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Protective and Regenerative Efficacy of a Plant Oil-Based Day and Night Cream: Investigated by a Novel Approach to Reveal the Impact of Blue Light Irradiation on Epidermal Barrier Integrity and Lipid Matrix

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Journal of Cosmetics, Dermatological Sciences and Applications 2024年第3期14卷 227-241页

作者： Dorothee Dähnhardt Stephan Dähnhardt-Pfeiffer Isabel Simon Dana Ditgen Inge Holland Dörte Segger Peter Staib Microscopy Services Dhnhardt gmbh Flintbek Germany Research & Development and Regulatory Affairs Kneipp GmbH Wuerzburg Germany SGS INSTITUT FRESENIUS gmbh Hamburg Germany

In recent years, the harmful effects of blue light (400 - 500 nm) as a component of visible light (400 - 700 nm) have increasingly gained attention of science, industry, and consumers. To date, only a few in vivo test methods for measuring the effects of blue light on the skin have been described. A direct measurement method that can detect the immediate effects of blue light on the epidermal permeability barrier (EPB) is still lacking. In this study, we present a new methodological approach that can be used to investigate both the protective and regenerative effects of cosmetic products on the EPB after blue light irradiation. In a study with 14 female volunteers, it was investigated whether the regular application of an O/W emulsion (day cream) can strengthen and protect the epidermal barrier against damaging blue light radiation of 60 J/cm2 (protective study design) and also whether a disruption of the epidermal barrier caused by blue light radiation is restored faster and better by the regular application of another O/W emulsion (night cream) than in product-untreated skin (regenerative study design). The two O/W emulsions are different in plant oil, active ingredient composition and texture. The seven-day treatment with the day cream initially led to a significant increase in the normalized lipid lamellae length in the intercellular space, whereas the irradiation with blue light after 24 hours led to a significant decrease in the lipid lamellae length in the untreated test area, but not in the area previously treated with the product. Regarding the regenerative study design, a two-day treatment with the night cream was able to restore a blue-light-induced decrease in lipid lamellae length in the intercellular space. In summary, with the study designs presented here, the protective and regenerative effect of two cosmetic products could be demonstrated for the first time on the integrity of the EPB after blue light irradiation and the data showed that the Lipbarv

关键词： Skin Care Blue Light Irradiation Skin Barrier Intercellular Lipid Lamellae Electron Microscopy

Impact of human sequences in variable domains of therapeutic antibodies on the location of CD4 T-cell epitopes

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Cellular & Molecular Immunology 2020年第6期17卷 656-658页

作者： Sylvain Meunier Moustafa Hamze Anette Karle Marie de Bourayne Abdelaziz Gdoura Sebastian Spindeldreher Bernard Maillère CEA-Saclay Institut Frederic JoliotSIMOPROUniversitéParis-Saclay91191 Gif sur YvetteFrance Novartis Pharma AG BaselSwitzerland present address:Integrated Biologix gmbh BaselSwitzerland

The clinical efficacy of therapeutic antibodies is recognized in many indications,explaining their rapid rise in the worldwide drug ***,therapeutic antibodies can be immunogenic by inducing a specific immune response characterized by the production of anti-drug antibodies(ADAs).ADAs can potentially increase the clearance of therapeutic antibodies,decrease their therapeutic effects1 and induce hypersensitivity *** humans are thought to be tolerant to their own proteins,sequences of the therapeutic antibodies have been humanized or human antibodies have been directly generated by technologies using human ***,human(ized)antibodies exhibit highly variable levels of immunogenicity,1,2 illustrating the poor understanding of the role of sequence humanization in mitigating the immunogenicity of therapeutic *** lines of evidence highlight the role of CD4 T lymphocytes during the initiation of an ADA response,3 but few T-cell epitopes of marketed therapeutic antibodies have been described to date.

关键词： therapeutic antibodies clinical

The Expansion and Diversification of Pentatricopeptide Repeat RNA-Editing Factors in Plants

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Molecular Plant 2020年第2期13卷 215-230页

作者： Bernard Gutmann Santana Royan Mareike Schallenberg-Rudinger Henning Lenz Ian R.Castleden Rose McDowell Michael AVacher Julian Tonti-Filippini Charles SBond Volker Knoop Ian D.Small Australian Research Council Centre of Excellence in Plant Energy Biology The University of Western AustraliaCrawleyPerth 6009WAAustralia School of Molecular Sciences The University of Western AustraliaCrawleyPerth 6009WAAustralia IZMB-Institut fur Zellulare und Molekulare Botanik Abteilung Molekulare EvolutionUniversitat BonnKirschallee 153115 BonnGermany present address:EditForce Inc. West zone#429Kyushu University744 MotookaNishi-KuFukuokaJapan present address:IBG-2:Plant Sciences Forschungszentrum Jiilich GmbH52425 JulichGermany present address:Australian eHealth Research Centre Commonwealth Scientific and Industrial Research OrganisationFloreatPerth 6014WAAustralia

The RNA-binding pentatricopeptide repeat(PPR)family comprises hundreds to thousands of genes in most plants,but only a few dozen in algae,indicating massive gene expansions during land plant *** nature and timing of these expansions has not been well defined due to the sparse sequence data available from early-diverging land plant *** this study,we exploit the comprehensive OneKP datasets of over 1000 transcriptomes from diverse plants and algae toward establishing a clear picture of the evolution of this massive gene family,focusing on the proteins typically associated with RNA editing,which show the most spectacular variation in numbers and domain composition across the plant *** characterize over 2250000 PPR motifs in over 400000 *** lycophytes,polypod ferns,and hornworts,nearly 10%of expressed protein-coding genes encode putative PPR editing factors,whereas they are absent from algae and complex-thalloid *** show that rather than a single expansion,most land plant lineages with high numbers of editing factors have continued to generate novel sequence *** identify sequence variations that imply functional differences between PPR proteins in seed plants versus non-seed plants and variations we propose to be linked to seed-plant-specific editing ***,using the sequence variations across the datasets,we develop a structural model of the catalytic DYW domain associated with C-to-U editing and identify a clade of unique DYW variants that are strong candidates as U-to-C RNA-editing factors,given their phylogenetic distribution and sequence characteristics.

关键词： RNA editing RNA-binding protein organelles

Mechanism of cross-level settlements and void accumulation of wide and conventional sleepers in railway ballast

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Railway Engineering Science 2024年第3期32卷 361-383页

作者： Olga Nabochenko Mykola Sysyn Norman Krumnow Szabolcs Fischer Institute of Railway Systems and Public Transport Technical University of DresdenDresdenGermany Rhomberg Sersa Deutschland gmbh BerlinGermany Central Campus Győr Széchenyi István UniversityGyorHungary

The cross-level and twist irregularities are the most dangerous irregularity types that could cause wheel unloading with the risk of derailments and additional maintenance ***,the mechanism of the irregularities initiation and development is *** motivation of the present study was the previous experimental studies on the application of wide sleepers in the ballasted *** long-term track geometry measurements with wide sleepers show an enormous reduction of the vertical longitudinal irregularities compared to the conventional ***,wide sleepers had higher twist and cross-section level *** present paper aims to explain the phenomenon by discrete element method(DEM)modeling the development process of sleeper inhomogeneous support at cross-level depending on the sleeper *** DEM simulations show that the maximal settlement intensity is up to 3.5 times lower for a wide sleeper in comparison with the conventional ***,the cross-level differential settlements are almost the same for both *** particle loading distribution after all loading cycles is concentrated on the smaller area,up to the half sleeper length,with fully unloaded zones under sleeper *** flow limitation under the central part of the sleeper could improve the resilience of wide sleepers to the development of cross-level *** mechanism of initiation of the cross-level irregularity is proposed,which assumes the loss of sleeper support under sleeper *** further growth of inhomogeneous settlements along the sleeper is assumed as a result of the interaction of two processes:ballast flow due to dynamic impact during void closing and on the other side high pressure due to the concentration of the pressure under the middle part of the *** DEM simulation results support the assumption of the mechanism and agree with the experimental studies.

关键词： Wide sleeper Ballasted track Sleeper support inhomogeneity Sleeper foot form Discrete element modeling Void accumulation

Metabolic characterization of selected probiotic consortia during gluten and wheat bread simulated digestion

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Food Science and Human Wellness 2024年

作者： Mirco Vacca Giuseppe Celano Olga Nikoloudaki Bodo Speckmann Francesco Maria Calabrese Marco Gobbetti Maria de Angelis Faculty of Science and Technology， Free University of Bozen Evonik Operations gmbh Department of Soil Plant and Food Sciences， University of Bari Aldo Moro

While exerting their metabolic activities in the gastrointestinal milieu， probiotics impact the host well-being by boosting immunity， treating metabolic disorders， and modulating microbiota and metabolome. Due to the high incidence of gluten-based disorders， the present work aims to deeply explore the metabolism of two selected microbial consortia (MCs) during gluten digestion under simulated gastrointestinal conditions. Featured by high protease and peptidase activity， both MCs accounted for different lactic acid bacteria and Bacillus strains that were combined with two commercial protease enzymes. Gluten substrates were used as purified extracts， white and whole wheat breads. Control samples， instead， relied onto the microbial enzyme lack. Twenty-four hours of simulated digestion were sufficient to completely hydrolyze gluten in one of the two MC-containing experimental sets， and the relative 48 h-digested extract did not alter the cytokine expression in duodenal biopsies from celiac disease (CeD) patients. When digested samples were assayed for antioxidant and phytase activities， microbial enzymes demonstrated to significantly improve both ABTS and DPPH values and to decrease the phytic acid concentration. The inspection of the free amino acid profiles allowed for distinguishing the two MCs， whereas the detection of a heterogeneous panel of volatile organic compounds supported the presence/activity of microbial enzymes without statistically significant differences between MCs. As functional contribution， digested extracts with MCs also proved to reduce the inflammatory cytokine concentrations in cell lines exposed to lipopolysaccharide trigger. Therefore， in line with studies exploring novel adjuvant therapies， the present innovative probiotic consortium featured by high gluten-hydrolyzing metabolism also showed the capability to improve various parameters usually found to be altered in patients affected by gluten-based disorders or CeD.

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The effect of Laves phases and nano-precipitates on the electrochemical corrosion resistance of Mg-Al-Ca alloys under alkaline conditions

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Journal of Magnesium and Alloys 2024年第6期12卷 2447-2461页

作者： Markus Felten Veronika Chaineux Siyuan Zhang Ali Tehranchi Tilmann Hickel Christina Scheu Joshua Spille Marta Lipińska-Chwałek Joachim Mayer Benjamin Berkels Marcus Hans Imke Greving Silja Flenner Sandra Sefa Daniela Zander Chair of Corrosion and Corrosion Protection RWTH Aachen UniversityAachen 52072 Germany Max-Planck-Institut für Eisenforschung gmbh Düsseldorf 40237 Germany Central Facility for Electron Microscopy RWTH Aachen UniversityAachen 52074 Germany Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons Forschungszentrum Jülich GmbHJülich 52428Germany Mathematical Image and Signal Processing Aachen Institute for Advanced Study in Computational Engineering ScienceRWTH Aachen UniversityAachen 52062 Germany Materials Chemistry RWTH Aachen UniversityAachen 52074 Germany Institute of Materials Physics Helmholtz-Zentrum HereonGeesthacht 21502 Germany

The electrochemical corrosion mechanisms of Mg alloys were extensively studied in previous investigations of different chemical com-positions,modified surface states and various electrolyte ***,recent research focused on the active state of Mg dissolution,leading to unresolved effects of secondary phases adjacent to a stableα-solid solution passive *** present study investigates the fundamental electrochemical corrosion mechanisms of three different Laves phases with varying phase morphologies and phase fractions in the passive state of Mg-Al-Ca *** microstructure was characterized by(transmission-)electron microscopy and synchrotron-based transmission X-ray *** electrochemical corrosion resistance was determined with a standard three-electrode setup and advanced in-situ flow cell measurements.A new electrochemical activity sequence(C15>C36>α-Mg>C14)was obtained,as a result of a stable passive layer formation on theα-solid ***,nm-scale Mg-rich precipitates were identified within the Laves phases,which tend to inhibit the corrosion kinetics.

关键词： Laves phase STEM Magnesium Corrosion Passive layer

Targeting α-synuclein by PD03 AFFITOPE■ and Anle 138b rescues neurodegenerative pathology in a model of multiple system atrophy:clinical relevance

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Translational Neurodegeneration 2020年第3期9卷 484-497页

作者： Miguel Lemos Serena Venezia Violetta Refolo Antonio Heras-Gavin Sabine Schmidhuber Armin Giese Andrei Leonov Sergey Ryazanov Christian Griesinger Gergana Galabova Guenther Safer Gregor Karl Wenning Nadia Stefanova Division of Neurobiology Department of NeurologyInnsbruck Medical University6020 InnsbruckAustria AFFIRIS AG ViennaAustria Center for Neuropathology and Prion Research Ludwig-Maximilians-UniversityMunichGermany Max Planck Institute for Biophysical Chemistry GottingenGermany present address:origenis gmbh MunichGermany

Background:Misfolded oligomeric α-synuclein plays a pivotal role in the pathogenesis of a-synucleinopathies including Parkinson's disease and multiple system atrophy,and its detection parallels activation of microglia and a loss of neurons in the substantia nigra pars *** we aimed to analyze the therapeutic efficacy of PD03,a new AFFITOPE■ immunotherapy approach,either alone or in combination with Anle138b,in a PLP-α-syn mouse ***:The PLP-α-syn mice were treated with PD03 immunotherapy,Anle138b,or a combination of *** months after study initiation,the mice underwent behavioral testing and were sacrificed for neuropathological *** treatment groups were compared to the vehicle group with regard to motor performance,nigral neuronal loss,microglial activation and α-synuclein ***:The PLP-α-syn mice receiving the PD03 or Anle138b single therapy showed improvement of gait deficits and preservation of nigral dopaminergic neurons associated with the reduced α-synuclein oligomer levels and decreased microglial *** combined therapy with Anle138b and PD03 resulted in lower lgG binding in the brain as compared to the single immunotherapy with ***:PD03 and Anle138b can selectively target oligomeric α-synuclein,resulting in attenuation of neurodegeneration in the PLP-α-syn *** approaches are potential therapies that should be developed further for disease modification in α-synucleinopathies.

关键词： α-Synuclein Immunotherapy Oligomer modulation Target engagement Substantia nigra Microglia

Performance of two complementary machine-learned potentials in modelling chemically complex systems

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npj Computational Materials 2023年第1期9卷 1008-1022页

作者： Konstantin Gubaev Viktor Zaverkin Prashanth Srinivasan Andrew Ian Duff Johannes Kästner Blazej Grabowski Institute for Materials Science University of StuttgartPfaffenwaldring 5570569 StuttgartGermany Institute for Theoretical Chemistry University of StuttgartPfaffenwaldring 5570569 StuttgartGermany Scientific Computing Department STFC Daresbury LaboratoryWarrington WA44ADUK present address:NEC Laboratories Europe gmbh Kurfürsten-Anlage 3669115 HeidelbergGermany

Chemically complex multicomponent alloys possess exceptional properties derived from an inexhaustible compositional *** complexity however makes interatomic potential development *** explore two complementary machine-learned potentials—the moment tensor potential(MTP)and the Gaussian moment neural network(GM-NN)—in simultaneously describing configurational and vibrational degrees of freedom in the Ta-V-Cr-W alloy *** models are equally accurate with excellent performance evaluated against *** achieve root-mean-square-errors(RMSEs)in energies of less than a few meV/atom across 0 K ordered and high-temperature disordered configurations included in the *** for compositions not in training,relative energy RMSEs at high temperatures are within a few meV/***-temperature molecular dynamics forces have similarly small RMSEs of about 0.15 eV/Åfor the disordered quaternary included in,and ternaries not part of *** achieve faster convergence with training size;GM-NNs are faster in *** learning is partially beneficial and should be complemented with conventional human-based training set generation.

关键词： alloy faster complex

Theplant cytosolic m^(6)A RNA methylome stabilizes photosynthesis in the cold

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Plant Communications 2023年第6期4卷 70-84页

作者： Alexandre Magno Vicente Nikolay Manavski Paul Torben Rohn Lisa-Marie Schmid Antoni Garcia-Molina Dario Leister Charlotte Seydel Leo Bellin Torsten Möhlmann Gregor Ammann Stefanie Kaiser Jörg Meurer Plant Molecular Biology Faculty of BiologyLudwig-Maximilians-University MunichGroßhaderner Street 2-482152 Planegg-MartinsriedGermany Plant Development Faculty of BiologyLudwig-Maximilians-University MunichGroßhaderner Street 2-482152 Planegg-MartinsriedGermany Plant Physiology Faculty of BiologyUniversity of KaiserslauternErwin-Schröodinger-Street767663 KaiserslauternGermany Pharmaceutical Chemistry Goethe University FrankfurtMax-von-Laue-Str.960438 Frankfurt am MainGermany present address:Loewe Biochemica gmbh Möuhlweg 2a82054 SauerlachGermany present address:Center for Research in Agricultural Genomics 08193

The sessile lifestyle of plants requires an immediate response to environmental stressors that affect photosynthesis,growth,and crop ***,we showed that three abiotic perturbations—heat,cold,and high light—triggered considerable changes in the expression signatures of 42 epitranscriptomic factors(writers,erasers,and readers)with putative chloroplast-associated functions that formed clusters of commonly expressed genes in *** expression changes under all conditions were reversible upon deacclimation,identifying epitranscriptomic players as modulators in acclimation *** dysfunctions,particularly those induced by the oxidative stress-inducing norflurazon in a largely GENOME UNCOUPLED-independent manner,triggered retrograde signals to remodel chloroplastassociated epitranscriptomic expression patterns.N6-methyladenosine(m^(6)A)is known as the most prevalent RNA modification and impacts numerous developmental and physiological functions in living *** cold treatment,expression of components of the primary nuclear m^(6)A methyltransferase complex was upregulated,accompanied by a significant increase in cellular m^(6)A mRNA *** the cold,the presence of FIP37,a core component of the writer complex,played an important role in positive regulation of thylakoid structure,photosynthetic functions,and accumulation of photosystemⅠ,the Cytb6f complex,cyclic electron transport proteins,and Curvature Thylakoid1 but not that of photosystemⅡcomponents and the chloroplast ATP *** of FIP37 affected abundance,polysomal loading,and translation of cytosolic transcripts related to photosynthesis in the cold,suggesting m^(6)Adependent translational regulation of chloroplast *** summary,we identified multifaceted roles of the cellular m^(6)A RNA methylome in coping with cold;these were predominantly associated with chloroplasts and served to stabilize photosynthesis.

关键词： m^(6)A RNA methylation cold acclimation stress response Arabidopsis thaliana photosynthesis chloroplast