bluuebunny/crossref_metadata_2025 huggingface dataset:
Extending the Field of Extended Language: A Literature Review on Figurative Language Processing in Neurodevelopmental Disorders
Authors: Chahboun S. , Kvello Ø. , Page A. G.
Published: July 2021

Figurative and extended uses of language are nonliteral utterances such as irony, sarcasm, and idioms and comprise a core part of social interaction. Children with typical development (TD) show a progressive adultlike understanding of figurative language around the age of ten. In contrast, individuals with neurodevelopmental disorders such as autism spectrum disorder (ASD), attention deficit and hyperactivity disorder (ADHD), or developmental language disorder often display difficulties with figurative language. However, these difficulties are a puzzle in that the actual underlying causes remain unclear. Those individuals who struggle with understanding figurative language need support through effective interventions. These should be based on solid research findings, which is often problematic as research in this field is characterized by conflicting and incomplete findings. The intention of this study is to conduct a literature review of both available studies and those intervention programs that seek to improve figurative language abilities in these atypical populations. This review will not only provide an overview of available intervention programs but also reveal the research gaps through critically appraising earlier studies. This is done as, in a manner of speaking, research reflects our theoretical understanding of the topic at hand, while interventions reflect the ways in which they are manifested into practice. This will serve to give the reader a more complete overview of the state of knowledge on figurative language and neurodevelopmental disorders. This article may be read for an overview of the field, but it also aims to point out the areas where additional research is needed. For instance, while figurative language takes many forms, there is a disproportionate scholarly focus on metaphors compared to other types. We will ultimately highlight promising approaches and make suggestions for future directions in terms of research and practice.
In-hospital Heart Rate Reduction With Beta Blockers and Ivabradine Early After Recovery in Patients With Acute Decompensated Heart Failure Reduces Short-Term Mortality and Rehospitalization
Authors: Faragli Alessandro , Tano Giuseppe Di , Carlini Caterina De , Nassiacos Daniel , Gori Mauro , Confortola Giada , Lo Muzio Francesco Paolo , Rapis Konstantinos , Abawi Dawud , Post Heiner , Kelle Sebastian , Pieske Burkert , Alogna Alessio , Campana Carlo
Published: July 2021

Objective: In the past years, heart rate (HR) has emerged as a highly relevant modifiable risk factor for heart failure (HF) patients. However, most of the clinical trials so far evaluated the role of HR in stable chronic HF cohorts. The aim of this multi-center, prospective observational study was to assess the association between HR and therapy with HR modulators (beta blockers, ivabradine, or a combination of ivabradine and beta blockers) at hospital discharge with patients' cardiovascular mortality and re-hospitalization at 6 months in acutely decompensated HF patients.

Materials and Methods: We recruited 289 HF patients discharged alive after admission for HF decompensation from 10 centers in northern Italy over 9 months (from April 2017 to January 2018). The primary endpoint was the combination of cardiovascular mortality or re-hospitalizations for HF at 6 months.

Results: At 6 months after discharge, 64 patients were readmitted (32%), and 39 patients died (16%). Multivariate analysis showed that HR at discharge ≥ 90 bpm (OR = 8.47; p = 0.016) independently predicted cardiovascular mortality, while therapy with beta blockers at discharge was found to reduce the risk of the composite endpoint. In patients receiving HR modulators the event rates for the composite endpoint, all-cause mortality, and cardiovascular mortality were lower than in patients not receiving HR modulators.

Conclusions: Heart rate at discharge ≥90 bpm predicts cardiovascular mortality, while therapy with beta blockers is negatively associated with the composite endpoint of cardiovascular mortality and hospitalization at 6 months in acutely decompensated HF patients. Patients receiving a HR modulation therapy at hospital discharge showed the lowest rate of cardiovascular mortality and re-hospitalization.
Feasibility Study for the Fast Periodic Pulsed Reactor with UO2 Fuel
Authors: Zhang Liang , Jiang Xinbiao , Zhang Xinyi , Ma Tengyue , Chen Sen , Wang Lipeng , Li Da , Chen Lixin
Published: July 2021

In order to study the feasibility of the fast periodic pulsed reactor with UO2 as fuel (abbreviated as FPPRU), the core models with different load schemes are designed. Neutronic characteristics of two typical design schemes are compared, and the better design scheme is determined. The critical search method is established for analyzing the reactor dynamics. Furthermore, the theoretical estimation formulas are derived to study the factors affecting the reactor dynamics clearly and intuitively. The reactor dynamics of the fast periodic pulsed reactor with UO2 and PuO2 as fuel are compared. The thermal hydraulic characteristic of FPPRU is studied with the sub-channel model. The results show that the design scheme of the FPPRU meets the demand of neutronics and thermal hydraulics safety. Meanwhile, the pulse parameter quality of the FPPRU with UO2 as fuel is not as good as that of IBR-2 with PuO2 as fuel.
A Critical Survey on Renewable Energy Applications in the Philippines and China: Present Challenges and Perspectives
Authors: Li Xin , Wang Haizhi , Lu Yuanru , Li Wanlin
Published: July 2021

China’s Belt and Road (B&R) initiative provides new ideas and opportunities for international cooperation. Renewable energy plays a crucial role not only in the national sustainable development framework of China and the Philippines but also in bilateral cooperation between them. However, some obstacles still need to be addressed because renewable energy cooperation between China and the Philippines has not been thoroughly and comprehensively studied to date. Based on an in-depth analysis of current renewable energy cooperation between China and the Philippines, this paper employs PESTEL analysis to fully investigate the cooperative advantages and disadvantages by considering politics (P), economy (E), society (S), technology (T), environment (E), and legislation (L) and proposes several constructive suggestions. The ultimate purpose was to design feasible schemes to ensure the sufficient utilization of renewable energy and the construction of integrated power grid systems to meet shortages of electricity supply especially in the isolated small islands in the Philippines through cooperation with China. In particular, it offers valuable advice concerning the U.S.-China trade war and COVID- 19 pandemic, outlining how cooperation in the exploitation of potential renewable energy is vital.
Impact of Short-Term Emission Control Measures on Air Quality in Nanjing During the Jiangsu Development Summit
Authors: Zhang Haoran , Tang Keqin , Feng Weihang , Yan Xintian , Liao Hong , Li Nan
Published: July 2021

This study analyzed the effectiveness of temporary emission control measures on air quality of Nanjing, China during the Jiangsu Development Summit (JDS). We employed a regional chemistry model WRF-Chem to simulate air pollutants in Nanjing and compared the results to surface observations and satellite retrievals. During the JDS, air pollutant emissions from industry and transportation sectors largely decreased by 50–67% due to the short-term emission control measures such as reducing coal combustions, shutting down factories, and partially limiting traffic. Benefiting from the emission control, the simulated concentrations of PM2.5, NO2, SO2, CO and VOCs in Nanjing decreased by 17%, 20%, 20%, 19%, and 15% respectively, consistent with the surface and satellite observations. However, both the observed and simulated O3 increased by 3–48% during the JDS, which was mainly due to the remarkable NOx emission reduction (26%) in the downtown of Nanjing where the O3 production regime was mainly VOC-controlled. In addition, the atmospheric oxidation capacity and further the sulfur oxidation ratio, were facilitated by the elevated O3, which led to variable mitigation efficiencies of different secondary PM2.5 compositions. Our study offers an opportunity for understanding the coordinated control of PM2.5 and O3 in typical city clusters, and can provide implications for future mitigation actions.
Community Bioacoustics: Studying Acoustic Community Structure for Ecological and Conservation Insights
Authors: Chhaya Vaibhav , Lahiri Sutirtha , Jagan M. Abhinava , Mohan Ram , Pathaw Nafisa A. , Krishnan Anand
Published: July 2021

The diversity of animal acoustic signals has evolved due to multiple ecological processes, both biotic and abiotic. At the level of communities of signaling animals, these processes may lead to diverse outcomes, including partitioning of acoustic signals along multiple axes (divergent signal parameters, signaling locations, and timing). Acoustic data provides information on the organization, diversity and dynamics of an acoustic community, and thus enables study of ecological change and turnover in a non-intrusive way. In this review, we lay out how community bioacoustics (the study of acoustic community structure and dynamics), has value in ecological monitoring and conservation of diverse landscapes and taxa. First, we review the concepts of signal space, signal partitioning and their effects on the structure of acoustic communities. Next, we highlight how spatiotemporal ecological change is reflected in acoustic community structure, and the potential this presents in monitoring and conservation. As passive acoustic monitoring gains popularity worldwide, we propose that the analytical framework of community bioacoustics has promise in studying the response of entire suites of species (from insects to large whales) to rapid anthropogenic change.
How Do Non-driving-related Tasks Affect Engagement Under Highly Automated Driving Situations? A Literature Review
Authors: Jaussein Marie , Lévêque Lucie , Deniel Jonathan , Bellet Thierry , Tattegrain Hélène , Marin-Lamellet Claude
Published: July 2021

Driving automation has become a trending topic over the past decade, as recent technical and technological improvements have created hope for a possible short-term release of partially automated vehicles. Several research teams have been exploring driver performance during control transitions performed under highly automated driving (i.e., while resuming manual driving, when facing a critical situation for instance). In this paper, we present a state of the art of studies dealing with control transitions as well as the concept of non-driving-related task (NDRT) engagement. More specifically, we aim to provide a global view on how task engagement is investigated in the literature. Two main utilisations of task engagement emerged from our literature review: its manipulation as independent variable to vary the driver’s engagement state before a control transition, and its measurement as dependent variable to compare its variation to driving behaviour variables during a control transition. Furthermore, we propose a new perspective on control transition, which was so far studied through a techno-centric approach; research works were indeed designed in function of the system state. Our article suggests a more cognitive-centred view by taking in account the evolution of engagement mechanisms along control transition stages. Finally, we provide a categorisation of engagement mechanisms’ variables involved during these different stages, with a view to facilitate future investigations on the driver’s engagement state during this crucial phase of highly automated driving.
Case Report: Novel NIPBL Variants Cause Cornelia de Lange Syndrome in Chinese Patients
Authors: Peng Ying , Liang Changbiao , Xi Hui , Yang Shuting , Hu Jiancheng , Pang Jialun , Liu Jing , Luo Yingchun , Tang Chengyuan , Xie Wanqin , Wang Hua
Published: July 2021

Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. Mutation in the NIPBL gene accounts for nearly 60% of the cases. This study reports the clinical and genetic findings of three cases of CdLS from unrelated Chinese families. Clinically, all the three cases were classified as classic CdLS based on the cardinal (distinctive facial features and limb malformations) and suggestive (developmental delay, growth retardation, microcephaly, hirsutism, etc.) manifestations. SNP array detected a novel de novo heterozygous microdeletion of 0.2 Mb [arr[GRCh37]5p13.2(36848530_37052821) × 1] that spans the first 43 exons of NIPBL in the fetus with nuchal translucency thickening in case 1. Whole-exome sequencing in family trios plus Sanger sequencing validation identified a de novo heterozygous NIPBL c.5566G>A (p.R1856G) mutation in the fetus with intrauterine growth retardation in case 2 and a novel de novo heterozygous NIPBL c.448dupA (p.S150Kfs*23) mutation in the proband (an 8-month-old girl) in case 3. The cases presented in this study may serve as references for increasing our understanding of the mutation spectrum of NIPBL in association with CdLS.
Characterizing the Role of Glycogen Synthase Kinase-3α/β in Macrophage Polarization and the Regulation of Pro-Atherogenic Pathways in Cultured Ldlr-/- Macrophages
Authors: Patel Sarvatit , Werstuck Geoff
Published: July 2021

The molecular and cellular mechanisms that link cardiovascular risk factors to the initiation and progression of atherosclerosis are not understood. Recent findings from our laboratory indicate that endoplasmic reticulum (ER) stress signaling through glycogen synthase kinase (GSK)-3α/β induces pro-atherosclerotic pathways. The objective of this study was to define the specific roles of GSK3α and GSK3β in the activation of pro-atherogenic processes in macrophages. Bone marrow derived macrophages (BMDM) were isolated from low-density lipoprotein receptor knockout (Ldlr-/-) mice and Ldlr-/- mice with myeloid deficiency of GSK3α and/or GSK3β. M1 and M2 macrophages were used to examine functions relevant to the development of atherosclerosis, including polarization, inflammatory response, cell viability, lipid accumulation, migration, and metabolism. GSK3α deficiency impairs M1 macrophage polarization, and reduces the inflammatory response and lipid accumulation, but increases macrophage mobility/migration. GSK3β deficiency promotes M1 macrophage polarization, which further increases the inflammatory response and lipid accumulation, but decreases macrophage migration. Macrophages deficient in both GSK3α and GSK3β exhibit increased cell viability, proliferation, and metabolism. These studies begin to delineate the specific roles of GSK3α and GSK3β in macrophage polarization and function. These data suggest that myeloid cell GSK3α signaling regulates M1 macrophage polarization and pro-atherogenic functions to promote atherosclerosis development.
Two Amphioxus ApeC-Containing Proteins Bind to Microbes and Inhibit the TRAF6 Pathway
Authors: Li Jin , Li Yuhui , Fan Zhaoyu , Chen Shenghui , Yan Xinyu , Yue Zirui , Huang Guangrui , Liu Shumin , Zhang Hao , Chen Shangwu , Dong Meiling , Xu Anlong , Huang Shengfeng
Published: July 2021

The apextrin C-terminal (ApeC) domain is a class of newly discovered protein domains with an origin dating back to prokaryotes. ApeC-containing proteins (ACPs) have been found in various marine and aquatic invertebrates, but their functions and the underlying mechanisms are largely unknown. Early studies suggested that amphioxus ACP1 and ACP2 bind to bacterial cell walls and have a role in immunity. Here we identified another two amphioxus ACPs (ACP3 and ACP5), which belong to the same phylogenetic clade with ACP1/2, but show distinct expression patterns and sequence divergence (40-50% sequence identities). Both ACP3 and ACP5 were mainly expressed in the intestine and hepatic cecum, and could be up-regulated after bacterial challenge. Both prokaryotic-expressed recombinant ACP3 and ACP5 could bind with several species of bacteria and yeasts, showing agglutinating activity but no microbicidal activity. ELISA assays suggested that their ApeC domains could interact with peptidoglycan (PGN), but not with lipoteichoic acid (LTA), lipopolysaccharides (LPS) and zymosan A. Furthermore, they can only bind to Lys-type PGN from Staphylococcus aureus, but not to DAP-type PGN from Bacillus subtilis and not to moieties of PGN such as MDPs, NAMs and NAGs. This recognition spectrum is different from that of ACP1/2. We also found that when expressed in mammalian cells, ACP3 could interact with TRAF6 via a conserved non-ApeC region, which inhibited the ubiquitination of TRAF6 and hence suppressed downstream NF-κB activation. This work helped define a novel subfamily of ACPs, which have conserved structures, and have related yet diversified molecular functions. Its members have dual roles, with ApeC as a lectin and a conserved unknown region as a signal transduction regulator. These findings expand our understanding of the ACP functions and may guide future research on the role of ACPs in different animal clades.
Novel Application of 210Po-210Pb Disequilibria to Date Snow, Melt Pond, Ice Core, and Ice-Rafted Sediments in the Arctic Ocean
Authors: Baskaran Mark , Krupp Katherine
Published: July 2021

We collected surface ocean water, snow, grab ice, ice core, melt pond and ice-rafted sediment (IRS) from 5 ice stations during the Western Arctic US GEOTRACES cruise (USGCG Healy; August 10 – October 7, 2015) and analyzed for210Po (T1/2= 138.4 days) and210Pb (T1/2= 22.3 years) in dissolved and particulate phases (snow, grab ice, ice core, surface seawater) to investigate the210Po:210Pb disequilibria in these matrices. Thirteen aerosol samples, using a large-volume aerosol sampler (PM10), from Dutch Harbor, AK to North Pole, were also collected and analyzed for210Po/210Pb to quantify the atmospheric depositional input to the snow and surface waters. Falling snowfall is tagged with210Po/210Pb ratio (AR) similar to that in the air column from the cloud condensation height to air-sea interface. From the measured AR in aerosol and snow, modeling the sources of210Po and210Pb input to the melt pond, and measured disequilibrium in ice core and ice-rafted sediment, we show210Po/210Pb AR is a novel chronometer to date snow, ice core, melt pond, and IRS. The calculated mean ages of aerosol, snow, melt pond and IRS are 12 ± 7 (n= 13), 13 ± 11 (n= 6), 60 ± 14 (n= 4), and 87 ± 23 (n= 6) days, respectively. The average IRS age corresponds to an average drift velocity of sediment-laden ice of 0.18 ± 0.06 (n= 6) m s–1. We report highly elevated levels of210Po and210Pb in snow and melt pond compared to those in Arctic surface seawater and enrichment of210Po compared to210Pb onto particles extracted from snow, ice and melt ponds. The observed disequilibrium between210Po and210Pb in ice could serve as a quantitative tool in delineating multiple-year ice from seasonal ice as well as a metric in quantifying the speed of ice/snow melting and delay in autumn freeze.
Governing the Land-Sea Interface to Achieve Sustainable Coastal Development
Authors: Singh Gerald G. , Cottrell Richard S. , Eddy Tyler D. , Cisneros-Montemayor Andrés Miguel
Published: July 2021

Coastal regions are essential to achieving the Sustainable Development Goals (SDGs) given their importance for human habitation, resource provisioning, employment, and cultural practice. They are also regions where different ecological, disciplinary, and jurisdictional boundaries both overlap and are obscured. We thus propose the land-sea interface as areas where governance systems are most in need of frameworks for systems analysis to meet the SDGs—which are inherently interconnected— and integrate complex interdependencies between human livelihoods, energy, transport, food production, and nutrient flows (among others). We propose a strategic land-sea governance framework built on the sustainable transitions literature to plan for governance to achieve sustainable development across the land-sea interface. To illustrate our proposal, we compare governance planning processes across four case-based scenarios: an industrialized coastal country, a least developed coastal country, a developing coastal country with local dependencies on ocean resources, and a small island developing state primarily dependent on tourism. Through the lens of aligning governance actors and actions vertically (subnational to national), horizontally (across sectors), and programmatically (from goals to implementation), we propose scales at which governance systems may be misaligned, such as where different agencies that affect marine systems have conflicting visions and goals, leading to stalled progress or counterproductive actions. Where possible, we also highlight strategies to align across scales of high level strategic policy, tactical scale institutional mandates and cooperation, and on the ground activities and operations, such as aligning actors based on an analysis of interdependencies of goals.
Characterizing the Non-linear Interactions Between Tide, Storm Surge, and River Flow in the Delaware Bay Estuary, United States
Authors: Xiao Ziyu , Yang Zhaoqing , Wang Taiping , Sun Ning , Wigmosta Mark , Judi David
Published: July 2021

Low-lying coastal areas in the mid-Atlantic region are prone to compound flooding resulting from the co-occurrence of river floods and coastal storm surges. To better understand the contribution of non-linear tide-surge-river interactions to compound flooding, the unstructured-grid Finite Volume Community Ocean Model was applied to simulate coastal storm surge and flooding in the Delaware Bay Estuary in the United States. The model was validated with tide gauge data in the estuary for selected hurricane events. Non-linear interactions between tide-surge-river were investigated using a non-stationary tidal analysis method, which decomposes the interactions’ components at the frequency domain. Model results indicated that tide-river interactions damped semidiurnal tides, while the tide-surge interactions mainly influenced diurnal tides. Tide-river interactions suppressed the water level upstream while tide-surge interaction increased the water level downstream, which resulted in a transition zone of damping and enhancing effects where the tide-surge-river interaction was prominent. Evident compound flooding was observed as a result of non-linear tide-surge-river interactions. Furthermore, sensitivity analysis was carried out to evaluate the effect of river flooding on the non-linear interactions. The transition zone of damping and enhancing effects shifted downstream as the river flow rate increased.
A Distinct Difference Between Air and Mucosal Temperatures in Human Respiratory Tract
Authors: Khosravi Mehdi , Lin Ruei-Lung , Maskey Ashish P. , Pandey Subodh , Lin An-Hsuan , Lee Lu-Yuan
Published: July 2021

Extensive evidence indicates that several types of temperature-sensitive ion channels are abundantly expressed in the sensory nerves innervating airway mucosa. Indeed, airway temperature is known to play an important role in regulating respiratory functions. However, the actual airway mucosal temperature and its dynamic changes during the respiratory cycle have not been directly measured. In previous studies, airway tissue temperature was often estimated by indirect measurement of the peak exhaled breath temperature (PEBT). In view of the poor thermal conductivity of air, we believe that the airway tissue temperature cannot be accurately determined by the exhaled air temperature, and this study aimed to test this hypothesis. We applied a miniature rapid-response temperature probe to measure directly the mucosal temperatures of trachea, major, lobar, and segmental bronchi in eight human subjects during a bronchoscopy procedure. Unlike the air temperature in the airway lumen, the mucosal temperature in these airway segments remained relatively stable and did not exhibit the phasic changes synchronous with respiratory cycles. The airway mucosal temperature increased progressively from the extra-thoracic trachea (35.7 ± 0.2°C) toward the segmental bronchus (36.9 ± 0.2°C). Most importantly, the temperatures measured directly at the mucosa of all these airway segments were substantially higher than the PEBT (31.7 ± 0.8°C). The recent findings of a close association between an increased PEBT and airway tissue inflammation have revealed the implication and potential of incorporating the PEBT measurement in the future clinical diagnosis of airway inflammation. Therefore, it is imperative to recognize this distinct difference in temperature between airway mucosa and exhaled air.
Rhamnolipid Enhances the Nitrogen Fixation Activity of Azotobacter chroococcum by Influencing Lysine Succinylation
Authors: Li Jin , Pan Hu , Yang Hui , Wang Chong , Liu Huhu , Zhou Hui , Li Peiwang , Li Changzhu , Lu Xiangyang , Tian Yun
Published: July 2021

The enhancement of nitrogen fixation activity of diazotrophs is essential for safe crop production. Lysine succinylation (KSuc) is widely present in eukaryotes and prokaryotes and regulates various biological process. However, knowledge of the extent of KSuc in nitrogen fixation of Azotobacter chroococcum is scarce. In this study, we found that 250 mg/l of rhamnolipid (RL) significantly increased the nitrogen fixation activity of A. chroococcum by 39%, as compared with the control. Real-time quantitative reverse transcription PCR (qRT-PCR) confirmed that RL could remarkably increase the transcript levels of nifA and nifHDK genes. In addition, a global KSuc of A. chroococcum was profiled using a 4D label-free quantitative proteomic approach. In total, 5,008 KSuc sites were identified on 1,376 succinylated proteins. Bioinformatics analysis showed that the addition of RL influence on the KSuc level, and the succinylated proteins were involved in various metabolic processes, particularly enriched in oxidative phosphorylation, tricarboxylic acid cycle (TCA) cycle, and nitrogen metabolism. Meanwhile, multiple succinylation sites on MoFe protein (NifDK) may influence nitrogenase activity. These results would provide an experimental basis for the regulation of biological nitrogen fixation with KSuc and shed new light on the mechanistic study of nitrogen fixation.
Effect of Sublethal Prenatal Endotoxaemia on Murine Placental Transport Systems and Lipid Homeostasis
Authors: Reginatto Mila W. , Fontes Klaus Novaes , Monteiro Victoria R. S. , Silva Natalia L. , Andrade Cherley Borba Vieira , Gomes Hanailly Ribeiro , Imperio Guinever E. , Bloise Flavia Fonseca , Kluck George Eduardo Gabriel , Atella Georgia Correa , Matthews Stephen G. , Bloise Enrrico , Ortiga-Carvalho Tania M.
Published: July 2021

Infection alters the expression of transporters that mediate the placental exchange of xenobiotics, lipids and cytokines. We hypothesized that lipopolysaccharide (LPS) modifies the expression of placental transport systems and lipid homeostasis. LPS (150 μg/kg; i.p.) treatments were administered for 4 h or 24 h, animals were euthanized at gestational days (GD) 15.5 or 18.5, and maternal blood, fetuses and placentae were collected. Increased rates of fetal demise were observed at GD15.5 following LPS treatment, whereas at GD18.5, high rates of early labour occurred and were associated with distinct proinflammatory responses. Lipopolysaccharide did not alter ATP-binding cassette (ABC) transporter mRNA expression but decreased fatty acid binding protein associated with plasma membrane (Fabppm) at GD15.5 (LPS-4 h) and increased fatty acid translocase (Fat/Cd36) mRNA at GD18.5 (LPS-4 h). At the protein level, breast cancer-related protein (Bcrp) and ABC sub-family G member 1 (Abcg1) levels were decreased in the placental labyrinth zone (Lz) at GD15.5, whereas P-glycoprotein (P-gp) and Bcrp Lz-immunostaining was decreased at GD18.5. In the placental junctional zone (Jz), P-gp, Bcrp and Abcg1 levels were higher at GD18.5. Specific maternal plasma and placental changes in triacylglycerol, free fatty acid, cholesterol, cholesterol ester and monoacylglycerol levels were detected in a gestational age-dependent manner. In conclusion, LPS-increased risk of fetal death and early labour were associated with altered placental ABC and lipid transporter expression and deranged maternal plasma and placental lipid homeostasis. These changes may potentially modify fetal xenobiotic exposure and placental lipid exchange in cases of bacterial infection.
Dissecting Metabolism of Leaf Nodules in Ardisia crenata and Psychotria punctata
Authors: Schindler Florian , Fragner Lena , Herpell Johannes B. , Berger Andreas , Brenner Martin , Tischler Sonja , Bellaire Anke , Schönenberger Jürg , Li Weimin , Sun Xiaoliang , Schinnerl Johann , Brecker Lothar , Weckwerth Wolfram
Published: July 2021

Root-microbe interaction and its specialized root nodule structures and functions are well studied. In contrast, leaf nodules harboring microbial endophytes in special glandular leaf structures have only recently gained increased interest as plant-microbe phyllosphere interactions. Here, we applied a comprehensive metabolomics platform in combination with natural product isolation and characterization to dissect leaf and leaf nodule metabolism and functions in Ardisia crenata (Primulaceae) and Psychotria punctata (Rubiaceae). The results indicate that abiotic stress resilience plays an important part within the leaf nodule symbiosis of both species. Both species showed metabolic signatures of enhanced nitrogen assimilation/dissimilation pattern and increased polyamine levels in nodules compared to leaf lamina tissue potentially involved in senescence processes and photosynthesis. Multiple links to cytokinin and REDOX-active pathways were found. Our results further demonstrate that secondary metabolite production by endophytes is a key feature of this symbiotic system. Multiple anhydromuropeptides (AhMP) and their derivatives were identified as highly characteristic biomarkers for nodulation within both species. A novel epicatechin derivative was structurally elucidated with NMR and shown to be enriched within the leaf nodules of A. crenata. This enrichment within nodulated tissues was also observed for catechin and other flavonoids indicating that flavonoid metabolism may play an important role for leaf nodule symbiosis of A. crenata. In contrast, pavettamine was only detected in P. punctata and showed no nodule specific enrichment but a developmental effect. Further natural products were detected, including three putative unknown depsipeptide structures in A. crenata leaf nodules. The analysis presents a first metabolomics reference data set for the intimate interaction of microbes and plants in leaf nodules, reveals novel metabolic processes of plant-microbe interaction as well as the potential of natural product discovery in these systems.
Molecular and Cellular Studies Reveal Folding Defects of Human Ornithine Aminotransferase Variants Associated With Gyrate Atrophy of the Choroid and Retina
Authors: Montioli Riccardo , Sgaravizzi Giada , Desbats Maria Andrea , Grottelli Silvia , Voltattorni Carla Borri , Salviati Leonardo , Cellini Barbara
Published: July 2021

The deficit of human ornithine aminotransferase (hOAT) is responsible for gyrate atrophy (GA), a rare recessive inherited disorder. Although more than 60 disease-associated mutations have been identified to date, the molecular mechanisms explaining how each mutation leads to the deficit of OAT are mostly unknown. To fill this gap, we considered six representative missense mutations present in homozygous patients concerning residues spread over the hOAT structure. E. coli expression, spectroscopic, kinetic and bioinformatic analyses, reveal that the R154L and G237D mutations induce a catalytic more than a folding defect, the Q90E and R271K mutations mainly impact folding efficiency, while the E318K and C394Y mutations give rise to both folding and catalytic defects. In a human cellular model of disease folding-defective variants, although at a different extent, display reduced protein levels and/or specific activity, due to increased aggregation and/or degradation propensity. The supplementation with Vitamin B6, to mimic a treatment strategy available for GA patients, does not significantly improve the expression/activity of folding-defective variants, in contrast with the clinical responsiveness of patients bearing the E318K mutation. Thus, we speculate that the action of vitamin B6 could be also independent of hOAT. Overall, these data represent a further effort toward a comprehensive analysis of GA pathogenesis at molecular and cellular level, with important relapses for the improvement of genotype/phenotype correlations and the development of novel treatments.
RNA Polymerase III Subunit Mutations in Genetic Diseases
Authors: Lata Elisabeth , Choquet Karine , Sagliocco Francis , Brais Bernard , Bernard Geneviève , Teichmann Martin
Published: July 2021

RNA polymerase (Pol) III transcribes small untranslated RNAs such as 5S ribosomal RNA, transfer RNAs, and U6 small nuclear RNA. Because of the functions of these RNAs, Pol III transcription is best known for its essential contribution to RNA maturation and translation. Surprisingly, it was discovered in the last decade that various inherited mutations in genes encoding nine distinct subunits of Pol III cause tissue-specific diseases rather than a general failure of all vital functions. Mutations in the POLR3A, POLR3C, POLR3E and POLR3F subunits are associated with susceptibility to varicella zoster virus-induced encephalitis and pneumonitis. In addition, an ever-increasing number of distinct mutations in the POLR3A, POLR3B, POLR1C and POLR3K subunits cause a spectrum of neurodegenerative diseases, which includes most notably hypomyelinating leukodystrophy. Furthermore, other rare diseases are also associated with mutations in genes encoding subunits of Pol III (POLR3H, POLR3GL) and the BRF1 component of the TFIIIB transcription initiation factor. Although the causal relationship between these mutations and disease development is widely accepted, the exact molecular mechanisms underlying disease pathogenesis remain enigmatic. Here, we review the current knowledge on the functional impact of specific mutations, possible Pol III-related disease-causing mechanisms, and animal models that may help to better understand the links between Pol III mutations and disease.
α-Synuclein Regulates Peripheral Insulin Secretion and Glucose Transport
Authors: Wijesekara Nadeeja , Ahrens Rosemary , Wu Ling , Langman Tammy , Tandon Anurag , Fraser Paul E.
Published: July 2021

Aim

Population based studies indicate a positive association between type 2 diabetes (T2D) and Parkinson’s disease (PD) where there is an increased risk of developing PD in patients with T2D. PD is characterized by the abnormal accumulation of intraneuronal aggregated α-synuclein (α-syn) in Lewy bodies, which negatively impact neuronal viability. α-syn is also expressed in both pancreatic islets and skeletal muscle, key players in glucose regulation. Therefore, we examined the functional role of α-syn in these tissues.

Methods

Using mice lacking, overexpressing or transiently injected with α-syn, effects on glucose and insulin tolerance and insulin secretion were determined, with further characterization of the effects on GLUT4 translocation using GLUT4myc myotubes.

Results

Mice genetically ablated for α-syn became glucose intolerant and insulin resistant with hyperinsulinemia and reduced glucose-stimulated insulin secretion (GSIS). Mice overexpressing human α-syn are more insulin senstive and glucose tolerant compared to controls with increased GSIS. Injection of purified α-syn monomers also led to improved glucose tolerance and insulin sensitivity with hightened GSIS. α-syn monomer treatments increased surface GLUT4 levels in myotubes but without any significant change in Akt phosphorylation. The increase in cell surface GLUT4 was largely due to a large reduction in GLUT4 endocytosis, however, with a compensatory reduction in GLUT4 exocytosis.

Conclusion

Cumulatively, this data suggests that α-syn modulates both pancreatic beta cell function and glucose transport in peripheral tissues, thereby playing a pivitol role in the maintenance of normal glucose homeostasis.
Hormonal Contraception and Violent Death: The Physiological and Psychological Links
Authors: Lanfranchi Angela
Published: July 2021

In the past decade, two large prospective cohort studies of British and American women have been conducted which found a statistically significant increase in the risk of violent death in ever-users of hormonal contraceptives. Research on the effects of hormonal contraceptives upon the behaviors of intimate partners and on the physiology of women using hormonal contraceptives has provided insight into the possible basis for the resulting increase in violent death. This review examines the changes that are potential contributors to the reported increase.
The Immunopathogenesis of Neuroinvasive Lesions of SARS-CoV-2 Infection in COVID-19 Patients
Authors: Alipoor Shamila D. , Mortaz Esmaeil , Varahram Mohammad , Garssen Johan , Adcock Ian M.
Published: July 2021

The new coronavirus disease COVID-19 was identified in December 2019. It subsequently spread across the world with over 125 M reported cases and 2.75 M deaths in 190 countries. COVID-19 causes severe respiratory distress; however, recent studies have reported neurological consequences of infection by the COVID-19 virus SARS-CoV-2 even in subjects with mild infection and no initial neurological effects. It is likely that the virus uses the olfactory nerve to reach the CNS and that this transport mechanism enables virus access to areas of the brain stem that regulates respiratory rhythm and may even trigger cell death by alteration of these neuronal nuclei. In addition, the long-term neuronal effects of COVID-19 suggest a role for SARS-CoV-2 in the development or progression of neurodegerative disease as a result of inflammation and/or hypercoagulation. In this review recent findings on the mechanism(s) by which SARS-CoV-2 accesses the CNS and induces neurological dysregulation are summarized.
Disruptions of Sustained Spatial Attention Can Be Resistant to the Distractor’s Prior Reward Associations
Authors: Bachman Matthew D. , Hunter Madison N. , Huettel Scott A. , Woldorff Marty G.
Published: July 2021

Attention can be involuntarily biased toward reward-associated distractors (value-driven attentional capture, VDAC). Yet past work has primarily demonstrated this distraction phenomenon during a particular set of circumstances: transient attentional orienting to potentially relevant stimuli occurring in our visual environment. Consequently, it is not well-understood if reward-based attentional capture can occur under other circumstances, such as during sustained visuospatial attention. Using EEG, we investigated whether associating transient distractors with reward value would increase their distractibility and lead to greater decrements in concurrent sustained spatial attention directed elsewhere. Human participants learned to associate three differently colored, laterally presented squares with rewards of varying magnitude (zero, small, and large). These colored squares were then periodically reintroduced as distractors at the same lateral locations during a demanding sustained-attention rapid-serial-visual-presentation (RSVP) task at the midline. Behavioral and neural evidence indicated that participants had successfully learned and maintained the reward associations to the distractors. During the RSVP task, consistent with prior work, we found that the distractors generated dips in the instantaneous amplitude of the steady-state visual evoked potentials (SSVEPs) elicited by the midline RSVP stimuli, indicating that the distractors were indeed transiently disrupting sustained spatial attention. Contrary to our hypotheses, however, the magnitude of this dip did not differ by the magnitude of the distractor’s reward associations. These results indicate that while sustained spatial attention can be impaired by the introduction of distractors at another location, the main distraction process is resistant to the distractors’ reward associations, thus providing evidence of an important boundary condition to value-driven attentional capture.
Conductivity Tensor Imaging of the Human Brain Using Water Mapping Techniques
Authors: Marino Marco , Cordero-Grande Lucilio , Mantini Dante , Ferrazzi Giulio
Published: July 2021

Conductivity tensor imaging (CTI) has been recently proposed to map the conductivity tensor in 3D using magnetic resonance imaging (MRI) at the frequency range of the brain at rest, i.e., low-frequencies. Conventional CTI mapping methods process the trans-receiver phase of the MRI signal using the MR electric properties tomography (MR-EPT) technique, which in turn involves the application of the Laplace operator. This results in CTI maps with a low signal-to-noise ratio (SNR), artifacts at tissue boundaries and a limited spatial resolution. In order to improve on these aspects, a methodology independent from the MR-EPT method is proposed. This relies on the strong assumption for which electrical conductivity is univocally pre-determined by water concentration. In particular, CTI maps are calculated by combining high-frequency conductivity derived from water maps and multi b-value diffusion tensor imaging (DTI) data. Following the implementation of a pipeline to optimize the pre-processing of diffusion data and the fitting routine of a multi-compartment diffusivity model, reconstructed conductivity images were evaluated in terms of the achieved spatial resolution in five healthy subjects scanned at rest. We found that the pre-processing of diffusion data and the optimization of the fitting procedure improve the quality of conductivity maps. We achieve reproducible measurements across healthy participants and, in particular, we report conductivity values across subjects of 0.55 ± 0.01Sm, 0.3 ± 0.01Sm and 2.15 ± 0.02Sm for gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF), respectively. By attaining an actual spatial resolution of the conductivity tensor close to 1 mm in-plane isotropic, partial volume effects are reduced leading to good discrimination of tissues with similar conductivity values, such as GM and WM. The application of the proposed framework may contribute to a better definition of the head tissue compartments in electroencephalograpy/magnetoencephalography (EEG/MEG) source imaging and be used as biomarker for assessing conductivity changes in pathological conditions, such as stroke and brain tumors.
Clean Label Trade-Offs: A Case Study of Plain Yogurt
Authors: Maruyama Sara , Lim Juyun , Streletskaya Nadia A.
Published: July 2021

Consumer demand for clean label has risen in recent years. However, clean label foods with simple and minimalistic ingredient lists are often expensive to produce and/or may possess less desirable sensory qualities. Accordingly, understanding consumer preferences regarding the clean label trend would be of great interest to the food industry. Here we investigate how ingredient lists and associated sensory quality descriptions may influence consumer preferences using a hypothetical choice experiment. In particular, we test the impacts of four common stabilizers (carrageenan, corn starch, milk protein concentrate, and pectin) and textural characteristics on preferences and willingness to pay for plain yogurt. A total of 250 yogurt consumers participated in the study. The results of a mixed logit analysis suggest that clean labeling significantly increases the likelihood of consumer choice, while poor texture reduces consumer choice. More importantly, the negative impact of poor texture seems to be less significant for clean label yogurts compared to that for yogurts with longer ingredient lists. Among all stabilizers, corn starch in particular has a significant negative impact on consumer choice. The estimated average consumer willingness to pay for clean labels is between $2.54 and $3.53 for 32 oz yogurt formulations. Furthermore, clean labels minimize the negative impact of textural defects with consumers willing to pay an estimated premium of $1.61 for the family size yogurt with a simple ingredient list. Results of latent class modeling reveal two classes of consumers with similar patterns of demand who prefer clean labels and, on average, would rather purchase a yogurt with a textural defect than opt out of purchasing a yogurt entirely. Implications for the food industry are discussed.
A Genome-Scale CRISPR Knock-Out Screen Identifies MicroRNA-5197-5p as a Promising Radiosensitive Biomarker in Colorectal Cancer
Authors: Yu Shijun , Li Li , Fan Kailing , Li Yandong , Gao Yong
Published: July 2021

Radioresistance is one of the main reasons causing unsatisfactory curative effects of ionizing radiation (IR) against colorectal cancer (CRC). However, its underlying mechanisms remain unclear yet. In the present study, we applied a genome-scale CRISPR knockout screen in combination of NGS sequencing upon CRC cell lines to explore regulatory factors involved radioresistance of CRC, and 3 candidate genes were identified. Cytotoxicity of IR was determined by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and apoptosis assay, and microRNA-5197-5p (miR-5197) was found to significantly enhance the cytotoxicity of IR to CRC cells. By further mechanistic investigation, we demonstrated that miR-5197 directly targeted CDK6 and inhibited its expression in RKO cells, which induced cell cycle arrest at G1/S phase and inhibited cell division, thereby radiosensitivity was enhanced by miR-5197. Our findings revealed that miR-5197 might be a critical factor regulating CRC cell radiosensitivity and provided novel insights into the development of therapeutic strategies for CRC patients who are resistant to IR.
Intensive Debulking Chemotherapy Improves the Short-Term and Long-Term Efficacy of Anti-CD19-CAR-T in Refractory/Relapsed DLBCL With High Tumor Bulk
Authors: Lyu Cuicui , Cui Rui , Wang Jia , Mou Nan , Jiang Yanyu , Li Wei , Deng Qi
Published: July 2021

Anti-CD19 chimeric antigen receptor T (CAR-T) therapy has achieved remarkable effects in refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL). However, when high tumor bulk occurs, patients tend to early progression after CAR-T therapy. Here, we investigated whether pretreatment with intensive debulking chemotherapy could improve the outcome of CAR-T in such patients. Fifty-seven patients with R/R DLBCL were enrolled, and 42 patients received anti-CD19-CAR-T therapy, among which, 25 patients (the combined group) with high tumor bulk received debulking chemotherapy and anti-CD19-CAR-T therapy sequentially. Another 17 patients (the control group) without high tumor bulk received anti-CD19-CAR-T therapy only. According to the response to debulking chemotherapy, patients of the combined group were divided into chemo-sensitive and chemo-refractory groups. Within 2 months, the objective response rate (ORR) was higher in the chemo-sensitive group than in the chemo-refractory group (P = 0.031). Grades 1–3 cytokine release syndrome (CRS) was reported, and no difference was shown in CRS grade distribution between the chemo-sensitive and chemo-refractory groups (P = 0.514). The chemo-sensitive group demonstrated longer overall survival (OS) than the chemo-refractory group (P = 0.042). Of the chemo-sensitive group, the 1-year disease free survival (DFS) and OS rates were 52.6 and 57.9%, respectively. Besides, no significant differences were found in ORR, DFS, and OS between the chemo-sensitive and control groups (ORR: P = 0.593; DFS: P = 0.762; OS: P = 0.531). In summary, effective debulking chemotherapy improved the short-term ORR and long-term OS of CAR-T therapy in R/R DLBCL with high tumor bulk, with outcomes comparable to those of R/R DLBCL without high tumor bulk. The clinical trial of our study was registered at http://www.chictr.org.cn/index.aspx as ChiCTR-ONN-16009862 and ChiCTR1800019622.

Clinical Trial Registration

http://www.chictr.org.cn/index.aspx, identifier (ChiCTR-ONN-16009862 and ChiCTR1800019622).