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Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

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Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li Department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden Department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Physiology and Pharmacology Karolinska InstitutetStockholmSweden Department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA Department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

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Neural Regeneration Research 2025年第1期20卷 41-53页

作者： Alessio Canovai Pete A.Williams Department of Biology University of PisaPisaItaly Department of Clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

Neuroscience at Karolinska Institutet,a medical university in stockholm

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Journal of Translational Neuroscience 2016年第1期1卷 60-63页

作者： Gunnar Grant Department of Neuroscience Retzius vag 8Karolinska InstitutetS-171 77StockholmSweden

Karolinska Institutet is one of the founding members of the International Alliance for Translational Neuro-science ,IATN. This alliance was established in Beijing in 2012 and it presently includes seven members world-wide. Karolinska Institutet has a long tradition in research on the nervous system. Early on it was mainly represented by the Department of Neurophysiology and the Nobel Laureate Ragnar Granit, and the Department of Physiology, where Ulf von Euler, also a Nobel Laureate,carried out pioneering work on catecholamines, substance P and prostaglandins （ see Grant G ： The Nobel Prizes in the Field of Neuroscience which was published in the same issue）.

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Tectonic calibrations in molecular dating

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Current Zoology 2011年第1期57卷 116-124页

作者： Ullasa KODANDARAMAIAH Department of Zoology Stockholm University Stockholm 10691 Sweden

Molecular dating techniques require the use of calibrations, which are usually fossil or geological vicariance-based. Fossil calibrations have been criticised because they result only in minimum age estimates. Based on a historical biogeographic perspective, I suggest that vicariance-based calibrations are more dangerous. Almost all analytical methods in historical biogeog- raphy are strongly biased towards inferring vicariance, hence vicariance identified through such methods is unreliable. Other studies, especially of groups found on Gondwanan fragments, have simply assumed vicariance. Although it was previously be- lieved that vicariance was the predominant mode of speciation, mounting evidence now indicates that speciation by dispersal is common, dominating vicaziance in several groups. Moreover, the possibility of speciation having occurred before the said geo- logical event cannot be precluded. Thus, geological calibrations can under- or overestimate times, whereas fossil calibrations al- ways result in minimum estimates. Another major drawback of vicariant calibrations is the problem of circular reasoning when the resulting estimates are used to infer ages of biogeographic events. I argue that fossil-based dating is a superior alternative to vicariance, primarily because the strongest assumption in the latter, that speciation was caused by the said geological process, is more often than not the most tenuous. When authors prefer to use a combination of fossil and vicariant calibrations, one suggestion is to report results both with and without inclusion of the geological constraints. Relying solely on vicariant calibrations should be strictly avoided

关键词： Molecular dating Calibrations Fossils Vicariance Paleontological Relaxed clock

Predicting Amazon customer reviews with deep confidence using deep learning and conformal prediction

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Journal of Management Analytics 2022年第1期9卷 1-16页

作者： Ulf Norinder Petra Norinder Department of Computer and Systems Sciences Stockholm UniversityKistaSweden stockholm Business School Stockholm UniversityStockholmSweden

In this investigation,we have shown that the combination of deep learning,including natural language processing,and conformal prediction results in highly predictive and efficient temporal test set sentiment estimates for 12 categories of Amazon product reviews using either in-category predictions,*** model and the test set are from the same review category or cross-category predictions,*** a model of another review category for predicting the test *** similar results from in-and cross-category predictions indicate high degree of generalizability across product review *** investigation also shows that the combination of deep learning and conformal prediction gracefully handles class imbalances without explicit class balancing measures.

关键词： Amazon customer reviews machine learning conformal prediction deep learning natural language processing temporal test sets

Host plant choice in the comma butterfly-larval choosiness may ameliorate effects of indiscriminate oviposition

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Insect Science 2014年第4期21卷 499-506页

作者： Gabriella Gamberale-Stille Lina Soderlind Niklas Janz Soren Nylin Department of Zoology Stockholm University 106 92 Stockholm Sweden

In most phytophagous insects, the larval diet strongly affects future fitness and in species that do not feed on plant parts as adults, larval diet is the main source of nitrogen. In many of these insect-host plant systems, the immature larvae are considered to be fully dependent on the choice of the mothers, who, in turn, possess a highly developed host recognition system. This circumstance allows for a potential mother-offspring conflict, resulting in the female maximizing her fecundity at the expense of larval performance on suboptimal hosts. In two experiments, we aimed to investigate this relationship in the polyphagous comma butterfly, Polygonia c-album, by comparing the relative acceptance of low- and medium-ranked hosts between females and neonate larvae both within individuals between life stages, and between mothers and their offspring. The study shows a variation between females in oviposition acceptance of low-ranked hosts, and that the degree of acceptance in the mothers correlates with the probability of acceptance of the same host in the larvae. We also found a negative relationship between stages within individuals as there was a higher acceptance of lower ranked hosts in females who had abandoned said host as a larva. Notably, however, neonate larvae of the comma butterfly did not unconditionally accept to feed from the least favorable host species even when it was the only food source. Our results suggest the possibility that the disadvantages associated with a generalist oviposition strategy can be decreased by larval participation in host plant choice.

关键词： host plant choice insect-host plant interaction mobility oviposition behav-ior parent-offspring conflict specialization

Sustainability of microporous polymers and their applications

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Science China Chemistry 2017年第8期60卷 1033-1055页

作者： Tamara L.Church Alma Berenice Jasso-Salcedo Fredrik Bjrnerbck Niklas Hedin Department of Materials and Environmental Chemistry Stockholm University SE-106 91 Stockholm Sweden

Microporous polymers(MPs) are studied for their intriguing chemistry and physics as well as their potential application in catalytic transformations, gas-separation processes, water purification and so on. Here, we critically review MPs with respect to the sustainability aspects of their synthesis as well as their applications that have sustainable character. Some MPs have been synthesized from monomers derived from biomass resources, but there is certainly a large potential for further *** are also opportunities to improve the sustainability of MP synthesis in terms of the use of solvents, catalysts, and related aspects. The applications of MPs in processes related to sustainability depend upon multiple properties. A rich and flexible chemistry is important to applications as catalysts for, among other useful reactions, the photoreduction of CO_2 and selective oxidation. The(ultra)micropore volume of MPs are crucial in gas-separation applications such as CO_2 capture, and the chemisorption of CO_2 on MP-tethered alkylamines could offer a means to remove that gas from dilute mixtures. When it comes to the storage of H_2 and CH_4 in MPs for onboard use in fuel cell or biogas cars, volumetric capacity is paramount, meaning that the density of the MPs must be considered. Finally, for use in separation and purifications from liquid mixtures(aqueous or hydrocarbon-based), crosslinked MPs are more limited than the solution-processable MPs that can be more easily processed into films and membranes.

关键词： microporous polymers biomass sustainability CO2 capture catalysis H2 storage CH4 storage separation purification

Nanophotonics of higher-plant photosynthetic membranes

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Light(Science & Applications) 2019年第1期8卷 1128-1140页

作者： A.Capretti A.K.Ringsmuth J.Fvan Velzen A.Rosnik R.Croce T.Gregorkiewicz Institute of Physics University of AmsterdamAmsterdamNetherlands Dep.Physics and Astronomy VU University AmsterdamAmsterdamNetherlands College of Chemistry University of CaliforniaBerkeleyCAUSA stockholm Resilience Centre Stockholm UniversityStockholmSweden

The thylakoid membrane inside chloroplasts hosts the light-dependent reactions of *** embedded protein complexes are responsible for light harvesting,excitation energy transfer,charge separation,and *** higher plants,when the illumination conditions vary,the membrane adapts its composition and nanoscale morphology,which is characterized by appressed and non-appressed regions known as grana and stroma lamellae,*** we investigate the nanophotonic regime of light propagation in chloroplasts of higher plants and identify novel mechanisms in the optical response of the thylakoid *** results indicate that the relative contributions of light scattering and absorption to the overall optical response of grana strongly depend on the concentration of the light-harvesting *** the pigment concentrations typically found in chloroplasts,the two mechanisms have comparable strengths,and their relative value can be tuned by variations in the protein composition or in the granal ***,we find that collective modes in ensembles of grana significantly increase light absorption at selected wavelengths,even in the presence of moderate biological *** variations in the granal separation or a large disorder can dismantle this collective *** propose that chloroplasts use this mechanism as a strategy against dangerously high illumination conditions,triggering a transition to low-absorbing *** conclude that the morphological separation of the thylakoid membrane in higher plants supports strong nanophotonic effects,which may be used by chloroplasts to regulate light *** adaptive self-organization capability is of interest as a model for novel bioinspired optical materials for artificial photosynthesis,imaging,and sensing.

关键词： separation collective illumination

Wood-inspired engineering materials

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Science China Materials 2018年第12期61卷 1625-1626页

作者： Lennart Bergstrom Department of Materials and Environmental Chemistry Stockholm UniversityStockholm 10691Sweden

Nature continues to serve as inspiration for the design and fabrication of high-performance materials [1,2].The structural and compositional features responsible for e.g. the high hardness and fracture toughness of nacre,tooth enamel and other biominerals have served as a bench- mark for the structural design of hard and strong materials [3].Wood has been utilized by humankind for millennia for protection,construction,energy and for cultural and religious *** hierarchical and cellular structure of wood and the structure-property rela- tions of the constituents and their assemblies:e.g. cellulose,hemicellulose and lignin,has been the focus of intense research efforts and resulted in advances in the fabrication of wood-based functional and structural high- performance materials [4,5].

关键词： CMF CPF Wood-inspired engineering materials