bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced spatially hybrid fluid‐kinetic modelling of plasma‐edge neutrals and application to ITER case using SOLPS‐ITER
Authors: Van Uytven W. , Dekeyser W. , Blommaert M. , Horsten N. , Marandet Y. , Baelmans M.
Published: February 2022

A spatially hybrid fluid‐kinetic approach for the efficient simulation of plasma‐edge neutrals is extended with a kinetic‐fluid condensation process and an automated approach to select a fluid or kinetic treatment at each point along the divertor targets. With the proposed hybrid fluid‐kinetic methods, the dominant charge–exchange reaction can be largely removed from the kinetic neutral simulation. The hybrid methods achieve quantitative agreement with the standard kinetic approach, with relative errors on the peak target plasma density and peak target ion flux density of 5–30%, while the Central Processing Unit (CPU) time for the kinetic neutral solver is reduced by a factor 3–6.
How early mathematics interventions support mathematics vocabulary learning: A content analysis
Authors: Nelson Gena , Carter Hannah
Published: February 2022

While there is a strong research base that supports intervening early in mathematics, research investigating the importance of mathematics vocabulary is still emerging. Practitioners and researchers may benefit from understanding how mathematics interventions support mathematics vocabulary acquisition, particularly for students who struggle with learning mathematics. Thus, the purpose of this study was to conduct a mathematics vocabulary content analysis across seven kindergarten and first‐grade mathematics interventions. Across the intervention lessons, we recorded suggested teacher and student actions related to mathematics vocabulary instruction. The results indicated the most common instructional strategies used to teach mathematics vocabulary include: providing students with the opportunity to apply the meaning of the vocabulary term (94.7%), using representations (66.4%), and asking students to respond to teacher prompts using the term (44.7%). Overall, 29.7% of lessons clearly defined vocabulary terms, and 5.8% of lesson objectives addressed teaching the definition of the term. We discuss implications for researchers and practitioners to supplement interventions with opportunities for students to learn, practise, and apply mathematics vocabulary.
Sharp‐based shoreface successions reconsidered in three‐dimensions: A forward stratigraphic modelling perspective
Authors: Willis Brian J. , Sun Tao , Ainsworth R. Bruce
Published: February 2022

Sea‐level fall is commonly inferred to generate a sharp‐based shoreface succession that displays an abrupt vertical transition from heterolithic, lower shoreface to sandy, upper shoreface deposits across a marine erosion surface. Three‐dimensional, process physics‐based, coupled hydrodynamic‐morphodynamic models are constructed to compare bedding architecture and facies patterns of wave‐dominated delta deposits preserved during normal (static sea level) and forced (falling sea level) regression and then transgression during subsequent sea‐level rise. The models suggest that wave‐dominated deltas will develop a sandy shoreface inner clinoform dipping from the subaerial delta plain to a relatively flat wave‐scoured subaqueous delta top, which is laterally separated from a delta front outer clinoform that dips from the subaqueous delta top edge to the shelf floor. As these systems prograde, deposits of these dual‐clinoforms will become vertically stacked and will be separated by a regressive surface of marine erosion. Significant grain‐size contrasts between these vertically stacked clinoform deposits reflect differences in sediment‐transport directions and sorting under river and wave‐driven littoral currents along the coast, and cannot be related uniquely to sea‐level changes. The marine erosion surface under a sharp‐based shoreface deposit records abrupt facies shift across a kilometres‐wide, wave‐eroded surface and defines a discontinuity in the preserved vertical succession. The continuity of a regressive surface of marine erosion mapped over many tens to hundreds of kilometres across mid‐shelf regions of some stratigraphic sequences reflects a gradual lateral shift in the position of littoral current erosion on a subaqueous delta top. Timelines cross such vertical lithic discontinuities throughout the extent of a prograding deposit, and the regressive surface of marine erosion thus has little chronostratigraphic significance. The results of these models suggest caution in inferring sea‐level changes from the character of vertical facies changes observed in individual well logs and isolated outcrop exposures.
Potential of chromatography and mass spectrometry for the differentiation of three series of positional isomers of 2‐(dimethoxyphenyl)‐N‐(2‐halogenobenzyl)ethanamines
Authors: Kupriyanova Olga V. , Shevyrin Vadim A. , Shafran Yuri M.
Published: February 2022

N‐(2‐substituted benzyl)‐2,5‐dimethoxyphenethylamines often cause severe poisonings which has led to their legal prohibition in many countries. At the same time, their positional isomers can be studied as potential therapeutic drugs. In this regard, the search for various approaches to differentiate these isomers is an important practical task, the solution of which would guarantee from identification errors during laboratory analysis. In this paper, the possibilities of differentiation of isomers varying in the position of two methoxy groups in the phenylethyl part of the molecule are considered on the example of compounds of NBF, NBCl, and NBBr series by chromatography‐mass spectrometry methods. Gas or liquid reverse‐phase chromatography in the proposed chromatographic separation modes has demonstrated their ability to resolve this problem reliably. Data on retention indices of isomeric compounds and their derivatives can serve as an additional identification criterion for gas chromatography–mass spectrometry (GC‐MS) analysis. Differentiation of NBF and NBCl isomers using electron ionization (EI) mass spectra is feasible only if both the spectrum of the compound and its N‐trifluoroacetyl derivative are registered; differentiation of NBBr positional isomers under these conditions does not require obtaining the derivatives. Using electrospray ion source, the compounds can easily be differentiated based on the distinctive features of their collision induced dissociation (CID) spectra recorded at low energy values, which also does not require the synthesis of derivatives. The data presented in current paper will be useful for analysis in laboratories providing the determination of narcotic drugs.
Structure‐guided stabilization of pathogen‐derived peptide‐HLA‐E complexes using non‐natural amino acids conserves native TCR recognition
Authors: Barber Claire , De Souza Victoria Arena , Paterson Rachel L. , Martin‐Urdiroz Magdalena , Mulakkal Nitha Charles , Srikannathasan Velupillai , Connolly Mary , Phillips Gwilym , Foong‐Leong Tein , Pengelly Robert , Karuppiah Vijaykumar , Grant Tressan , Dembek Marcin , Verma Anil , Gibbs‐Howe Dawn , Blicher Thomas H. , Knox Andrew , Robinson Ross A. , Cole David K. , Leonard Sarah
Published: February 2022

The nonpolymorphic class Ib molecule, HLA‐E, primarily presents peptides from HLA class Ia leader peptides, providing an inhibitory signal to NK cells via CD94/NKG2 interactions.

Although peptides of pathogenic origin can also be presented by HLA‐E to T cells, the molecular basis underpinning their role in antigen surveillance is largely unknown. Here, we solved a co‐complex crystal structure of a TCR with an HLA‐E presented peptide (pHLA‐E) from bacterial (Mycobacterium tuberculosis) origin, and the first TCR‐pHLA‐E complex with a noncanonically presented peptide from viral (HIV) origin. The structures provided a molecular foundation to develop a novel method to introduce cysteine traps using non‐natural amino acid chemistry that stabilized pHLA‐E complexes while maintaining native interface contacts between the TCRs and different pHLA‐E complexes. These pHLA‐E monomers could be used to isolate pHLA‐E‐specific T cells, with obvious utility for studying pHLA‐E restricted T cells, and for the identification of putative therapeutic TCRs.
Geomorphic response to historic and ongoing human impacts in a large lowland river
Authors: Mossa Joann , Chen Yin‐Hsuen
Published: February 2022

Lowland coastal plain rivers are important for navigation and ecosystems, having unique concerns regarding water and sediment management. The Apalachicola River in Florida, the lower end of the ACF (Apalachicola–Chattahoochee–Flint) system, had historical modifications beginning in the 1800s. Most impacts are attributable to the Apalachicola Navigation Project in the latter half of the 20th century, which included dredging, disposal, rock and snag removal, artificial cutoffs, and wing‐dike building.

As one of few studies using paired hydrographic surveys over a long reach and time (170 km, 50 years), we defined four zones of bed elevation change between 1960 and 2010 based on the cumulative thalweg elevation plots. The river has four bed change zones: (1) uppermost, marked degradation from river mile (RM) 106 to 85 because of dam construction; (2) middle, minimal degradation from RM 85 to 34; (3) artificial cutoff zone, highest degradation, from RM 34 to 27; and (4) lowermost zone, aggradation from RM 27 to Apalachicola Bay because of upstream bed and bank sediment disturbances. Artificial cutoffs and lithology influence lateral migration, with rates being highest in cutoff zones and least in areas with some bedrock upstream and finer sediments downstream. Length changes from 1941 to 2019 are stable, except for the middle reach, which lengthened nearly 10%, and the lower non‐tidal reach, where length shortened with cutoffs then regained in subsequent decades. Minimizing disturbance has led to 18% of the sand bar area revegetating since a decade of dredging ended. This framework helps in understanding historic and ongoing human activities, notably upstream water consumption, connectivity changes, sediment inputs, and climate change, that will affect the water and sediment management of the river, its floodplain, and bay, thus varying approaches for restoration.
Immunostimulatory and antioxidant activities of the selenized polysaccharide from edible Grifola frondosa
Authors: Li Qian , Zhu Linfei , Qi Xingpu , Zhou Ting , Li Yonglian , Cai Mingjie , Yan Yuting , Qian Jian‐Ya , Peng Daxin
Published: February 2022

Grifola frondosa polysaccharide (GFP2) was extracted and purified by anion‐exchange chromatography. A selenized G. frondosa polysaccharide, SeGFP2, was modified in selenylation by nitric acid–sodium selenite (HNO3‐Na2SeO3) method. Structural features were investigated, and the lymphocyte proliferation and antioxidant activities were compared taking GFP2 as control. SeGFP2 with a molecular weight of 2.12 × 104 Da was composed of mannose, glucose, and galactose with a ratio of 3.5:11.8:1.0. A typical absorption of selenium ester was observed in SeGFP2 molecule. SeGFP2 was proposed as a branched polysaccharide, which consisted of 1,3‐D‐Glcp, 1,6‐D‐Glcp, 1,4,6‐D‐Galp, and 1,3,6‐D‐Manp. SeGFP2 showed a linear filamentous structure with some branches. SeGFP2 could significantly promote T‐ or B‐lymphocyte proliferation and the enhancement was higher than GFP2. The in vitro antioxidant activities of SeGFP2 were more potent than GFP2. These present data suggested that selenylation could significantly improve the lymphocyte proliferation and in vitro antioxidant activities of GFP2.
Fusion‐associatedcarcinomas of the breast: Diagnostic, prognostic, and therapeutic significance
Authors: Loo Suet Kee , Yates Megan E. , Yang Sichun , Oesterreich Steffi , Lee Adrian V. , Wang Xiao‐Song
Published: February 2022

Recurrent gene fusions comprise a class of viable genetic targets in solid tumors that have culminated several recent breakthrough cancer therapies. Their role in breast cancer, however, remains largely underappreciated due to the complexity of genomic rearrangements in breast malignancy. Just recently, we and others have identified several recurrent gene fusions in breast cancer with important clinical and biological implications. Examples of the most significant recurrent gene fusions to date include (1)ESR1::CCDC170gene fusions in luminal B and endocrine‐resistant breast cancer that exert oncogenic function via modulating the HER2/HER3/SRC Proto‐Oncogene (SRC) complex, (2)ESR1exon 6 fusions in metastatic disease that drive estrogen‐independent estrogen‐receptor transcriptional activity, (3)BCL2L14::ETV6fusions in a more aggressive form of the triple‐negative subtype that prime epithelial–mesenchymal transition and endow paclitaxel resistance, (4) theETV6::NTRK3fusion in secretory breast carcinoma that constitutively activates NTRK3 kinase, (5) the oncogenicMYB‐NFIBfusion as a genetic driver underpinning adenoid cystic carcinomas of the breast that activates MYB Proto‐Oncogene (MYB) pathway, and (6) the NOTCH/microtubule‐associated serine–threonine (MAST) kinase gene fusions that activate NOTCH and MAST signaling. Importantly, these fusions are enriched in more aggressive and lethal breast cancer presentations and appear to confer therapeutic resistance. Thus, these gene fusions could be utilized as genetic biomarkers to identify patients who require more intensive treatment and surveillance. In addition, kinase fusions are currently being evaluated in breast cancer clinical trials and ongoing mechanistic investigation is exposing therapeutic vulnerabilities in patients with fusion‐positive disease.
Migration of carbon dioxide in sandstone under various pressure/temperature conditions: From experiment to simulation
Authors: Xu Liang , Li Qi , Myers Matthew , White Cameron , Cao Xiaomin
Published: February 2022

The pressure and temperature of a target CO2 storage reservoir can significantly affect the migration and relative permeability characteristics which can ultimately determine the carbon storage capacity and storage integrity of target formations. To understand these impacts, a CO2 core‐flooding experiment was conducted on a brine‐saturated sandstone containing a single clay interlayer perpendicular to the flow direction at a temperature of 313 K and a pressure of 8 MPa and the fluid distribution was monitored by a high‐resolution X‐ray computed tomography (X‐CT) scanner. Further, a one‐dimensional model was established to reproduce the CO2 flow behavior inside the sample under the same experimental condition and then the model was extended to different temperatures (313 and 350 K) and pressures (6, 8, 12, and 17.4 MPa). The experimental results show that the CO2 preferentially created high‐CO2‐saturation flow pathways which then expanded until they were large enough to transport the CO2 at the prescribed flow rate. The sub‐core scale heterogeneity also had significant effects on the CO2 migration, forming a barrier to downstream flow. The simulation results show that at a given temperature, the CO2 front migration velocity decreased with increasing reservoir pressure while the CO2 saturation along the pathways increased. Comparing simulations when the reservoir pressure was the same, the front‐migration velocity increased with increasing temperature, and the CO2 saturation along the pathways decreased. Meanwhile, the influence of temperature and pressure on CO2 saturation distribution was more evident in the parts of the core with high residual brine saturation. © 2022 Society of Chemical Industry and John Wiley & Sons, Ltd.
The roles of microglia and astrocytes in phagocytosis and myelination: Insights from the cuprizone model of multiple sclerosis
Authors: Sen Monokesh K. , Mahns David A. , Coorssen Jens R. , Shortland Peter J.
Published: February 2022

In human demyelinating diseases such as multiple sclerosis (MS), an imbalance between demyelination and remyelination can trigger progressive degenerative processes. The clearance of myelin debris (phagocytosis) from the site of demyelination by microglia is critically important to achieve adequate remyelination and to slow the progression of the disease. However, how microglia phagocytose the myelin debris, and why clearance is impaired in MS, is not fully known; likewise, the role of the microglia in remyelination remains unclear. Recent studies using cuprizone (CPZ) as an animal model of central nervous system demyelination revealed that the up‐regulation of signaling proteins in microglia facilitates effective phagocytosis of myelin debris. Moreover, during demyelination, protective mediators are released from activated microglia, resulting in the acceleration of remyelination in the CPZ model. In contrast, inadequate microglial activation or recruitment to the site of demyelination, and the production of toxic mediators, impairs remyelination resulting in progressive demyelination. In addition to the microglia‐mediated phagocytosis, astrocytes play an important role in the phagocytic process by recruiting microglia to the site of demyelination and producing regenerative mediators. The current review is an update of these emerging findings from the CPZ animal model, discussing the roles of microglia and astrocytes in phagocytosis and myelination.
Longitudinal intravital imaging of cerebral microinfarction reveals a dynamic astrocyte reaction leading to glial scar formation
Authors: Lee Jingu , Kim Joon‐Goon , Hong Sujung , Kim Young Seo , Ahn Soyeon , Kim Ryul , Chun Heejung , Park Ki Duk , Jeong Yong , Kim Dong‐Eog , Lee C. Justin , Ku Taeyun , Kim Pilhan
Published: February 2022

Cerebral microinfarct increases the risk of dementia. But how microscopic cerebrovascular disruption affects the brain tissue in cellular‐level are mostly unknown. Herein, with a longitudinal intravital imaging, we serially visualized in vivo dynamic cellular‐level changes in astrocyte, pericyte and neuron as well as microvascular integrity after the induction of cerebral microinfarction for 1 month in mice. At day 2–3, it revealed a localized edema with acute astrocyte loss, neuronal death, impaired pericyte‐vessel coverage and extravascular leakage of 3 kDa dextran (but not 2 MDa dextran) indicating microinfarction‐related blood–brain barrier (BBB) dysfunction for small molecules. At day 5, the local edema disappeared with the partial restoration of microcirculation and recovery of pericyte‐vessel coverage and BBB integrity. But brain tissue continued to shrink with persisted loss of astrocyte and neuron in microinfarct until 30 days, resulting in a collagen‐rich fibrous scar surrounding the microinfarct. Notably, reactive astrocytes expressing glial fibrillary acidic protein (GFAP) appeared at the peri‐infarct area early at day 2 and thereafter accumulated in the peri‐infarct until 30 days, inducing glial scar formation in cerebral cortex. Our longitudinal intravital imaging of serial microscopic neurovascular pathophysiology in cerebral microinfarction newly revealed that astrocytes are critically susceptible to the acute microinfarction and their reactive response leads to the fibrous glial scar formation.
Hospital‐associated deconditioning: Not only physical, but also cognitive
Authors: Chen Yaohua , Almirall‐Sánchez Arianna , Mockler David , Adrion Emily , Domínguez‐Vivero Clara , Romero‐Ortuño Román
Published: February 2022

Introduction

Hospital‐associated deconditioning (HAD) or post‐hospital syndrome is well recognized as reduced functional performance after an acute hospitalization. Recommendations for the management of HAD are still lacking, partly due to a poor understanding of the underlying processes. We aimed to review existing data on risk factors, pathophysiology, measurement tools, and potential interventions.

Materials and methods

We conducted a systematic review from bibliographical databases in English, Spanish and French with keywords such as ‘post‐hospitalization syndrome’ or ‘deconditioning’. We selected studies that included people aged 60 years or older. Three researchers independently selected articles and assessed their quality.

Results

From 4421 articles initially retrieved, we included 94 studies. Most were related to risk factors, trajectories and measures, and focused on the physical aspects of deconditioning. Risk factors for HAD included age, nutritional status, mobility, and pre‐admission functional status, but also cognitive impairment and depression. Regarding interventions, almost all studies were devoted to physical rehabilitation and environmental modifications. Only one study focused on cognitive stimulation.

Discussion

In the last decade, studies on HAD have mostly focused on the physical domain. However, neurological changes may also play a role in the pathophysiology of HAD. Beyond physical interventions, cognitive rehabilitation and neurological interventions should also be evaluated to improve deconditioning prevention and treatment in the hospital setting.
Quantitative susceptibility mapping shows lower brain iron content in children with attention‐deficit hyperactivity disorder
Authors: Tang Shilong , Zhang Guanping , Ran Qiying , Nie Lisha , Liu Xianfan , Pan Zhengxia , He Ling
Published: February 2022

To investigate the feasibility of quantitative susceptibility mapping in children with attention‐deficit hyperactivity disorder (ADHD), 53 children with ADHD aged 5–16 years were prospectively selected as the study group and 49 healthy children matched with age and gender were selected as the control group. All children underwent magnetic resonance imaging conventional sequence, 3D‐T1, and enhanced T2*‐weighted magnetic resonance angiography (ESWAN) sequence scanning. The iron content of brain regions was obtained through software postprocessing, and the iron content of brain regions of children with ADHD and healthy children was compared and analyzed to find out the characteristics of the iron content of brain regions of children with ADHD. The iron content in frontal lobe, globus pallidus, caudate nucleus, substantia nigra, putamen, and hippocampus of children with ADHD was lower than that of healthy children (p < .05). There was no significant difference in the content of iron in the left and right brain regions of children with ADHD (p > .05). The volume of frontal lobe and hippocampus of children with ADHD was lower than that of healthy children (p < .05). Iron content in brain areas such as globus pallidus, caudate nucleus, hippocampus, and putamen could distinguish children with ADHD (Area under curve [AUC] > 0.5, p < .05). Quantitative susceptibility mapping showed decreased iron content in some brain regions of children with ADHD.
Debt‐to‐GDP changes and the great recession: European Periphery versus European Core
Authors: Agoraki Maria‐Eleni K. , Kardara Stella , Kollintzas Tryphon , Kouretas Georgios P.
Published: February 2022

In this paper, we use simple accounting schemes and counterfactual experiments, to compare the sources of changes in the public debt to GDP ratio across countries of the European Periphery (Greece, Ireland, Italy, Portugal and Spain), the European Core (Germany and France) and the other G7 countries (Canada, Japan, the United Kingdom and the United States), in two periods—2000–2007 and 2008–2015. In general, Debt‐to‐GDP ratio rose in all countries in the latter period. But the effects of total or primary fiscal deficits, inflation and real growth on the respective Debt‐to‐GDP ratio changes were different across countries in both periods. In the European Core, Ireland and the Anglo‐Saxon countries, successful countercyclical fiscal policies, tended to lower Debt‐to‐GDP ratio. However, in the other European Periphery countries and Japan, unsuccessful countercyclical policies, had the opposite effect. Since in the Euro Area (EA), monetary policy is common and fiscal policies were restricted by rules, this development suggests that differences in shock propagation mechanisms were important drivers of the observed differences in the behaviour of Debt‐to‐GDP ratio between the European Core and the EA Periphery, except Ireland. An implication of this result is that the recently announced EU transfers to the EA Periphery tied up to incentives to improve economic efficiency, seem to be the right policies to ameliorate the effects of the recession brought about by the various social distancing measures to fight the COVID‐19 pandemic, without increasing the Debt‐to‐GDP ratios of these countries.
Changes in carabid diversity indicate successful restoration of riparian habitats
Authors: Sprössig Claudia , Dziock Frank , Buchholz Sascha
Published: February 2022

Natural rivers offer riparian habitats to many highly specialised, rare, and endangered insect species and are extremely important for ecosystem services. In the past, these ecosystems have been heavily degraded by anthropogenic use and run the risk of losing their favourable ecological conditions. For this reason, restoration measures are urgently needed and strongly demanded politically as well as legally, for instance, through the European Union Water Framework Directive. This is also important because nowadays, we are confronted with increasing insect declines. Using a Before‐After‐Control‐Impact approach, we studied the effects of a riverbank restoration (complete removal of a large gravel embankment) on carabid assemblages of riparian habitats along the Mulde River in central Germany in 2017 and 2019. We collected 86 species in three site types (managed, natural, and restored) by pitfall trapping and found numerous species of conservation concern. Our analyses showed that the percentage of species of conservation concern was significantly higher after restoration in restored compared to managed sites. Furthermore, after restoration, the percentage of indicator species for natural sites increased significantly in restored sites while the abundance of indicator species characteristic for managed sites decreased in these sites. Species assemblage composition significantly changed in response to restoration approaching near‐natural conditions. The creation of habitat mosaics with open gravel and sand patches as well as the re‐establishment of river dynamics were likely the most significant drivers for restoration success. We were able to show how important the restoration of riparian habitats is to promote populations of endangered, rare, and specialised species. Our results highlight that positive effects of a river restoration measure can be observed after a relatively short time. Ground beetles can thus be viewed as early indicators for restoration success, but we see a need for long‐term monitoring to evaluate long‐term effects reliably.
The effects of pedestrian gestures on driver yielding at crosswalks: A systematic replication
Authors: Myers Cassidy , Zane Thomas , Van Houten Ron , Francisco Vincent T
Published: February 2022

Applied research on decreasing pedestrian injuries often focuses on how to increase driver yielding behavior but rarely studies what pedestrians can do to increase their safety. There is a lack of empirical research focusing on how pedestrians can effectively signal their need to cross the street when there is no traffic light directing the pedestrian and oncoming traffic. As a replication and extension of Crowley‐Koch et al. (2011), this study examined the effects of two pedestrian gestures, an extended arm and raised hand, on driver yielding behavior at 3 crosswalks in Oklahoma City. Research assistants implemented gestures prior to crossing the street as cars approached the crosswalk. Data were collected on the percentage of drivers yielding to the pedestrian. Both pedestrian gestures increased driver yielding across all 3 sites when compared to no gesture. Results were discussed in terms of future research and practical solutions towards increasing pedestrian safety.
Evaluation of the genotoxic potential of protoporphyrin IX and the safety of a protoporphyrin IX‐rich algal biomass
Authors: Murbach Timothy S. , Glávits Róbert , Moghadam Maragheh Niloofar , Endres John R. , Hirka Gábor , Goodman Richard E. , Lu Guihua , Vértesi Adél , Béres Erzsébet , Pasics Szakonyiné Ilona
Published: February 2022

Chlamydomonas reinhardtii is a nonpathogenic, nontoxigenic green algae used as a sustainable source of protein in foods. In order to mimic meat‐like qualities, a strain rich in protoporphyrin IX (PPIX), an endogenous heme/chlorophyll precursor, was developed using an evolution and selection strategy, and investigations were carried out to evaluate the safety of the novel strain, C. reinhardtii (red), strain TAI114 (TAI114). Digestibility and proteomic evaluations were conducted to determine whether any potentially allergenic or toxic proteins occurred as the result of the mutation process. The genotoxic potential of pure PPIX was evaluated using a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, and an in vivo mammalian micronucleus test. Finally, the novel TAI114 biomass was evaluated for general toxicity and identification of target organs in a 90‐day repeated‐dose oral toxicity study in rats. All proteins were rapidly degraded in pepsin at pH 2.0 suggesting low allergenic potential. The proteomic evaluation indicated that TAI114 biomass contains typical C. reinhardtii proteins. PPIX was unequivocally negative for genotoxic potential and no target organs or adverse effects were observed in rats up to the maximum feasible dose of 4000 mg/kg bw/day TAI114 biomass, which was determined to be the no‐observed‐adverse‐effect‐level (NOAEL). These results support the further development and risk characterization of TAI114 biomass as a novel ingredient for use in the meat analogue category of food.
Elucidating the combinatorial effect of substrate stiffness and surface viscoelasticity on cellular phenotype
Authors: Chester Daniel , Lee Veronica , Wagner Paul , Nordberg Matthew , Fisher Matthew B. , Brown Ashley C.
Published: February 2022

Cells maintain tensional homeostasis by monitoring the mechanics of their microenvironment. In order to understand this mechanotransduction phenomenon, hydrogel materials have been developed with either controllable linear elastic or viscoelastic properties. Native biological tissues, and biomaterials used for medical purposes, often have complex mechanical properties. However, due to the difficulty in completely decoupling the elastic and viscous components of hydrogel materials, the effect of complex composite materials on cellular responses has largely gone unreported. Here, we characterize a novel composite hydrogel system capable of decoupling and individually controlling both the bulk stiffness and surface viscoelasticity of the material by combining polyacrylamide (PA) gels with microgel thin films. By taking advantage of the high degree of control over stiffness offered by PA gels and viscoelasticity, in terms of surface loss tangent, of microgel thin films, it is possible to study the influence that bulk substrate stiffness and surface loss tangent have on complex fibroblast responses, including cellular and nuclear morphology and gene expression. This material system provides a facile method for investigating cellular responses to complex material mechanics with great precision and allows for a greater understanding of cellular mechanotransduction mechanisms than previously possible through current model material platforms.
Magnesium promotes osteogenesis via increasing OPN expression and activating CaM/CaMKIV/CREB1 pathway
Authors: Hou Peng , Sun Yu , Yang Weichao , Wu Hongliu , Sun Luyuan , Xiu Xinjie , Xiu Chaoyang , Zhang Xiaonong , Zhang Wen
Published: February 2022

Magnesium (Mg) based alloy has been used as a biodegradable implant for fracture repair with considerable efficacy, and it has been proved that magnesium ion (Mg2+), one of the degradation products, could stimulate osteogenesis. Here, we investigated the osteogenesis property of magnesium both in vitro and in vivo, and to identify the cellular and molecular mechanisms that mediate these effects. Results showed that magnesium exerts a dose‐dependent increase in the proliferation of MC3T3 and MG63 cells, and in the expression of osteopontin (OPN), a promising biomarker of osteogenesis. Subsequently, the protein–protein interaction (PPI) network analysis showed the interactions between calmodulin (CaM) and calmodulin‐dependent protein kinase (CaMK) and CREB1. The ratio of p‐CaMKIV/CaMKIV and p‐CREB1/CREB were increased at protein level in MC3T3 and MG63 cells after treatment with Mg2+. Dual‐luciferase reporter gene assay showed that p‐CREB1 could directly bind to OPN promoter and up‐regulate the transcription of OPN after nuclear entry. Meanwhile, the expression of OPN and p‐CREB1, which increased after Mg2+ treatment, was down‐regulated by sh‐CaMKIV or sh‐CREB1. Moreover, the mineralized deposit and expression of OPN were reduced after treatment with an inhibitor of CaMKIV, KN93. In addition, massive cavities in the cortical bone around the Mg screw were showed in vivo after injection of KN93. These data indicated that the osteogenic effect of Mg is related to the activation OPN through CaM/CaMKIV/CREB1 signaling pathway.
Independent gradient model based on Hirshfeld partition: A new method for visual study of interactions in chemical systems
Authors: Lu Tian , Chen Qinxue
Published: February 2022

The powerful independent gradient model (IGM) method has been increasingly popular in visual analysis of intramolecular and intermolecular interactions in recent years. However, we frequently observed that there is an evident shortcoming of IGM map in graphically studying weak interactions, that is its isosurfaces are usually too bulgy; in these cases, not only the graphical effect is poor, but also the color on some areas on the isosurfaces is inappropriate and may lead to erroneous analysis conclusions. In addition, the IGM method was originally proposed based on promolecular density, which is quite crude and does not take actual electronic structure into account. In this article, we propose an improvement version of IGM, namely IGM based on Hirshfeld partition of molecular density (IGMH), which replaces the free‐state atomic densities involved in the IGM method with the atomic densities derived by Hirshfeld partition of actual molecular electron density. This change makes IGM have more rigorous physical background. A large number of application examples in this article, including molecular and periodic systems, weak and chemical bond interactions, fully demonstrate the important value of IGMH in intuitively understanding interactions in chemical systems. Comparisons also showed that the IGMH usually has markedly better graphical effect than IGM and overcomes known problems in IGM. Currently IGMH analysis has been supported in our wavefunction analysis code Multiwfn (http://sobereva.com/multiwfn). We hope that IGMH will become a new useful method among chemists for exploring interactions in wide variety of chemical systems.
Chemical repair of damaged leucine and tryptophane by thiophenols at close to diffusion‐controlled rates: Mechanisms and kinetics
Authors: Carreon‐Gonzalez Mirzam , Muñoz‐Rugeles Leonardo , Vivier‐Bunge Annik , Alvarez‐Idaboy Juan Raul
Published: February 2022

Thiophenols are chemical species with multiple desirable biological properties, including their primary and secondary antioxidant capacity. In this work, the repairing antioxidant activity of eight different thiophenols has been investigated for damaged leucine and tryptophane. The investigation was carried out employing quantum mechanical and transition state methods to calculate the thermodynamic and kinetic data of the reactions involved, while simulating the biological conditions at physiological pH and aqueous and lipidic medium. The analysis of the atomic charges and the spin densities at each of the points on the potential energy surface was the tool that allowed the elucidation of the reaction mechanisms through which thiophenols repair the oxidative damage caused to the amino acids leucine and tryptophan. It was found that thiophenols can repair leucine via a hydrogen atom transfer mechanism in a manner which is similar to the one used by glutathione to repair the carbon‐centered radicals of guanosine. In addition, thiophenols can also restore tryptophane, a nitrogen‐centered radical, via proton‐coupled electron transfer and single electron transfer mechanisms. Moreover, both processes occur at close to diffusion‐controlled rates.
The lncRNA HOXA11‐AS acts as a tumor promoter in breast cancer through regulation of the miR‐125a‐5p/TMPRSS4 axis
Authors: Xu Yunfeng , Ren Zhiyao , Wang Xin , Ren Min
Published: February 2022

Background

Long non‐coding RNAs (lncRNAs) play vital roles in tumorigenesis. Here, we explored how lncRNA HOXA11‐AS functions in the progression of breast cancer (BC).

Methods

HOXA11‐AS and miR‐125a‐5p levels were measured by a quantitative real‐time polymerase chain reaction, whereas western blotting determined TMPRSS4 levels in BC tumor tissues, adjacent normal tissues and BC cell lines. The roles of HOXA11‐AS, miR‐125a‐5p and TMPRSS4 in BC proliferation were investigated using cell counting kit‐8, colony formation and flow cytometry assays, whereas scratch and transwell assays were used to measure metastasis. RNA pull‐down assays and dual‐luciferase assays assessed direct interactions between HOXA11‐AS and miR‐125a‐5p. The effects of HOXA11‐AS in vivo were investigated in a BC xenograft model.

Results

HOXA11‐AS was upregulated in tumor tissues of 56 BC patients compared to adjacent non‐tumor tissues, with high levels being associated with worse overall survival. Silencing of HOXA11‐AS inhibited the proliferation and metastasis of BC cells, leading to cell cycle arrest in G0/G1 and induction of apoptosis. We identified miR‐125a‐5p as a target of HOXA11‐AS, with miR‐125a‐5p inhibitors partially restoring the reduction of cell proliferation and metastasis induced by HOXA11‐AS silencing. We also determined that miR‐125a‐5p targeted TMPRSS4 mRNA, with HOXA11‐AS knockdown and miR‐125a‐5p mimics suppressing TMPRSS4. Overexpression of TMPRSS4 partially compensated for the reduction of cell proliferation and metastasis induced by HOXA11‐AS silencing. Finally, we confirmed the mechanism of HOXA11‐AS in the regulation of tumorigenesis in the mouse model.

Conclusions

HOXA11‐AS regulates the tumorigenic ability of BC via the miR‐125a‐5p/TMPRSS4 axis. This provides insights for regulatory mechanisms involved in BC progression, and may enable new treatment strategies in the clinical setting.
Direct replacement of oral sodium benzoate with glycerol phenylbutyrate in children with urea cycle disorders
Authors: Yeo Mildrid , Rehsi Preeya , Dorman Megan , Grunewald Stephanie , Baruteau Julien , Chakrapani Anupam , Footitt Emma , Prunty Helen , McSweeney Melanie
Published: February 2022

Long‐term management of urea cycle disorders (UCDs) often involves unlicensed oral sodium benzoate (NaBz) which has a high volume and unpleasant taste. A more palatable treatment is licenced and available (glycerol phenylbutyrate [GPB], Ravicti) but guidance on how to transition patients from NaBz is lacking. A retrospective analysis of clinical and biochemical data was performed for eight children who transitioned from treatment with a single ammonia scavenger, NaBz, to GPB at a single metabolic centre; UCDs included arginosuccinic aciduria (ASA) (n = 5), citrullinaemia type 1 (n = 2) and carbamoyl phosphate synthetase I deficiency (CPS1) (n = 1). Patients transitioned either by gradual transition over 1–2 weeks (n = 3) or direct replacement of NaBz with GPB (n = 5). Median initial dose of GPB was 8.5 mL/m2/day based on published product information; doses were revisited subsequently in clinic and titrated individually (range 4.5–11 mL/m2/day). Pre‐transition and post‐transition mean ammonia levels were 37 μmol/L (SD 28 μmol/L) and 29 μmol/L (SD 22 μmol/L), respectively (p = 0.09), and mean glutamine levels were 664 μmol/L (SD 225 μmol/L) and 598 μmol/L (SD 185 μmol/L), respectively (p = 0.24). There were no reductions in levels of branched chain amino acids. No related adverse drug reactions were reported. Patients preferred GPB because of its lower volume and greater palatability. Direct replacement of NaBz with GPB maintained metabolic control and was simple for the health service and patients to manage. A more cautious approach with additional monitoring would be warranted in brittle patients and patients whose ammonia levels are difficult to control.
Neurotransmission and neuromodulation systems in the learning and memory network of Octopus vulgaris
Authors: Stern‐Mentch Naama , Bostwick Gabrielle Winters , Belenky Michael , Moroz Leonid , Hochner Binyamin
Published: February 2022

The vertical lobe (VL) in the octopus brain plays an essential role in its sophisticated learning and memory. Early anatomical studies suggested that the VL is organized in a “fan‐out fan‐in” connectivity matrix comprising only three morphologically identified neuron types; input axons from the median superior frontal lobe (MSFL) innervating en passant millions of small amacrine interneurons (AMs), which converge sharply onto large VL output neurons (LNs). Recent physiological studies confirmed the feedforward excitatory connectivity; a glutamatergic synapse at the first MSFL‐to‐AM synaptic layer and a cholinergic AM‐to‐LNs synapse. MSFL‐to‐AMs synapses show a robust hippocampal‐like activity‐dependent long‐term potentiation (LTP) of transmitter release. 5‐HT, octopamine, dopamine and nitric oxide modulate short‐ and long‐term VL synaptic plasticity. Here, we present a comprehensive histolabeling study to better characterize the neural elements in the VL. We generally confirmed glutamatergic MSFLs and cholinergic AMs. Intense labeling for NOS activity in the AMs neurites were in‐line with the NO‐dependent presynaptic LTP mechanism at the MSFL‐to‐AM synapse. New discoveries here reveal more heterogeneity of the VL neurons than previously thought. GABAergic AMs suggest a subpopulation of inhibitory interneurons in the first input layer. Clear γ‐amino butyric acid labeling in the cell bodies of LNs supported an inhibitory VL output, yet the LNs co‐expressed FMRFamide‐like neuropeptides, suggesting an additional neuromodulatory role of the VL output. Furthermore, a group of LNs was glutamatergic. A new cluster of cells organized as a “deep nucleus” showed rich catecholaminergic labeling and may play a role in intrinsic neuromodulation. In‐situ hybridization and immunolabeling allowed characterization and localization of a rich array of neuropeptides and neuromodulators, likely involved in reward/punishment signals. This analysis of the fast transmission system, together with the newly found cellular elements, help integrate behavioral, physiological, pharmacological and connectome findings into a more comprehensive understanding of an efficient learning and memory network.
The Ensemble Oceanic Niño Index
Authors: Webb Eric J. , Magi Brian I.
Published: February 2022

We describe a new El Niño–Southern Oscillation (ENSO) index that we call the Ensemble Oceanic Niño Index (Ensemble ONI). Ensemble ONI uses monthly sea surface temperature (SST) anomalies in the Niño3.4 region from 32 input SST datasets as the basis for the ensemble, and our new monthly ENSO index extends from the present back to the year 1850. We use the input datasets to quantify the uncertainty in the monthly index values. The uncertainty is calculated from datasets that are not completely independent from each other, but we use other estimates of uncertainty in SST, well‐documented historical ENSO events, a detailed consideration of literature‐based definitions of ENSO events, and proxy‐based determinations of past ENSO events, to show that our uncertainty estimate from the ensemble of input datasets is comparable with other studies both in terms of average magnitude and the time‐varying trend. Similar to past research, we find that ENSO events occur every 4–5 years on average, and there have been six “Super” El Niños (1877–1878, 1888–1889, 1972–1973, 1982–1983, 1997–1998, 2015–2016) that statistically rise above all other El Niños since 1850. Finally, the time span of our work shows that El Niño events were most intense at ends of both the 19th century and the 20th century, with a lull in the mid‐1900s, corroborating previous instrumental, written, and proxy records.
Climatology and extreme cases of sea‐effect snowfall on the southern Baltic Sea coast
Authors: Bednorz Ewa , Czernecki Bartosz , Tomczyk Arkadiusz M.
Published: February 2022

Heavy snowfall events of possible sea‐effect origin, occurring on the southern Baltic Sea coast, are described in this study. The analysed region is not very snowy, with an average of 40 days with snow cover in the winter season and a mean maximum snow depth of 8–12 cm. Twenty‐five snowfall events were selected using the threshold of 20 cm/2 days (i.e., 20 cm of snow depth increase during 2 days), and the synoptic climatology, as well as triggering factors of their occurrence, were defined. The bipolar pattern of sea level pressure with a high‐pressure over Scandinavia and a low‐pressure system southward of it was identified as favourable for sea‐effect snowfall on the southern Baltic Sea coast. This pressure field, causing northeastern circulation in the lower troposphere, brings cold air masses over the relatively warm sea basin, and the negative anomalies of air temperature at 850 hPa geopotential level, amounting to −9°C, encompass Scandinavia, as well as central and northeastern Europe. This makes the temperature difference between the air at the 850 hPa geopotential height and the sea surface exceeding 15°C. This large temperature difference establishes favourable conditions for convection in cold air masses, which become unstable while crossing over the warm sea. The formed clouds give snowfall in the coastal areas. In the further part of the study, three sea‐effect snowfall cases were chosen for detailed analysis, including atmospheric sounding, radar and satellite images, air parcel backward trajectories, and synoptic maps. They reveal high‐pressure wedges associated with low air temperature over Scandinavia and northern airflow over the Baltic Sea. The wind direction and the temperature of air masses are key components in the occurrence of sea‐effect snowfall, and global warming conditions seem to reduce the frequency of snow events over the Polish Baltic Sea coast.
Highly efficient enrichment of intact phosphoproteins by a cadmium ion‐based co‐precipitation strategy
Authors: Li Jiangfeng , Fan Chongyuan , Yao Yating , Liu Zhaochen , Li Fangfang , Jiang Binghua
Published: February 2022

Selective separation and enrichment of phosphoproteins are essential for understanding their important functions in almost all cellular processes. Here, taking advantage of the feature that cadmium ion (Cd2+) has an overwhelming preference for phosphates, we developed a robust and simple Cd2+ co‐precipitation strategy for the selective isolation of intact phosphoproteins. After evaluating the feasibility of Cd2+ in phosphoprotein precipitation, we compared the washing protocols for the removal of non‐specific binding proteins and then used the best‐performing protocol for the isolation of phosphoproteins from different complex samples. It was found that phosphoproteins can be specifically enriched from artificial protein mixtures containing α‐casein, β‐casein, and bovine serum albumin or plasma, in which bovine serum albumin or plasma were served as interferences with very high molar ratios. Applying this method to enrich phosphoproteins from complex cell lysates, a high specificity was confirmed by western blotting analysis with a phosphoprotein‐specific kit. Finally, we successfully applied this method to the purification of caseins from drinking milk, highlighting its potential application in the studies where purified phosphoproteins were required. In a word, this Cd2+ co‐precipitation method enables universal and effective capture, enrichment, and detection of intact phosphoproteins, making it a powerful tool for the comprehensive analysis of the phosphoproteome.