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Interleukin-1 beta induces the expression and production of stem cell factor by epithelial cells： crucial involvement of the PI-3K/mTOR pathway and HIf-1 transcription complex

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Cellular & Molecular Immunology 2016年第1期13卷 47-56页

作者： Rafal W Wyszynski bernhard f gibbs Luca Varani Daniela Iannotta Vadim V Sumbayev School of Pharmacy University of Kent Kent UK Institute for Research in Biomedicine Bellinzona Switzerland These authors are Contributed equally to this study

Potential crosslinks between inflammation and leukaemia have been discussed for some time, but experimental evidence to support this dogma is scarce. In particular, it is important to understand the mechanisms responsible for potential upregulation of proto-oncogenic growth factor expressions by inflammatory mediators. Here, we investigated the ability of the highly inflammatory cytokine interleukin-1 beta （IL-1β） to induce the production of stem cell factor （SCf）, which is a major hematopoietic growth factor that controls the progression of acute myeloid leukaemia upon malignant transformation of haematopoietic myeloid cells. We found that human IL-1β induced the expression/secretion of SCf in MCf-7 human epithelial breast cancer cells and that this process depended on the hypoxia-inducible factor 1 （HIf-1） transcription complex. We also demonstrated a crucial role of the phosphatidylinositol-3 kinase （PI-3K）/mammalian target of rapamycin （mTOR） pathway in IL-1β-induced HIf-1α accumulation in MCf-7 cells. Importantly, mTOR was also found to play a role in IL-1β-induced SCf production. furthermore, a tendency for a positive correlation of IL-1β and SCf levels in the plasma of healthy human donors was observed. Altogether, our results demonstrate that IL-1β, which normally bridges innate and adaptive immunity, induces the production of the major haematopoietic/proleukaemic growth factor SCf through the PI-3K/mTOR pathway and the HIf-1 transcription complex. These findings strongly suoDort a cross-talk between inflammation and acute mveloid leukaemia.

关键词： Inflammation Stem cell factor Leukaemia Hypoxia

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Biochemical mechanisms implemented by human acute myeloid leukemia cells to suppress host immune surveillance

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Cellular & Molecular Immunology 2018年第11期15卷 989-991页

作者： Inna M.Yasinska Isabel Gonçalves Silva Svetlana Sakhnevych bernhard f.gibbs Ulrike Raap Elizaveta fasler-Kan Vadim V.Sumbayev Medway School of Pharmacy Universities of Kent and GreenwichChatham MaritimeUK Department of Dermatology and Allergy University of OldenburgOldenburgGermany Department of Pediatric Surgery and Department of Biomedical Research Children’s HospitalInselspitalUniversity of BernBernSwitzerland Department of Biomedicine University Hospital Basel and University of Basel BaselSwitzerland

Acute myeloid leukaemia(AML)is a blood/bone marrow cancer originating from myeloid cell precusors capable of *** cells implement biochemical mechanisms which allow them not only to survive,but also to successfully escape immune *** this work,we discuss crucial molecular mechanisms used by human AML cells in order to evade immune attack.

关键词： Acute myeloid leukaemia Immune surveillance Tim-3 galectin-9

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Cortisol facilitates the immune escape of human acute myeloid leukemia cells by inducing latrophilin 1 expression

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Cellular & Molecular Immunology 2018年第11期15卷 994-997页

作者： Svetlana S.Sakhnevych Inna M.Yasinska Alison M.Bratt Ouafa Benlaouer Isabel Gonçalves Silva Rohanah Hussain Giuliano Siligardi Walter fiedler Jasmin Wellbrock bernhard f.gibbs Yuri A.Ushkaryov Vadim V.Sumbayev Medway School of Pharmacy Universities of Kent and GreenwichChatham MaritimeUK Beamline B23 Diamond Light SourceDidcotUK Department of Oncology Hematology and Bone Marrow Transplantation with Section PneumologyHubertus Wald University Cancer CenterUniversity Medical Center Hamburg-EppendorfHamburgGermany Department of Medicine Dermatology and AllergologyUniversity of OldenburgOldenburgGermany

The progression of acute myeloid leukemia(AML)—the most severe blood/bone marrow cancer—is determined by the ability of malignant cells to escape host immune ***,the systemic regulatory mechanisms underlying this phenomenon remain largely *** this study,we discovered a fundamental systemic biochemical strategy that allows AML cells to employ physiological systems within the body to survive and escape immune *** found that AML cells use a crucial human adrenal cortex hormone(cortisol)to induce the expression of neuronal receptor latrophilin 1(LPHN1),which facilitates *** receptor interacts with the blood plasma protein fibronectin leucine rich transmembrane protein 3(fLRT3)to cause secretion of the immune suppressor galectin-9,which impairs the anticancer activities of cytotoxic lymphoid cells.

关键词： acute myeloid cortex

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Event segmentation in ADHD:neglect of social information and deviant theta activity point to a mechanism underlying ADHD

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General Psychiatry 2024年第3期37卷 431-439页

作者： Astrid Prochnow Xianzhen Zhou foroogh Ghorbani Veit Roessner bernhard Hommel Christian Beste Cognitive Neurophysiology Department of Child and Adolescent PsychiatryFaculty of MedicineTU DresdenDresdenGermany faculty of Psychology Shandong Normal UniversityJinanShandongChina

Background Attention-deficit/hyperactivity disorder(ADHD)is one of the most frequently diagnosed psychiatric conditions in children and *** the symptoms appear to be well described,no coherent conceptual mechanistic framework integrates their occurrence and variance and the associated problems that people with ADHD *** The current study proposes that altered event segmentation processes provide a novel mechanistic framework for understanding deficits in *** Adolescents with ADHD and neurotypically developing(NT)peers watched a short movie and were then asked to indicate the boundaries between meaningful segments of the *** recorded electroencephalography(EEG)data were analysed for differences in frequency band activity and effective connectivity between brain *** Compared with their NT peers,the ADHD group showed less dependence of their segmentation behaviour on social information,indicating that they did not consider social information to the same extent as their unaffected *** divergence was accompanied by differences in EEG theta band activity and a different effective connectivity network architecture at the source ***,NT adolescents primarily showed error signalling in and between the left and right fusiform gyri related to social information processing,which was not the case in the ADHD *** the ADHD group,the inferior frontal cortex associated with attentional sampling served as a hub instead,indicating problems in the deployment of attentional *** This study shows that adolescents with ADHD perceive events differently from their NT peers,in association with a different brain network architecture that reflects less adaptation to the situation and problems in attentional sampling of environmental *** results call for a novel conceptual view of ADHD,based on event segmentation theory.

关键词： instead meaningful primarily

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Demonstrating grating-based phase-contrast imaging of laser-driven shock waves

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Matter and Radiation at Extremes 2024年第4期9卷 90-97页

作者： Leonard Wegert Stephan Schreiner Constantin Rauch Bruno Albertazzi Paulina Bleuel Eric frojdh Michel Koenig Veronika Ludwig Artem SMartynenko Pascal Meyer Aldo Mozzanica Michael Müller Paul Neumayer Markus Schneider Angelos Triantafyllidis bernhard Zielbauer Gisela Anton Thilo Michel Stefan funk Plasma Physics Department GSI Helmholtzzentrum fur SchwerionenforschungPlanckstraBe 164291 DarmstadtGermany Erlangen Centre for Astroparticle Physics(ECAP) Friedrich-Alexander-Universität Erlangen-NurnbergNikolaus-Fiebiger-StraBe 291058 ErlangenGermany LULI-CNRS CEASorbonne UniversitésEcole PolytechniqueInstitut Polytechnique de ParisF-91120 Palaiseau CedexFrance Paul Scherrer Institut(Psi) Forschungsstrasse 1115232VilligenSwitzerland Karlsruhe Institute of Technology Institute of Microstructure TechnologyHermann-von-Helmholtz-Platz 176344 Eggenstein-LeopoldshafenGermany

Single-shot X-ray phase-contrast imaging is used to take high-resolution images of laser-driven strong shock *** a two-grating Talbot interferometer,we successfully acquire standard absorption,differential phase-contrast,and dark-field images of the shocked *** agreement is demonstrated between experimental data and the results of two-dimensional radiation hydrodynamics simulations of the laser-plasma *** main sources of image noise are identified through a thorough assessment of the interferometer’s *** acquired images demonstrate that grating-based phase-contrast imaging is a powerful diagnostic tool for high-energy-density *** addition,we make a novel attempt at using the dark-field image as a signal modality of Talbot interferometry to identify the microstructure of a foam target.

关键词： interaction. shock phase

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Quantifying Kinematic Tremor in an NGLY1-Deficient Individual: A Case Study

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Case Reports in Clinical Medicine 2024年第1期13卷 25-36页

作者： Brock futrell Christopher Alexander Malaya Dacia Martinez Diaz Christian Alfaro Hannah Elizabeth Gustafson Subhalakshmi Chandrasekaran Rhea Mohan Phatak bernhard Suter Charles Shannon Layne Department of Health and Human Performance University of Houston Houston USA Center for Neuromotor and Biomechanics Research University of Houston Houston USA Department of Computer Science and Engineering Texas A&M University College Station USA Blue Bird Circle Rett Center Texas Children’s Hospital Houston USA Baylor College of Medicine Houston USA Center for NeuroEngineering and Cognitive Science University of Houston Houston USA

NGLY1 Deficiency is an autosomal recessive congenital disorder that has been identified in less than 100 individuals. Most individuals with NGLY1 Deficiency display hyperkinetic movement disorders, including choreiform, athetoid, dystonic myoclonic, dyskinetic, and dysmetric movements. Developing a consistent and concise consensus on the classification and evaluation of tremors is essential to forward the research and treatment of tremors. It has also been reported that some individuals with NGLY1 Deficiency demonstrate tremor, but such tremor has never been formally investigated. The primary objective of this study is to determine if an individual with NGLY1 Deficiency demonstrates an identifiable tremor during a series of arm movements and, if so, describe the frequency and power characteristics of that tremor. Arm movement kinematics were obtained using a 16-camera Vicon system, and time series trajectory waveforms for three planes of a marker placed on the hand were developed. Custom MATLAB scripts were utilized to compute fast fourier Transformations of the data within the identified waveform segments. A mean frequency of 2.30 Hz (SD = 1.05) with a mean power of 5.02 |P1(f)| (SD = 4.63) suggests that our participant’s kinematic data did display a persistent tremor in both hands across all tasks and movement planes. Analyses of the reaching hand and the non-reaching hand suggest the participant displayed an action tremor in both postural and intention (kinetic) tremors. future directions should include assessing additional individuals with NGLY1 Deficiency to determine if the tremor is a distinguishable disorder behavior. Additionally, evaluating other anatomical sites, such as the elbow, head, and lower limbs, would provide further insights into the characteristics of this tremor.

关键词： Tremor NGLY fast fourier Transformation Reaching Hyperkinetic Movement

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Effect of excitation wavelength(blue vs near UV)and dopant concentrations on afterglow and fast decay of persistent phosphor SrAl_(2)O_(4):Eu^(2+),Dy^(3+)

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Journal of Rare Earths 2022年第7期40卷 1022-1028页

作者： bernhard Walfort Nando Gartmann Jafar Afshani Arnulf Rosspeintner Hans Hagemann LumiNova AG SwitzerlandSpeicherstrasse 60aCH-9053TeufenSwitzerland Dépt.de Chimie Physique Universitéde Genève30Quai E.AnsermetCH 1211Geneva 4Switzerland

The persistent phosphor SrAl_(2)O_(4):Eu^(2+),Dy^(3+)is the subject of numerous *** often neglected aspect is that in this phosphor,as well as in Sr_(4)Al_(14)O_(25):Eu^(2+),Dy^(3+),there are two different Sr^(2)+sites which can be occupied by the dopant Eu^(2+)ions,We first introduce a general scheme of possible energy transfers in these persistent phosphor materials including explicitly both europium ions,This scheme is used as a generic starting point to study experimentally specific *** illustrate this application with the study of the effect of excitation wavelength(444 and 382 nm)on the afterglow of differently doped SrAl_(2)O_(4):Eu^(2+),Dy^(3+)samples,as well as on the emission decay *** the same excitation intensity under 444 nm excitation,the resulting afterglow intensity is stronger than under near UV *** 382 nm,Eu^(2+)ions on both Sr^(2)+s ites in SrAl_(2)O_(4)are excited,but at room temperature the blue emission is quenched,leading to a loss of *** observed effects can further be associated with the ratio of Eu^(2+)ions and trap states which are modulated by the concentrations of Eu^(2+)and Dy^(3+)in SrAl_(2)O_(4),as well as by temperature,Increasing the nominal Dy^(3+)content from 0.1 mol%to 0.5 mol%with respect to Sr results in the doubling of the integrated afterglow intensity and confirms thus that Dy^(3+)ions are indeed involved in the trapping process,The concentration of trap states is much lower than the concentration of Eu^(2+)ions,as even with low excitation densities,a plateau of integrated afterglow intensity(corresponding to the total number of accessible traps)is *** postulate that an important fraction of excited Eu^(2+)ions can potentially transfer their energy to trap *** that all traps are filled or in a dynamical filling-depletion process under illumination(with thermal and/or optical depletion processes),for the remaining Eu^(2+)a"normal"steady-state emission is observed

关键词： Persistent phosphor Strontium aluminate Europium forster energy transfer Rare earths

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Multimodal 4-arylchromene derivatives with microtubule-destabilizing,anti-angiogenic,and MYB-inhibitory activities

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Cancer Drug Resistance 2023年第1期6卷 59-77页

作者： Leonhard H.f.Kohler Sebastian Reich Maria Yusenko Karl-Heinz Klempnauer Gerrit Begemann Rainer Schobert bernhard Biersack Organic Chemistry Laboratory University of BayreuthBayreuth 95440Germany Institute for Biochemistry Westfalische-Wilhelms-UniversitatMunster 48149Germany Developmental Biology University of BayreuthBayreuth 95440Germany

Aim:Efficient and readily available anticancer drugs are sought as treatment *** this reason,chromene derivatives were prepared using the one-pot reaction and tested for their anticancer and anti-angiogenic ***:2-Amino-3-cyano-4-(aryl)-7-methoxy-4H-chromene compounds(2A-R)were repurposed or newly synthesized via a three-component reaction of 3-methoxyphenol,various aryl aldehydes,and *** performed assays to study the inhibition of tumor cell growth[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromid(MTT)assay],effects on microtubules(immunofluorescence),cell cycle(flow-activated cell sorting analysis),angiogenesis(zebrafish model),and MYB activity(luciferase reporter assay).fluorescence microscopy was applied for localization studies via copper-catalyzed azide-alkyne click reaction of an alkyne-tagged drug ***:Compounds 2A-C and 2f exhibited robust antiproliferative activities against several human cancer cell lines(50%inhibitory concentrations in the low nanomolar range)and showed potent MYB *** alkyne derivative 3 was localized in the cytoplasm after only 10 min of *** microtubule disruption and G2/M cell-cycle arrest were observed,where compound 2f stood out as a promising microtubule-disrupting *** study of anti-angiogenic properties showed that 2A was the only candidate with a high potential to inhibit blood vessel formation in ***:The close interplay of various mechanisms,including cell-cycle arrest,MYB inhibition,and anti-angiogenic activity,led to identifying promising multimodal anticancer drug candidates.

关键词： Chromene pyran anticancer drugs microtubule angiogenesis MYB inhibition

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“Wood-nacre”:Development of a Bio-inspired Wood-Based Composite for Beam and 3D-Surface Elements with Improved failure Mechanisms

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Journal of Bionic Engineering 2023年第4期20卷 1701-1711页

作者： Ulrich Müller Peter Halbauer Alexander Stadlmann Maximilian Grabner Hajir Al-musawi bernhard Ungerer Maximilian Pramreiter Department of Material Science and Process Engineering Institute of Wood Technology and Renewable MaterialsUniversity of Natural Resources and Life SciencesKonrad-Lorenz-Straße 243430Tulln an der DonauAustria Hycobility Engineering&Technologies GmbH Stadiongasse 6-8/Top281010ViennaAustria

following the natural structure of the nacre,the material studied consists of a multitude of hexagonal tiles that are glued together in an offset manner with a ductile *** so-called“wood nacre”consists of macroscopic tiles of birch wood veneer with a thickness of 0.8 mm and a size of 20 or 10 mm in diameter in order to mimic the aragonite tiles and the ductile PUR-adhesive corresponds to the layers of collagen in between.E-modulus(MOE),bending strength(MOR)and impact bending strength of the samples were determined and compared with reference samples of birch laminated *** hierarchical layered structure of the tiles does not cause any relevant loss in *** nacre,“wood nacre”also shows tough fracture behaviour and a high homogenization ***,strain hardening and high fracture toughness of the natural model could not be fully *** reason for this is the insufficient ratio between the strength and stiffness of the veneer layers and the *** adjusting the size of the tiles,increasing the strength and surface roughness of the veneers,*** densification,and using more ductile adhesives that can be applied in smaller layer thicknesses,it should be possible to better reproduce the natural ratios of nacre and thus achieve a significant improvement in the material properties of“wood nacre”.In addition to the mechanical properties,the high potential of the new material lies in the possibility of producing 3D shell-shaped elements for lightweight wood hybrid construction.

关键词： Bio-inspired Damage tolerance failure behaviour Hierarchical structure Nacre Work of fracture

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Proteome-Based Clustering Approaches Reveal Phylogenetic Insights into Amphistegina

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Journal of Earth Science 2022年第6期33卷 1469-1479页

作者： Marleen Stuhr bernhard Blank-Landeshammer Achim Meyer Vera Baumeister Jörg Rahnenführer Albert Sickmann Hildegard Westphal Leibniz Centre for Tropical Marine Research(ZMT) BremenGermany Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V. DortmundGermany Austrian Competence Center for feed and food Quality Safety and InnovationWelsAustria Chrestos Concept GmbH&Co KG EssenGermany Department of Statistics TU Dortmund UniversityDortmundGermany Medizinisches Proteom-Center(MPC) Ruhr-Universität BochumBochumGermany Department of Chemistry University of AberdeenOld AberdeenScotlandUK Department of Geosciences Bremen UniversityBremenGermany King Abdullah University of Science and Technology(KAUST) ThuwalSaudi Arabia

foraminifera are highly diverse and have a long evolutionary *** key bioindicators,their phylogenetic schemes are of great importance for paleogeographic applications,but may be hard to recognize *** phylogenetic relationships within the prominent genus Amphistegina are still *** studies on Amphistegina have so far only focused on genetic diversity within single species and suggested a cryptic diversity that demands for further *** molecular sequencing-based approaches,different mass spectrometry-based proteomics approaches are increasingly used to give insights into the relationship between samples and organisms,especially as these do not require reference *** better understand the relationship of amphisteginids and test different proteomics-based approaches we applied de novo peptide sequencing and similarity clustering to several populations of Amphistegina lobifera,*** and *** also analyzed the dominant photosymbiont community to study their influence on holobiont *** analyses indicate that especially de novo peptide sequencing allows to reconstruct the relationship among foraminiferal holobionts,although the detected separation of *** from *** and *** may be partly influenced by their different photosymbiont *** resulting dendrograms reflect the separation in two lineages previously suggested and provide a basis for future studies.

关键词： large benthic foraminifera de novo peptide sequencing tandem mass spectra clustering LC-MS/MS runs proteomics symbiont diversity phylogeography fragilariales

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