bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractIn 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

AbstractCerebral 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

AbstractIntroductionHospital‐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 methodsWe 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.ResultsFrom 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.DiscussionIn 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

AbstractTo 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

AbstractIn 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

AbstractNatural 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.
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

AbstractChlamydomonas 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

AbstractCells 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

AbstractMagnesium (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

AbstractThe 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

AbstractThiophenols 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

AbstractBackgroundLong non‐coding RNAs (lncRNAs) play vital roles in tumorigenesis. Here, we explored how lncRNA HOXA11‐AS functions in the progression of breast cancer (BC).MethodsHOXA11‐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.ResultsHOXA11‐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.ConclusionsHOXA11‐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

AbstractLong‐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.