreased risk of colorectal cancer (HR 0.7, 95% CI 0.5–0.9). Regarding cancer mortality, patients with CP had a 1.2-fold risk of all cancer mortality (95% CI 1.1–1.4), compared with the control group. Patients with CP had a higher risk of death from esophageal cancer (HR 3.5, 95% CI 1.5–8.0) and pancreatic cancer (HR 3.3, 95% CI 2.3–4.7) but had a lower risk of death due to stomach cancer (HR 0.4, 95% CI 0.2–0.8). Patients with CP had a higher risk for both incidence and mortality of all cancer types, especially pancreatic and esophageal cancers, compared with the sex- and age-matched control group.
Anatomical considerations for appropriate mini-plate positioning in open-door laminoplasty to avoid plate impingement and screw facet violation
Authors: Yang Jae Jun , Park Sehan 
Published: April 2022

AbstractThis study aimed to describe a safe zone for mini-plate positioning that can avoid instrument-related complications in laminoplasty. Fifty-one patients who underwent laminoplasty and were followed up for at least 1 year were retrospectively reviewed. The posterior surface length and inferior pole angle of the lateral mass were measured at each level using computed tomography. The safe zone was defined based on these measurements. Incidences of screw facet violation and plate impingement were recorded. Patient-reported outcome measures were compared between the appropriate position (AP) and inappropriate position (IP) groups. Among 40 patients included, 15 (37.5%) had inappropriate plate positioning, causing screw facet violation or plate impingement, which more commonly occurred at distal (C5, C6) and proximal (C3, C4) levels, respectively. Lateral mass posterior surface length was shorter at the proximal levels, and the inferior pole angle of the lateral mass was smaller at the distal levels, signifying that the lateral mass became thin and long at the distal levels. Patient-reported outcome measures were not significantly different between the two groups. However, cervical range of motion at the final follow-up was significantly less in the IP group (p = 0.01). The suggested safe zone demonstrates that inserting the mini-plate with plate-to-lateral mass inferior pole distances of 4–5 mm and 5–6 mm at the C3–C5 and C6–C7 levels, respectively, would avoid instrument-related complications. The risk of plate impingement was higher at the proximal level, whereas the risk of screw facet violation was higher at the distal level in open-door cervical laminoplasty. These risks coincide with anatomical differences at each level. Despite inappropriate positioning of the mini-plate, clinical outcomes were not adversely affected.
XGB-DrugPred: computational prediction of druggable proteins using eXtreme gradient boosting and optimized features set
Authors: Sikander Rahu , Ghulam Ali , Ali Farman 
Published: April 2022

AbstractAccurate identification of drug-targets in human body has great significance for designing novel drugs. Compared with traditional experimental methods, prediction of drug-targets via machine learning algorithms has enhanced the attention of many researchers due to fast and accurate prediction. In this study, we propose a machine learning-based method, namely XGB-DrugPred for accurate prediction of druggable proteins. The features from primary protein sequences are extracted by group dipeptide composition, reduced amino acid alphabet, and novel encoder pseudo amino acid composition segmentation. To select the best feature set, eXtreme Gradient Boosting-recursive feature elimination is implemented. The best feature set is provided to eXtreme Gradient Boosting (XGB), Random Forest, and Extremely Randomized Tree classifiers for model training and prediction. The performance of these classifiers is evaluated by tenfold cross-validation. The empirical results show that XGB-based predictor achieves the best results compared with other classifiers and existing methods in the literature.
Intelligent escalator passenger safety management
Authors: Osipov Vasily , Zhukova Nataly , Subbotin Alexey , Glebovskiy Petr , Evnevich Elena 
Published: April 2022

AbstractThis article addresses an approach to intelligent safety control of passengers on escalators. The aim is to improve the accuracy of detecting threatening situations on escalators in the subway to make decisions to prevent threats and eliminate the consequences. The novelty of the approach lies in the complex processing of information from three types of sources (video, audio, sensors) using machine learning methods and recurrent neural networks with controlled elements. The conditions and indicators of safety assurance efficiency are clarified. New methods and algorithms for managing the safety of passengers on escalators are proposed. The architecture of a promising safety software system is developed, and implementation of its components for cloud and fog computing environments is provided. Modeling results confirm the capabilities and advantages of the proposed technological solutions for enhancing the safety of escalator passengers, efficiency of control decision making, and system usability. Due to the proposed solutions, it has become possible to increase the speed of identifying situations 3.5 times and increase the accuracy of their determination by 26%. The efficiency of decision making has increased by almost 30%.
Molecular mechanisms of Huanglian jiedu decoction on ulcerative colitis based on network pharmacology and molecular docking
Authors: Yang Jing , Tang Chaotao , Jin Ruiri , Liu Bixia , Wang Peng , Chen Youxiang , Zeng Chunyan 
Published: April 2022

AbstractHuanglian jiedu decoction (HLJDD) is a heat-clearing and detoxifying agent composed of four kinds of Chinese herbal medicine. Previous studies have shown that HLJDD can improve the inflammatory response of ulcerative colitis (UC) and maintain intestinal barrier function. However, its molecular mechanism is not completely clear. In this study, we verified the bioactive components (BCI) and potential targets of HLJDD in the treatment of UC using network pharmacology and molecular docking, and constructed the pharmacological network and PPI network. Then the core genes were enriched by GO and KEGG. Finally, the bioactive components were docked with the key targets to verify the binding ability between them. A total of 54 active components related to UC were identified. Ten genes are very important to the PPI network. Functional analysis showed that these target genes were mainly involved in the regulation of cell response to different stimuli, IL-17 signal pathway and TNF signal pathway. The results of molecular docking showed that the active components of HLJDD had a good binding ability with the Hub gene. This study systematically elucidates the “multi-component, multi-target, multi-pathway” mechanism of anti-UC with HLJDD for the first time, suggesting that HLJDD or its active components may be candidate drugs for the treatment of ulcerative colitis.
Infection with the hepatitis C virus causes viral genotype-specific differences in cholesterol metabolism and hepatic steatosis
Authors: Sheridan David A. , Shawa Isaac Thom , Thomas E. Louise , Felmlee Daniel J. , Bridge Simon H. , Neely Dermot , Cobbold Jeremy F. , Holmes Elaine , Bassendine Margaret F. , Taylor-Robinson Simon D. 
Published: April 2022

AbstractLipids play essential roles in the hepatitis C virus (HCV) life cycle and patients with chronic HCV infection display disordered lipid metabolism which resolves following successful anti-viral therapy. It has been proposed that HCV genotype 3 (HCV-G3) infection is an independent risk factor for hepatocellular carcinoma and evidence suggests lipogenic proteins are involved in hepatocarcinogenesis. We aimed to characterise variation in host lipid metabolism between participants chronically infected with HCV genotype 1 (HCV-G1) and HCV-G3 to identify likely genotype-specific differences in lipid metabolism. We combined several lipidomic approaches: analysis was performed between participants infected with HCV-G1 and HCV-G3, both in the fasting and non-fasting states, and after sustained virological response (SVR) to treatment. Sera were obtained from 112 fasting patients (25% with cirrhosis). Serum lipids were measured using standard enzymatic methods. Lathosterol and desmosterol were measured by gas-chromatography mass spectrometry (MS). For further metabolic insight on lipid metabolism, ultra-performance liquid chromatography MS was performed on all samples. A subgroup of 13 participants had whole body fat distribution determined using in vivo magnetic resonance imaging and spectroscopy. A second cohort of (non-fasting) sera were obtained from HCV Research UK for comparative analyses: 150 treatment naïve patients and 100 non-viraemic patients post-SVR. HCV-G3 patients had significantly decreased serum apoB, non-HDL cholesterol concentrations, and more hepatic steatosis than those with HCV-G1. HCV-G3 patients also had significantly decreased serum levels of lathosterol, without significant reductions in desmosterol. Lipidomic analysis showed lipid species associated with reverse cholesterol transport pathway in HCV-G3. We demonstrated that compared to HCV-G1, HCV-G3 infection is characterised by low LDL cholesterol levels, with preferential suppression of cholesterol synthesis via lathosterol, associated with increasing hepatic steatosis. The genotype-specific lipid disturbances may shed light on genotypic variations in liver disease progression and promotion of hepatocellular cancer in HCV-G3.