Podcasts about Hoechst

In this podcast, Professor Ian Wilson, a globally recognised and leading expert in drug metabolism, with over 500 publications in the field, takes us on an engaging journey exploring the link between carboxylic acid containing drugs and their involvement in DILI. A special focus will be given to Ian's latest paper: ‘Minimizing the DILI potential of carboxylic acid-containing drugs: a perspective'.The episode explores the following:Are acyl glucuronides shouldering too much of the blame?Where else should we be looking?What are the possible risk mitigation strategies to reduce DILI with these chemotypes?Speaker:Ian Wilson – Professor, Department of Metabolism, Digestion and Reproduction at Imperial CollegeIan Wilson trained as a biochemist at the University of Manchester Institute of Science and Technology UMIST) following this with a PhD in the Chemistry Dept. at Keele University on the gas chromatographic analysis of ecdysteroids (insect moulting hormones). Following a short period of postdoctoral research on HPLC-based methods for the analysis of penicillamine at University College in London he joined Pharma were he the embarked on a career in drug metabolism and bioanalysis is the pharmaceutical industry spanning over 30 years (beginning in 1979 at Hoechst, the ICI, Zeneca and AstraZeneca). On leaving AstraZeneca he joined Imperial College (London) in 2012 where he is currently a Visiting Professor of Drug Metabolism and Molecular Toxicology. More recently he has also been appointed as a visiting Prof at Liverpool University. As a biochemist turned analytical chemist, he tries to use advanced analytical methods, including those based on UHPLC and ion mobility separations to better characterize and understand biological systems. Currently these efforts are focused on high resolution, high throughput methods that can be applied to problems in metabolic phenotyping (metabonomics/metabolomics), drug metabolism/biochemical toxicology, systems biology and the microbiome. He is the author, or co-author, of over 600 papers, reviews or book chapters, and has received awards in separation and analytical science from the Royal Society of Chemistry and the Chromatographic Society amongst others.  Stay tuned for more podcasts in our Pharmaron DMPK Insights Series!

Tanja Valérien spricht mit der PR-Expertin, Autorin und Karl Lagerfeld-Kennerin MARIETTA ANDREAE in ihrem Zuhause in Hamburg über ihre langjährige Tätigkeit bei CHANEL als PR-Direktor für Deutschland und Österreich verantwortlich für deren gesamte Produktlinien ... ihre Zusammenarbeit und Freundschaft mit KARL LAGERFELD, die gemeinsamen Projekte und Erlebnisse, seine Persönlichkeit, seine Liebenswürdigkeit, Großzügigkeit und über ihr Buch “Mein Geheimrat Lagerfeld", welches 2023 erschienen ist... ihre Erfahrungen im Klosterinternat Wald und später als Au Pair-Mädchen in London…den Handkuss…Zurückhaltung…Gesellschaft, Bälle, Benimm…das verwöhnt sein vom Leben und erwachsen werden…die Lehrjahre bei Hoechst in Australien, das darauffolgende Wirken und Tun bei der Kosmetikfirma Marbert in Düsseldorf und die Fügung zu Chanel zu wechseln….Expertise, Wandlung, Schicksal, Liebe, Musik, Familienzusammenhalt, Tod und Vergänglichkeit.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.06.548042v1?rss=1 Authors: Fu, H., Li, J., Zhang, C., Du, P., Gao, G., Ge, Q., Guan, X., Cui, D. Abstract: Senile plaque blue autofluorescence in the Alzheimers disease (AD) was discovered around 40 years ago, however, its impact on AD pathology is not fully examined. We analyzed senile plaques with immunohistochemistry and fluorescence imaging on AD brain pathological sections and also the A{beta} aggregation process in vitro in test tubes. In DAPI or Hoechst staining experiments, the data showed that the nuclear blue fluorescence could only be correctly assigned after subtracting the blue autofluorescence background. The plaque cores have very strong blue autofluorescence which is roughly 2.09 times of average DAPI nuclear staining and roughly 1.78 times of average Hoechst nuclear staining. The composite flower-like structures formed by Cathepsin D lysosomal staining wrapping dense core blue fluorescence should not be considered as central-nucleated neurons filled with defective lysosomes since there was no nuclear staining in the plaque core when the blue autofluorescence was subtracted. Furthermore, the dense cores were shown to be completely lack of nuclear signals by PI staining. The A{beta} aggregation assay indicated that both A{beta} self-oligomers and A{beta}/Hemoglobin (Hb) heterocomplexes had significant blue autofluorescence. However, the blue autofluorescence intensity was not always proportional to the intensity of A{beta} immunostaining. The majority of aggregates in the A{beta}/Hb incubations were sensitive to Proteinase K (PK) digestion while the rest were PK resistant. The blue autofluorescence of A{beta} aggregates not only labels senile plaques but also illustrates red blood cell aggregation, hemolysis, CAA, vascular amyloid plaques, vascular adhesion and microaneurysm. In summary, we conclude that A{beta}-aggregation-generated blue autofluorescence is an excellent amyloid pathology marker in the senile plaques, blood and vascular pathologies in the Alzheimers disease. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Dr. Christian Müller möchte etwas bewirken und im großen Maßstab nachhaltige Energieinnovationen ermöglichen, um Energiekosten zu senken, die Systemleistung zu erhöhen und Treibhausgasemissionen zu reduzieren. Er ist CEO von EIT InnoEnergy in der DACH-Region und Mitglied des Executive Board der europäischen Holding KIC InnoEnergy SE. Er studierte Chemieingenieurwesen an der Universität Karlsruhe und der University of California, Berkeley und erwarb 1996 einen Doktortitel in technischer Thermodynamik. Bevor er zu Europas führendem Cleantech-Investor EIT InnoEnergy kam, war er fast 25 Jahre in der Technologieentwicklung globaler Konzerne tätig. Mit der Übernahme der Corporate Technology Sparte von Hoechst kam er im Jahre 2000 zu Siemens, wo er in führenden Managementpositionen im Bereich der Kommerzialisierung neuer Technologien und Dienstleistungen sowie im Marktpositionierung und Geschäftsentwicklung aktiv war. Das Unternehmen EIT InnoEnergy hat seit seinem Start 560 Millionen Euro in mehr als 480 nachhaltige Energieinnovationen investiert, die bis 2026 einen Umsatz von 16 Milliarden Euro erwirtschaften sollen. 90 % der Start-ups arbeiten bereits mit globalen Marken wie ABB, BMW, EDF, Engie, Tata Steel und Vattenfall zusammen. Die EIT InnoEnergy Master School hat Studierende aus fast 100 Ländern angezogen. Inzwischen hat die Master School 1 200 Absolvent:innen und 1500 eingeschriebene Student:innen.

Dr Altman is a well-known Australian authority on clinical trials and regulatory affairs with more than 40 years of experience in designing, managing and reporting of clinical trials and in working with the Australian Therapeutic Goods Administration in gaining new drug approvals. He has worked in senior managerial positions for several multinational companies including Merrell-Dow, Hoechst, Roussel and GD Searle. He established Australia's first contract research organisations (CROs), where he served as a Senior Industry Consultant for more than half of the pharmaceutical companies present in Australia. His career has seen him involved in more than one hundred clinical trials (Phase I through IV). He has been personally responsible for the market approval of numerous new drugs since joining the pharmaceutical industry in 1974. A graduate of Sydney University with an Honours degree in Pharmacy, Master of Science and Doctor of Philosophy (pharmacology and pharmaceutical chemistry) degrees, he co-founded and is a Life Member of the largest professional body of pharmaceutical industry scientists involved in clinical research and regulatory affairs (Association of Regulatory and Clinical Scientists to the Australian Pharmaceutical Industry Ltd. - ARCS). ARCS presently has more than 2000 members. More recently Dr. Altman has presented to the Cross Party Covid Inquiry held in Brisbane and has provided expert reports in relation to both the Australian and NZ Judicial Review and High Court cases in relation to the Covid vaccines

Barbara Liebermeister ist Managementberaterin, Buchautorin und Rednerin. Sie begann ihre berufliche Karriere im Marketing internationaler Konzerne (u. a. Christian Dior, L'Oréal und Hoechst). Ihre Schwerpunktthemen sind Leadership, (Selbst-)Führung und Beziehungsmanagement im digitalen Zeitalter. Sie berät und coacht vorrangig Führungskräfte und angehende Führungskräfte von Start-up-Unternehmen bis hin zum Dax-Konzern – jeweils abgestimmt auf deren individuellen Businessalltag und Bedarf. Barbara Liebermeister ist Gründerin und Leiterin des Instituts für Führungskultur im digitalen Zeitalter (IFIDZ), Frankfurt am Main. Das Institut erforscht und fördert die Management- und Führungskultur im Zeichen der Digitalisierung und entwickelt Methoden, mit denen die Digital- und die Führungsreife der Führungskräfte nachhaltig gesteigert werden können. Sie ist Dozentin an folgenden Hochschulen: RWTH Aachen, Hochschule Kempten und an der Bucerius Law School in Hamburg. Gleichzeitig ist sie als Mentorin für die hessischen Universitäten tätig. Sie leitet den Fachbeirat Künstliche Intelligenz und Führung bei der Stiftung Integrata, die sich für die humane Nutzung der IT-Technologie einsetzt, ist Jurymitglied beim Bankengipfel und Mitglied bei der Akademie für neurowissenschaftliches Bildungsmanagement. Sie ist auf allen sozialen Plattformen zu finden und produziert dort nicht nur regelmäßig Blogartikel & tweets, sondern auch Podcasts.   Themen In den Podcastfolgen 156 und 157 konnte ich mit Barbara Liebermeister (Managementberaterin, Buchautorin und Rednerin) über Führung im Digitalen Raum sprechen. Da Führungskräfte auch immer eine Vorbildfunktion haben, sind wir im Gespräch darauf eingegangen. Die Frage: “was müssen Führungskräfte tun, um dieser Vorbildfunktion gerecht zu werden” haben genauer beleuchtet. Ich bedanke mich ganz herzlich bei Barbara für das sehr gute Gespräch und die vielen guten Anregungen und Kernbotschaften zum Thema.  Führung im Digitalen Raum als Vorbild: Kompetenz wird heute insbesondere über digitale Fußspuren abgebildet  Frage: wo sind Deine digitalen Fußspuren als Führungskraft? Für Führungskräfte gilt: es gibt keinen privaten Raum im Internet (alles was Du tust und auch nicht tust (also keine oder schlechte digitale Präsenz), wird bewertet und auf Dein Bild als Führungskraft projeziert! Zeigt Euch im digitalen Raum (für die Mitarbeitenden, für die Kunden und Partner des Unternehmens) Kunden, Partner, Mitarbeitende suchen Informationen zu Führungskräften heute nahezu ausschließlich im Internet (Webseiten, Social Media Kanäle) - Einstieg über Google! Wo bist Du zu finden? Was finde ich dort über Dich? Passt das zu dem, was Du repräsentieren möchtest? Achte auf den “Halo”-Effekt (passt Dein Erscheinungsbild - Dein Foto und Aussehen, Deine Kleidung, etc. zu Deiner Positionierung, also zu dem was Du sagst, postest, verkörperst und wie Du auftrittst?) Zwei Kriterien für die Präsenz im digitalen Raum sende bzw. poste nichts, was Du nicht auch auf einer Bühne vor x-tausend Menschen sagen würdest zahlt dieser Post bzw. die Message, die ich versende, auf mein berufliches Image ein? Agiere vor der Kamera in Online-Meetings mit mehr als 100% - Energieräuber beachten - wenn Du eher introvertiert bist, dann binde eher extrovertierte Menschen aus Deinem Team in die Moderation und die Durchführung von Online-Meetings ein! Teamführung vs. Aufgabenverteilung Rechner aufklappen und Online-Meetings machen reicht nicht Was ist das Ziel des Meetings, wie soll das Meeting ablaufen, was soll hängenbleiben (an Informationen) Sorge bei Online-Meetings für Abwechslung, für Überraschungseffekte und für Humor, binde Teammitglieder ein und übergebe Ihnen z.B. die Vorbereitung oder Moderation von Online-Meetings, sorge für gute Stimmung und Emotionen Merke: Content ist wichtig - der Rahmen, um den Content zu platzieren, ist meistens noch wichtiger! Führe überdurchschnittlich mehr 1:1 Meetings mit Deinen Mitarbeitenden, denn wenn Präsenztreffen im Moment und in den nächsten Monaten nicht möglich sind, ist nur so eine enge und wirkungsvolle Kommunikation möglich Mache „Dailys“ - also kurze 10 Minuten Meetings mit Deinem Team (und empfehle das auch den Führungskräften in Deinem Team) an jedem Morgen z.B. um 09.00 oder 09.30Uhr und stimme alle Personen positiv ein - Hier geht es um gute Laune und positive Stimmung! Tipps zur Umsetzung - wie starte ich als Führungskraft? Tipp 1: stell Dir einfach mal folgende Fragen: Was bringt mir der Digitale Raum in der Zukunft? Welche Optionen bieten sich für mich? Wie (ggfs. auch mit externer Hilfe) könnte ich das hinbekommen? Tipp 2:  Mach standardmäßig Meetings mit Deinem Team und fordere Deine Teammitglieder einfach mal auf, einmal pro Woche oder Monat oder Quartal innovative Vorschläge für die Positionierung im Digitalen Raum zu machen (also Inhalte, Medien, digitale Kanäle, etc.)   #Digitalefuehrung #Digitalleadership #Vorbildsfunktion #Haloeffekt #Gaintalentspodcast   Shownotes Links - Barbara Liebermeister Website - https://barbara-liebermeister.com/ Buch “Die Führungskraft als Influencer” - https://www.amazon.de/Die-F%C3%BChrungskraft-als-Influencer-Follower-ebook/dp/B08837VVDQ LinkedIn - https://www.linkedin.com/in/bliebermeister/ Business Personalities -  http://business-personalities.com/barbara-liebermeister/ Institut für Führungskultur im digitalen Zeitalter -  https://ifidz.de/author/barbara/ Podcast  Spotify: https://open.spotify.com/show/5lLCMVDwBGvwkV5AUqebwZ?si=O-wBbSBWQsexqcq9Q_8esQ Apple: https://podcasts.apple.com/us/podcast/digital-ist-egal-was-z%C3%A4hlt-bist-du/id1454539690   Links Hans-Heinz Wisotzky:  Webseite - www.gaintalents.com LinkedIn -  https://www.linkedin.com/in/hansheinzwisotzky/ XING - https://www.xing.com/profile/HansHeinz_Wisotzky/cv Facebook - https://www.facebook.com/GainTalents Instagram - https://www.instagram.com/gain.talents/ Youtube - https://bit.ly/2GnWMFg

Barbara Liebermeister ist Managementberaterin, Buchautorin und Rednerin. Sie begann ihre berufliche Karriere im Marketing internationaler Konzerne (u. a. Christian Dior, L'Oréal und Hoechst). Ihre Schwerpunktthemen sind Leadership, (Selbst-)Führung und Beziehungsmanagement im digitalen Zeitalter. Sie berät und coacht vorrangig Führungskräfte und angehende Führungskräfte von Start-up-Unternehmen bis hin zum Dax-Konzern – jeweils abgestimmt auf deren individuellen Businessalltag und Bedarf. Barbara Liebermeister ist Gründerin und Leiterin des Instituts für Führungskultur im digitalen Zeitalter (IFIDZ), Frankfurt am Main. Das Institut erforscht und fördert die Management- und Führungskultur im Zeichen der Digitalisierung und entwickelt Methoden, mit denen die Digital- und die Führungsreife der Führungskräfte nachhaltig gesteigert werden können. Sie ist Dozentin an folgenden Hochschulen: RWTH Aachen, Hochschule Kempten und an der Bucerius Law School in Hamburg. Gleichzeitig ist sie als Mentorin für die hessischen Universitäten tätig. Sie leitet den Fachbeirat Künstliche Intelligenz und Führung bei der Stiftung Integrata, die sich für die humane Nutzung der IT-Technologie einsetzt, ist Jurymitglied beim Bankengipfel und Mitglied bei der Akademie für neurowissenschaftliches Bildungsmanagement. Sie ist auf allen sozialen Plattformen zu finden und produziert dort nicht nur regelmäßig Blogartikel & tweets, sondern auch Podcasts.   Themen In den Podcastfolgen 156 und 157 konnte ich mit Barbara Liebermeister (Managementberaterin, Buchautorin und Rednerin) über Führung im Digitalen Raum sprechen. Da Führungskräfte auch immer eine Vorbildfunktion haben, sind wir im Gespräch darauf eingegangen. Die Frage: “was müssen Führungskräfte tun, um dieser Vorbildfunktion gerecht zu werden” haben genauer beleuchtet. Ich bedanke mich ganz herzlich bei Barbara für das sehr gute Gespräch und die vielen guten Anregungen und Kernbotschaften zum Thema.  Führung im Digitalen Raum als Vorbild: Kompetenz wird heute insbesondere über digitale Fußspuren abgebildet  Frage: wo sind Deine digitalen Fußspuren als Führungskraft? Für Führungskräfte gilt: es gibt keinen privaten Raum im Internet (alles was Du tust und auch nicht tust (also keine oder schlechte digitale Präsenz), wird bewertet und auf Dein Bild als Führungskraft projeziert! Zeigt Euch im digitalen Raum (für die Mitarbeitenden, für die Kunden und Partner des Unternehmens) Kunden, Partner, Mitarbeitende suchen Informationen zu Führungskräften heute nahezu ausschließlich im Internet (Webseiten, Social Media Kanäle) - Einstieg über Google! Wo bist Du zu finden? Was finde ich dort über Dich? Passt das zu dem, was Du repräsentieren möchtest? Achte auf den “Halo”-Effekt (passt Dein Erscheinungsbild - Dein Foto und Aussehen, Deine Kleidung, etc. zu Deiner Positionierung, also zu dem was Du sagst, postest, verkörperst und wie Du auftrittst?) Zwei Kriterien für die Präsenz im digitalen Raum sende bzw. poste nichts, was Du nicht auch auf einer Bühne vor x-tausend Menschen sagen würdest zahlt dieser Post bzw. die Message, die ich versende, auf mein berufliches Image ein? Agiere vor der Kamera in Online-Meetings mit mehr als 100% - Energieräuber beachten - wenn Du eher introvertiert bist, dann binde eher extrovertierte Menschen aus Deinem Team in die Moderation und die Durchführung von Online-Meetings ein! Teamführung vs. Aufgabenverteilung Rechner aufklappen und Online-Meetings machen reicht nicht Was ist das Ziel des Meetings, wie soll das Meeting ablaufen, was soll hängenbleiben (an Informationen) Sorge bei Online-Meetings für Abwechslung, für Überraschungseffekte und für Humor, binde Teammitglieder ein und übergebe Ihnen z.B. die Vorbereitung oder Moderation von Online-Meetings, sorge für gute Stimmung und Emotionen Merke: Content ist wichtig - der Rahmen, um den Content zu platzieren, ist meistens noch wichtiger! Führe überdurchschnittlich mehr 1:1 Meetings mit Deinen Mitarbeitenden, denn wenn Präsenztreffen im Moment und in den nächsten Monaten nicht möglich sind, ist nur so eine enge und wirkungsvolle Kommunikation möglich Mache „Dailys“ - also kurze 10 Minuten Meetings mit Deinem Team (und empfehle das auch den Führungskräften in Deinem Team) an jedem Morgen z.B. um 09.00 oder 09.30Uhr und stimme alle Personen positiv ein - Hier geht es um gute Laune und positive Stimmung! Tipps zur Umsetzung - wie starte ich als Führungskraft? Tipp 1: stell Dir einfach mal folgende Fragen: Was bringt mir der Digitale Raum in der Zukunft? Welche Optionen bieten sich für mich? Wie (ggfs. auch mit externer Hilfe) könnte ich das hinbekommen? Tipp 2:  Mach standardmäßig Meetings mit Deinem Team und fordere Deine Teammitglieder einfach mal auf, einmal pro Woche oder Monat oder Quartal innovative Vorschläge für die Positionierung im Digitalen Raum zu machen (also Inhalte, Medien, digitale Kanäle, etc.)   #Digitalefuehrung #Digitalleadership #Vorbildsfunktion #Haloeffekt #Gaintalentspodcast   Shownotes Links - Barbara Liebermeister Website - https://barbara-liebermeister.com/ Buch “Die Führungskraft als Influencer” - https://www.amazon.de/Die-F%C3%BChrungskraft-als-Influencer-Follower-ebook/dp/B08837VVDQ LinkedIn - https://www.linkedin.com/in/bliebermeister/ Business Personalities -  http://business-personalities.com/barbara-liebermeister/ Institut für Führungskultur im digitalen Zeitalter -  https://ifidz.de/author/barbara/ Podcast  Spotify: https://open.spotify.com/show/5lLCMVDwBGvwkV5AUqebwZ?si=O-wBbSBWQsexqcq9Q_8esQ Apple: https://podcasts.apple.com/us/podcast/digital-ist-egal-was-z%C3%A4hlt-bist-du/id1454539690   Links Hans-Heinz Wisotzky:  Webseite - www.gaintalents.com LinkedIn -  https://www.linkedin.com/in/hansheinzwisotzky/ XING - https://www.xing.com/profile/HansHeinz_Wisotzky/cv Facebook - https://www.facebook.com/GainTalents Instagram - https://www.instagram.com/gain.talents/ Youtube - https://bit.ly/2GnWMFg

Barbara Liebermeister ist Managementberaterin, Buchautorin und Rednerin. Sie begann ihre berufliche Karriere im Marketing internationaler Konzerne (u. a. Christian Dior, L'Oréal und Hoechst). Ihre Schwerpunktthemen sind Leadership, (Selbst-)Führung und Beziehungsmanagement im digitalen Zeitalter. Sie berät und coacht vorrangig Führungskräfte und angehende Führungskräfte von Start-up-Unternehmen bis hin zum Dax-Konzern – jeweils abgestimmt auf deren individuellen Businessalltag und Bedarf. Barbara Liebermeister ist Gründerin und Leiterin des Instituts für Führungskultur im digitalen Zeitalter (IFIDZ), Frankfurt am Main. Das Institut erforscht und fördert die Management- und Führungskultur im Zeichen der Digitalisierung und entwickelt Methoden, mit denen die Digital- und die Führungsreife der Führungskräfte nachhaltig gesteigert werden können. Sie ist Dozentin an folgenden Hochschulen: RWTH Aachen, Hochschule Kempten und an der Bucerius Law School in Hamburg. Gleichzeitig ist sie als Mentorin für die hessischen Universitäten tätig. Sie leitet den Fachbeirat Künstliche Intelligenz und Führung bei der Stiftung Integrata, die sich für die humane Nutzung der IT-Technologie einsetzt, ist Jurymitglied beim Bankengipfel und Mitglied bei der Akademie für neurowissenschaftliches Bildungsmanagement. Sie ist auf allen sozialen Plattformen zu finden und produziert dort nicht nur regelmäßig Blogartikel & tweets, sondern auch Podcasts.   Themen In den Podcastfolgen 156 und 157 konnte ich mit Barbara Liebermeister (Managementberaterin, Buchautorin und Rednerin) über Führung im Digitalen Raum sprechen. Da Führungskräfte auch immer eine Vorbildfunktion haben, sind wir im Gespräch darauf eingegangen. Die Frage: “was müssen Führungskräfte tun, um dieser Vorbildfunktion gerecht zu werden” haben genauer beleuchtet. Ich bedanke mich ganz herzlich bei Barbara für das sehr gute Gespräch und die vielen guten Anregungen und Kernbotschaften zum Thema.  Führung im Digitalen Raum als Vorbild: Kompetenz wird heute insbesondere über digitale Fußspuren abgebildet  Frage: wo sind Deine digitalen Fußspuren als Führungskraft? Für Führungskräfte gilt: es gibt keinen privaten Raum im Internet (alles was Du tust und auch nicht tust (also keine oder schlechte digitale Präsenz), wird bewertet und auf Dein Bild als Führungskraft projeziert! Zeigt Euch im digitalen Raum (für die Mitarbeitenden, für die Kunden und Partner des Unternehmens) Kunden, Partner, Mitarbeitende suchen Informationen zu Führungskräften heute nahezu ausschließlich im Internet (Webseiten, Social Media Kanäle) - Einstieg über Google! Wo bist Du zu finden? Was finde ich dort über Dich? Passt das zu dem, was Du repräsentieren möchtest? Achte auf den “Halo”-Effekt (passt Dein Erscheinungsbild - Dein Foto und Aussehen, Deine Kleidung, etc. zu Deiner Positionierung, also zu dem was Du sagst, postest, verkörperst und wie Du auftrittst?) Zwei Kriterien für die Präsenz im digitalen Raum sende bzw. poste nichts, was Du nicht auch auf einer Bühne vor x-tausend Menschen sagen würdest zahlt dieser Post bzw. die Message, die ich versende, auf mein berufliches Image ein? Agiere vor der Kamera in Online-Meetings mit mehr als 100% - Energieräuber beachten - wenn Du eher introvertiert bist, dann binde eher extrovertierte Menschen aus Deinem Team in die Moderation und die Durchführung von Online-Meetings ein! Teamführung vs. Aufgabenverteilung Rechner aufklappen und Online-Meetings machen reicht nicht Was ist das Ziel des Meetings, wie soll das Meeting ablaufen, was soll hängenbleiben (an Informationen) Sorge bei Online-Meetings für Abwechslung, für Überraschungseffekte und für Humor, binde Teammitglieder ein und übergebe Ihnen z.B. die Vorbereitung oder Moderation von Online-Meetings, sorge für gute Stimmung und Emotionen Merke: Content ist wichtig - der Rahmen, um den Content zu platzieren, ist meistens noch wichtiger! Führe überdurchschnittlich mehr 1:1 Meetings mit Deinen Mitarbeitenden, denn wenn Präsenztreffen im Moment und in den nächsten Monaten nicht möglich sind, ist nur so eine enge und wirkungsvolle Kommunikation möglich Mache „Dailys“ - also kurze 10 Minuten Meetings mit Deinem Team (und empfehle das auch den Führungskräften in Deinem Team) an jedem Morgen z.B. um 09.00 oder 09.30Uhr und stimme alle Personen positiv ein - Hier geht es um gute Laune und positive Stimmung! Tipps zur Umsetzung - wie starte ich als Führungskraft? Tipp 1: stell Dir einfach mal folgende Fragen: Was bringt mir der Digitale Raum in der Zukunft? Welche Optionen bieten sich für mich? Wie (ggfs. auch mit externer Hilfe) könnte ich das hinbekommen? Tipp 2:  Mach standardmäßig Meetings mit Deinem Team und fordere Deine Teammitglieder einfach mal auf, einmal pro Woche oder Monat oder Quartal innovative Vorschläge für die Positionierung im Digitalen Raum zu machen (also Inhalte, Medien, digitale Kanäle, etc.)   #Digitalefuehrung #Digitalleadership #Vorbildsfunktion #Haloeffekt #Gaintalentspodcast   Shownotes Links - Barbara Liebermeister Website - https://barbara-liebermeister.com/ Buch “Die Führungskraft als Influencer” - https://www.amazon.de/Die-F%C3%BChrungskraft-als-Influencer-Follower-ebook/dp/B08837VVDQ LinkedIn - https://www.linkedin.com/in/bliebermeister/ Business Personalities -  http://business-personalities.com/barbara-liebermeister/ Institut für Führungskultur im digitalen Zeitalter -  https://ifidz.de/author/barbara/ Podcast  Spotify: https://open.spotify.com/show/5lLCMVDwBGvwkV5AUqebwZ?si=O-wBbSBWQsexqcq9Q_8esQ Apple: https://podcasts.apple.com/us/podcast/digital-ist-egal-was-z%C3%A4hlt-bist-du/id1454539690   Links Hans-Heinz Wisotzky:  Webseite - www.gaintalents.com LinkedIn -  https://www.linkedin.com/in/hansheinzwisotzky/ XING - https://www.xing.com/profile/HansHeinz_Wisotzky/cv Facebook - https://www.facebook.com/GainTalents Instagram - https://www.instagram.com/gain.talents/ Youtube - https://bit.ly/2GnWMFg

Barbara Liebermeister ist Managementberaterin, Buchautorin und Rednerin. Sie begann ihre berufliche Karriere im Marketing internationaler Konzerne (u. a. Christian Dior, L'Oréal und Hoechst). Ihre Schwerpunktthemen sind Leadership, (Selbst-)Führung und Beziehungsmanagement im digitalen Zeitalter. Sie berät und coacht vorrangig Führungskräfte und angehende Führungskräfte von Start-up-Unternehmen bis hin zum Dax-Konzern – jeweils abgestimmt auf deren individuellen Businessalltag und Bedarf. Barbara Liebermeister ist Gründerin und Leiterin des Instituts für Führungskultur im digitalen Zeitalter (IFIDZ), Frankfurt am Main. Das Institut erforscht und fördert die Management- und Führungskultur im Zeichen der Digitalisierung und entwickelt Methoden, mit denen die Digital- und die Führungsreife der Führungskräfte nachhaltig gesteigert werden können. Sie ist Dozentin an folgenden Hochschulen: RWTH Aachen, Hochschule Kempten und an der Bucerius Law School in Hamburg. Gleichzeitig ist sie als Mentorin für die hessischen Universitäten tätig. Sie leitet den Fachbeirat Künstliche Intelligenz und Führung bei der Stiftung Integrata, die sich für die humane Nutzung der IT-Technologie einsetzt, ist Jurymitglied beim Bankengipfel und Mitglied bei der Akademie für neurowissenschaftliches Bildungsmanagement. Sie ist auf allen sozialen Plattformen zu finden und produziert dort nicht nur regelmäßig Blogartikel & tweets, sondern auch Podcasts.   Themen In den Podcastfolgen 156 und 157 konnte ich mit Barbara Liebermeister (Managementberaterin, Buchautorin und Rednerin) über Führung im Digitalen Raum sprechen. Da Führungskräfte auch immer eine Vorbildfunktion haben, sind wir im Gespräch darauf eingegangen. Die Frage: “was müssen Führungskräfte tun, um dieser Vorbildfunktion gerecht zu werden” haben genauer beleuchtet. Ich bedanke mich ganz herzlich bei Barbara für das sehr gute Gespräch und die vielen guten Anregungen und Kernbotschaften zum Thema.  Führung im Digitalen Raum als Vorbild: Kompetenz wird heute insbesondere über digitale Fußspuren abgebildet  Frage: wo sind Deine digitalen Fußspuren als Führungskraft? Für Führungskräfte gilt: es gibt keinen privaten Raum im Internet (alles was Du tust und auch nicht tust (also keine oder schlechte digitale Präsenz), wird bewertet und auf Dein Bild als Führungskraft projeziert! Zeigt Euch im digitalen Raum (für die Mitarbeitenden, für die Kunden und Partner des Unternehmens) Kunden, Partner, Mitarbeitende suchen Informationen zu Führungskräften heute nahezu ausschließlich im Internet (Webseiten, Social Media Kanäle) - Einstieg über Google! Wo bist Du zu finden? Was finde ich dort über Dich? Passt das zu dem, was Du repräsentieren möchtest? Achte auf den “Halo”-Effekt (passt Dein Erscheinungsbild - Dein Foto und Aussehen, Deine Kleidung, etc. zu Deiner Positionierung, also zu dem was Du sagst, postest, verkörperst und wie Du auftrittst?) Zwei Kriterien für die Präsenz im digitalen Raum sende bzw. poste nichts, was Du nicht auch auf einer Bühne vor x-tausend Menschen sagen würdest zahlt dieser Post bzw. die Message, die ich versende, auf mein berufliches Image ein? Agiere vor der Kamera in Online-Meetings mit mehr als 100% - Energieräuber beachten - wenn Du eher introvertiert bist, dann binde eher extrovertierte Menschen aus Deinem Team in die Moderation und die Durchführung von Online-Meetings ein! Teamführung vs. Aufgabenverteilung Rechner aufklappen und Online-Meetings machen reicht nicht Was ist das Ziel des Meetings, wie soll das Meeting ablaufen, was soll hängenbleiben (an Informationen) Sorge bei Online-Meetings für Abwechslung, für Überraschungseffekte und für Humor, binde Teammitglieder ein und übergebe Ihnen z.B. die Vorbereitung oder Moderation von Online-Meetings, sorge für gute Stimmung und Emotionen Merke: Content ist wichtig - der Rahmen, um den Content zu platzieren, ist meistens noch wichtiger! Führe überdurchschnittlich mehr 1:1 Meetings mit Deinen Mitarbeitenden, denn wenn Präsenztreffen im Moment und in den nächsten Monaten nicht möglich sind, ist nur so eine enge und wirkungsvolle Kommunikation möglich Mache „Dailys“ - also kurze 10 Minuten Meetings mit Deinem Team (und empfehle das auch den Führungskräften in Deinem Team) an jedem Morgen z.B. um 09.00 oder 09.30Uhr und stimme alle Personen positiv ein - Hier geht es um gute Laune und positive Stimmung! Tipps zur Umsetzung - wie starte ich als Führungskraft? Tipp 1: stell Dir einfach mal folgende Fragen: Was bringt mir der Digitale Raum in der Zukunft? Welche Optionen bieten sich für mich? Wie (ggfs. auch mit externer Hilfe) könnte ich das hinbekommen? Tipp 2:  Mach standardmäßig Meetings mit Deinem Team und fordere Deine Teammitglieder einfach mal auf, einmal pro Woche oder Monat oder Quartal innovative Vorschläge für die Positionierung im Digitalen Raum zu machen (also Inhalte, Medien, digitale Kanäle, etc.)   #Digitalefuehrung #Digitalleadership #Vorbildsfunktion #Haloeffekt #Gaintalentspodcast   Shownotes Links - Barbara Liebermeister Website - https://barbara-liebermeister.com/ Buch “Die Führungskraft als Influencer” - https://www.amazon.de/Die-F%C3%BChrungskraft-als-Influencer-Follower-ebook/dp/B08837VVDQ LinkedIn - https://www.linkedin.com/in/bliebermeister/ Business Personalities -  http://business-personalities.com/barbara-liebermeister/ Institut für Führungskultur im digitalen Zeitalter -  https://ifidz.de/author/barbara/ Podcast  Spotify: https://open.spotify.com/show/5lLCMVDwBGvwkV5AUqebwZ?si=O-wBbSBWQsexqcq9Q_8esQ Apple: https://podcasts.apple.com/us/podcast/digital-ist-egal-was-z%C3%A4hlt-bist-du/id1454539690   Links Hans-Heinz Wisotzky:  Webseite - www.gaintalents.com LinkedIn -  https://www.linkedin.com/in/hansheinzwisotzky/ XING - https://www.xing.com/profile/HansHeinz_Wisotzky/cv Facebook - https://www.facebook.com/GainTalents Instagram - https://www.instagram.com/gain.talents/ Youtube - https://bit.ly/2GnWMFg

Barbara Liebermeister ist Managementberaterin, Buchautorin und Rednerin. Sie begann ihre berufliche Karriere im Marketing internationaler Konzerne (u. a. Christian Dior, L'Oréal und Hoechst). Ihre Schwerpunktthemen sind Leadership, (Selbst-)Führung und Beziehungsmanagement im digitalen Zeitalter. Sie berät und coacht vorrangig Führungskräfte und angehende Führungskräfte von Start-up-Unternehmen bis hin zum Dax-Konzern – jeweils abgestimmt auf deren individuellen Businessalltag und Bedarf. Barbara Liebermeister ist Gründerin und Leiterin des Instituts für Führungskultur im digitalen Zeitalter (IFIDZ), Frankfurt am Main. Das Institut erforscht und fördert die Management- und Führungskultur im Zeichen der Digitalisierung und entwickelt Methoden, mit denen die Digital- und die Führungsreife der Führungskräfte nachhaltig gesteigert werden können. Sie ist Dozentin an folgenden Hochschulen: RWTH Aachen, Hochschule Kempten und an der Bucerius Law School in Hamburg. Gleichzeitig ist sie als Mentorin für die hessischen Universitäten tätig. Sie leitet den Fachbeirat Künstliche Intelligenz und Führung bei der Stiftung Integrata, die sich für die humane Nutzung der IT-Technologie einsetzt, ist Jurymitglied beim Bankengipfel und Mitglied bei der Akademie für neurowissenschaftliches Bildungsmanagement. Sie ist auf allen sozialen Plattformen zu finden und produziert dort nicht nur regelmäßig Blogartikel & tweets, sondern auch Podcasts.   Themen In den Podcastfolgen 156 und 157 konnte ich mit Barbara Liebermeister (Managementberaterin, Buchautorin und Rednerin) über Führung im Digitalen Raum sprechen. Da Führungskräfte auch immer eine Vorbildfunktion haben, sind wir im Gespräch darauf eingegangen. Die Frage: “was müssen Führungskräfte tun, um dieser Vorbildfunktion gerecht zu werden” haben genauer beleuchtet. Ich bedanke mich ganz herzlich bei Barbara für das sehr gute Gespräch und die vielen guten Anregungen und Kernbotschaften zum Thema.  Führung im Digitalen Raum als Vorbild: Kompetenz wird heute insbesondere über digitale Fußspuren abgebildet  Frage: wo sind Deine digitalen Fußspuren als Führungskraft? Für Führungskräfte gilt: es gibt keinen privaten Raum im Internet (alles was Du tust und auch nicht tust (also keine oder schlechte digitale Präsenz), wird bewertet und auf Dein Bild als Führungskraft projeziert! Zeigt Euch im digitalen Raum (für die Mitarbeitenden, für die Kunden und Partner des Unternehmens) Kunden, Partner, Mitarbeitende suchen Informationen zu Führungskräften heute nahezu ausschließlich im Internet (Webseiten, Social Media Kanäle) - Einstieg über Google! Wo bist Du zu finden? Was finde ich dort über Dich? Passt das zu dem, was Du repräsentieren möchtest? Achte auf den “Halo”-Effekt (passt Dein Erscheinungsbild - Dein Foto und Aussehen, Deine Kleidung, etc. zu Deiner Positionierung, also zu dem was Du sagst, postest, verkörperst und wie Du auftrittst?) Zwei Kriterien für die Präsenz im digitalen Raum sende bzw. poste nichts, was Du nicht auch auf einer Bühne vor x-tausend Menschen sagen würdest zahlt dieser Post bzw. die Message, die ich versende, auf mein berufliches Image ein? Agiere vor der Kamera in Online-Meetings mit mehr als 100% - Energieräuber beachten - wenn Du eher introvertiert bist, dann binde eher extrovertierte Menschen aus Deinem Team in die Moderation und die Durchführung von Online-Meetings ein! Teamführung vs. Aufgabenverteilung Rechner aufklappen und Online-Meetings machen reicht nicht Was ist das Ziel des Meetings, wie soll das Meeting ablaufen, was soll hängenbleiben (an Informationen) Sorge bei Online-Meetings für Abwechslung, für Überraschungseffekte und für Humor, binde Teammitglieder ein und übergebe Ihnen z.B. die Vorbereitung oder Moderation von Online-Meetings, sorge für gute Stimmung und Emotionen Merke: Content ist wichtig - der Rahmen, um den Content zu platzieren, ist meistens noch wichtiger! Führe überdurchschnittlich mehr 1:1 Meetings mit Deinen Mitarbeitenden, denn wenn Präsenztreffen im Moment und in den nächsten Monaten nicht möglich sind, ist nur so eine enge und wirkungsvolle Kommunikation möglich Mache „Dailys“ - also kurze 10 Minuten Meetings mit Deinem Team (und empfehle das auch den Führungskräften in Deinem Team) an jedem Morgen z.B. um 09.00 oder 09.30Uhr und stimme alle Personen positiv ein - Hier geht es um gute Laune und positive Stimmung! Tipps zur Umsetzung - wie starte ich als Führungskraft? Tipp 1: stell Dir einfach mal folgende Fragen: Was bringt mir der Digitale Raum in der Zukunft? Welche Optionen bieten sich für mich? Wie (ggfs. auch mit externer Hilfe) könnte ich das hinbekommen? Tipp 2:  Mach standardmäßig Meetings mit Deinem Team und fordere Deine Teammitglieder einfach mal auf, einmal pro Woche oder Monat oder Quartal innovative Vorschläge für die Positionierung im Digitalen Raum zu machen (also Inhalte, Medien, digitale Kanäle, etc.)   #Digitalefuehrung #Digitalleadership #Vorbildsfunktion #Haloeffekt #Gaintalentspodcast   Shownotes Links - Barbara Liebermeister Website - https://barbara-liebermeister.com/ Buch “Die Führungskraft als Influencer” - https://www.amazon.de/Die-F%C3%BChrungskraft-als-Influencer-Follower-ebook/dp/B08837VVDQ LinkedIn - https://www.linkedin.com/in/bliebermeister/ Business Personalities -  http://business-personalities.com/barbara-liebermeister/ Institut für Führungskultur im digitalen Zeitalter -  https://ifidz.de/author/barbara/ Podcast  Spotify: https://open.spotify.com/show/5lLCMVDwBGvwkV5AUqebwZ?si=O-wBbSBWQsexqcq9Q_8esQ Apple: https://podcasts.apple.com/us/podcast/digital-ist-egal-was-z%C3%A4hlt-bist-du/id1454539690   Links Hans-Heinz Wisotzky:  Webseite - www.gaintalents.com LinkedIn -  https://www.linkedin.com/in/hansheinzwisotzky/ XING - https://www.xing.com/profile/HansHeinz_Wisotzky/cv Facebook - https://www.facebook.com/GainTalents Instagram - https://www.instagram.com/gain.talents/ Youtube - https://bit.ly/2GnWMFg

Barbara Liebermeister ist Managementberaterin, Buchautorin und Rednerin. Sie begann ihre berufliche Karriere im Marketing internationaler Konzerne (u. a. Christian Dior, L'Oréal und Hoechst). Ihre Schwerpunktthemen sind Leadership, (Selbst-)Führung und Beziehungsmanagement im digitalen Zeitalter. Sie berät und coacht vorrangig Führungskräfte und angehende Führungskräfte von Start-up-Unternehmen bis hin zum Dax-Konzern – jeweils abgestimmt auf deren individuellen Businessalltag und Bedarf. Barbara Liebermeister ist Gründerin und Leiterin des Instituts für Führungskultur im digitalen Zeitalter (IFIDZ), Frankfurt am Main. Das Institut erforscht und fördert die Management- und Führungskultur im Zeichen der Digitalisierung und entwickelt Methoden, mit denen die Digital- und die Führungsreife der Führungskräfte nachhaltig gesteigert werden können. Sie ist Dozentin an folgenden Hochschulen: RWTH Aachen, Hochschule Kempten und an der Bucerius Law School in Hamburg. Gleichzeitig ist sie als Mentorin für die hessischen Universitäten tätig. Sie leitet den Fachbeirat Künstliche Intelligenz und Führung bei der Stiftung Integrata, die sich für die humane Nutzung der IT-Technologie einsetzt, ist Jurymitglied beim Bankengipfel und Mitglied bei der Akademie für neurowissenschaftliches Bildungsmanagement. Sie ist auf allen sozialen Plattformen zu finden und produziert dort nicht nur regelmäßig Blogartikel & tweets, sondern auch Podcasts.   Themen In den Podcastfolgen 156 und 157 konnte ich mit Barbara Liebermeister (Managementberaterin, Buchautorin und Rednerin) über Führung im Digitalen Raum sprechen. Da Führungskräfte auch immer eine Vorbildfunktion haben, sind wir im Gespräch darauf eingegangen. Die Frage: “was müssen Führungskräfte tun, um dieser Vorbildfunktion gerecht zu werden” haben genauer beleuchtet. Ich bedanke mich ganz herzlich bei Barbara für das sehr gute Gespräch und die vielen guten Anregungen und Kernbotschaften zum Thema.  Führung im Digitalen Raum als Vorbild: Kompetenz wird heute insbesondere über digitale Fußspuren abgebildet  Frage: wo sind Deine digitalen Fußspuren als Führungskraft? Für Führungskräfte gilt: es gibt keinen privaten Raum im Internet (alles was Du tust und auch nicht tust (also keine oder schlechte digitale Präsenz), wird bewertet und auf Dein Bild als Führungskraft projeziert! Zeigt Euch im digitalen Raum (für die Mitarbeitenden, für die Kunden und Partner des Unternehmens) Kunden, Partner, Mitarbeitende suchen Informationen zu Führungskräften heute nahezu ausschließlich im Internet (Webseiten, Social Media Kanäle) - Einstieg über Google! Wo bist Du zu finden? Was finde ich dort über Dich? Passt das zu dem, was Du repräsentieren möchtest? Achte auf den “Halo”-Effekt (passt Dein Erscheinungsbild - Dein Foto und Aussehen, Deine Kleidung, etc. zu Deiner Positionierung, also zu dem was Du sagst, postest, verkörperst und wie Du auftrittst?) Zwei Kriterien für die Präsenz im digitalen Raum sende bzw. poste nichts, was Du nicht auch auf einer Bühne vor x-tausend Menschen sagen würdest zahlt dieser Post bzw. die Message, die ich versende, auf mein berufliches Image ein? Agiere vor der Kamera in Online-Meetings mit mehr als 100% - Energieräuber beachten - wenn Du eher introvertiert bist, dann binde eher extrovertierte Menschen aus Deinem Team in die Moderation und die Durchführung von Online-Meetings ein! Teamführung vs. Aufgabenverteilung Rechner aufklappen und Online-Meetings machen reicht nicht Was ist das Ziel des Meetings, wie soll das Meeting ablaufen, was soll hängenbleiben (an Informationen) Sorge bei Online-Meetings für Abwechslung, für Überraschungseffekte und für Humor, binde Teammitglieder ein und übergebe Ihnen z.B. die Vorbereitung oder Moderation von Online-Meetings, sorge für gute Stimmung und Emotionen Merke: Content ist wichtig - der Rahmen, um den Content zu platzieren, ist meistens noch wichtiger! Führe überdurchschnittlich mehr 1:1 Meetings mit Deinen Mitarbeitenden, denn wenn Präsenztreffen im Moment und in den nächsten Monaten nicht möglich sind, ist nur so eine enge und wirkungsvolle Kommunikation möglich Mache „Dailys“ - also kurze 10 Minuten Meetings mit Deinem Team (und empfehle das auch den Führungskräften in Deinem Team) an jedem Morgen z.B. um 09.00 oder 09.30Uhr und stimme alle Personen positiv ein - Hier geht es um gute Laune und positive Stimmung! Tipps zur Umsetzung - wie starte ich als Führungskraft? Tipp 1: stell Dir einfach mal folgende Fragen: Was bringt mir der Digitale Raum in der Zukunft? Welche Optionen bieten sich für mich? Wie (ggfs. auch mit externer Hilfe) könnte ich das hinbekommen? Tipp 2:  Mach standardmäßig Meetings mit Deinem Team und fordere Deine Teammitglieder einfach mal auf, einmal pro Woche oder Monat oder Quartal innovative Vorschläge für die Positionierung im Digitalen Raum zu machen (also Inhalte, Medien, digitale Kanäle, etc.)   #Digitalefuehrung #Digitalleadership #Vorbildsfunktion #Haloeffekt #Gaintalentspodcast   Shownotes Links - Barbara Liebermeister Website - https://barbara-liebermeister.com/ Buch “Die Führungskraft als Influencer” - https://www.amazon.de/Die-F%C3%BChrungskraft-als-Influencer-Follower-ebook/dp/B08837VVDQ LinkedIn - https://www.linkedin.com/in/bliebermeister/ Business Personalities -  http://business-personalities.com/barbara-liebermeister/ Institut für Führungskultur im digitalen Zeitalter -  https://ifidz.de/author/barbara/ Podcast  Spotify: https://open.spotify.com/show/5lLCMVDwBGvwkV5AUqebwZ?si=O-wBbSBWQsexqcq9Q_8esQ Apple: https://podcasts.apple.com/us/podcast/digital-ist-egal-was-z%C3%A4hlt-bist-du/id1454539690   Links Hans-Heinz Wisotzky:  Webseite - www.gaintalents.com LinkedIn -  https://www.linkedin.com/in/hansheinzwisotzky/ XING - https://www.xing.com/profile/HansHeinz_Wisotzky/cv Facebook - https://www.facebook.com/GainTalents Instagram - https://www.instagram.com/gain.talents/ Youtube - https://bit.ly/2GnWMFg

Pessimism of the Intellect, Optimism of the Will Bill Gates Partnered Chinese To Conduct Gain-Of-Function Research Delta Variant Far Less Deadly than Previous Variants, According to TrialSite Analysis CDC and Media Say 61% of Americans are Vaxxed, but Data Shows it is 32% What Will Segregated Society Look Like for the Unvaxxed? IPCC climate report: Profound changes are underway in Earth's oceans and ice – a lead author explains what the warnings mean Ohio judge orders man to get a COVID-19 vaccine as part of his sentence Youth, the pandemic and a global mental health crisis A Different World Order   Today's Videos 1.  Vaccine Stories  2. A MESSAGE TO THE EDINBURG CISD SCHOOL BOARD 3.AGUIRRE HAWAII COVID WHISTLEBLOWER 4. ARE PEOPLE DYING MISDIAGNOSED? DR. BRYAN ARDIS, DR. REINER FUELLMICH AND DR. WOLFGANG WODARG   Strawberries improve cognition in a randomized, double-blind, placebo-controlled trial of older adults Tufts University, August 8, 2021 According to news originating from Boston, Massachusetts, research stated, “Functional changes in the brain during ageing can alter learning and memory, gait and balance - in some cases leading to early cognitive decline, disability or injurious falls among older adults. Dietary interventions with strawberry (SB) have been associated with improvements in neuronal, psychomotor and cognitive functions in rodent models of ageing.” Our news journalists obtained a quote from the research from Tufts University, “We hypothesised that dietary supplementation with SB would improve mobility and cognition among older adults. In this study, twenty-two men and fifteen women, between the ages of 60 and 75 years, were recruited into a randomised, double-blind, placebo-controlled trial in which they consumed either freeze-dried SB (24 g/d, equivalent to two cups of fresh SB) or a SB placebo for 90 d. Participants completed a battery of balance, gait and cognitive tests at baseline and again at 45 and 90 d of intervention. Significant supplement group by study visit interactions were observed on tests of learning and memory. Participants in the SB group showed significantly shorter latencies in a virtual spatial navigation task (P = 0.020,.p2 = 0.106) and increased word recognition in the California Verbal Learning test (P = 0.014,.p2 = 0.159) across study visits relative to controls. However, no improvement in gait or balance was observed.” According to the news editors, the research concluded: “These findings show that the addition of SB to the diets of healthy, older adults can improve some aspects of cognition, but not gait or balance, although more studies with a larger sample size and longer follow-up are needed to confirm this finding.” This research has been peer-reviewed.   Growing evidence of vitamin K benefits for heart health Edith Cowan University (Australia), August 10, 2021 New Edith Cowan University (ECU) research has found that people who eat a diet rich in vitamin K have up to a 34 percent lower risk of atherosclerosis-related cardiovascular disease (conditions affecting the heart or blood vessels). Researchers examined data from more than 50,000 people taking part in the Danish Diet, Cancer, and Health study over a 23-year period. They investigated whether people who ate more foods containing vitamin K had a lower risk of cardiovascular disease related to atherosclerosis (plaque build-up in the arteries). There are two types of vitamin K found in foods we eat: vitamin K1 comes primarily from green leafy vegetables and vegetable oils while vitamin K2 is found in meat, eggs and fermented foods such as cheese. The study found that people with the highest intakes of vitamin K1 were 21 percent less likely to be hospitalized with cardiovascular disease related to atherosclerosis. For vitamin K2, the risk of being hospitalized was 14 percent lower. This lower risk was seen for all types of heart disease related to atherosclerosis, particularly for peripheral artery disease at 34 percent. ECU researcher and senior author on the study Dr. Nicola Bondonno said the findings suggest that consuming more vitamin K may be important for protection against atherosclerosis and subsequent cardiovascular disease. "Current dietary guidelines for the consumption of vitamin K are generally only based on the amount of vitamin K1 a person should consume to ensure that their blood can coagulate," she said. "However, there is growing evidence that intakes of vitamin K above the current guidelines can afford further protection against the development of other diseases, such as atherosclerosis. "Although more research is needed to fully understand the process, we believe that vitamin K works by protecting against the calcium build-up in the major arteries of the body leading to vascular calcification." University of Western Australia researcher Dr. Jamie Bellinge, the first author on the study, said the role of vitamin K in cardiovascular health and particularly in vascular calcification is an area of research offering promising hope for the future. "Cardiovascular disease remains a leading cause of death in Australia and there's still a limited understanding of the importance of different vitamins found in foodand their effect on heart attacks, strokes and peripheral artery disease," Dr. Bellinge said. "These findings shed light on the potentially important effect that vitamin K has on the killer disease and reinforces the importance of a healthy diet in preventing it." Dr. Bondonno said that while databases on the vitamin K1 content of foods are very comprehensive, there is currently much less data on the vitamin K2 content of foods. Furthermore, there are 10 forms of vitamin K2 found in our diet and each of these may be absorbed and act differently within our bodies. "The next phase of the research will involve developing and improving databases on the vitamin K2 content of foods. "More research into the different dietary sources and effects of different types of vitamin K2 is a priority," Dr. Bondonno said. Additionally, there is a need for an Australian database on the vitamin K content of Australian foods (e.g. vegemite and kangaroo). To address this need, Dr. Marc Sim, a collaborator on the study, has just finished developing an Australian database on the vitamin K content of foods which will be published soon. The paper "Vitamin K intake and atherosclerotic cardiovascular disease in the Danish Diet Cancer and Health Study' was published in the Journal of the American Heart Association. High BMI causes depression, both physical and social factors play a role University of Exeter (UK), August 9, 2021 A large-scale study provides further evidence that being overweight causes depression and lowers wellbeing and indicates both social and physical factors may play a role in the effect. With one in four adults estimated to be obese in the UK, and growing numbers of children affected, obesity is a global health challenge. While the dangers of being obese on physical health is well known, researchers are now discovering that being overweight can also have a significant impact on mental health.  The new study, published in Human Molecular Genetics, sought to investigate why a body of evidence now indicates that higher BMI causes depression. The team used genetic analysis, known as Mendelian Randomisation, to examine whether the causal link is the result of psychosocial pathways, such as societal influences and social stigma, or physical pathways, such as metabolic conditions linked to higher BMI. Such conditions include high blood pressure, type 2 diabetes and cardiovascular disease. In research led by the University of Exeter and funded by the Academy of Medical Sciences, the team examined genetic data from more than 145,000 participants from the UK Biobank with detailed mental health data available. In a multifaceted study, the researchers analyzed genetic variants linked to higher BMI, as well as outcomes from a clinically-relevant mental health questionnaire designed to assess levels of depression, anxiety and wellbeing. To examine which pathways may be active in causing depression in people with higher BMI, the team also interrogated two sets of previously discovered genetic variants. One set of genes makes people fatter, yet metabolically healthier, meaning they were less likely to develop conditions linked to higher BMI, such as high blood pressure and type 2 diabetes. The second set of genes analyzed make people fatter and metabolically unhealthy, or more prone to such conditions. The team found little difference between the two sets of genetic variants, indicating that both physical and social factors play a role in higher rates of depression and poorer wellbeing. Lead author Jess O'Loughlin, at the University of Exeter Medical School, said: "Obesity and depression are both major global health challenges, and our study provides the most robust evidence to date that higher BMI causes depression. Understanding whether physical or social factors are responsible for this relationship can help inform effective strategies to improve mental health and wellbeing. Our research suggests that being fatter leads to a higher risk of depression, regardless of the role of metabolic health. This suggests that both physical health and social factors, such as social stigma, both play a role in the relationship between obesity and depression." Lead author Dr. Francesco Casanova, of the University of Exeter Medical School, said, "This is a robust study, made possible by the quality of UK Biobank data. Our research adds to a body of evidence that being overweight causes depression. Finding ways to support people to lose weight could benefit their mental health as well as their physical health." The study, titled "Higher adiposity and mental health: causal inference using Mendelian Randomisation," is published in Human Molecular Genetics.   Protective effects of saffron compound against amyloid beta-induced neurotoxicity Guangdong Medical University (China), August 4, 2021 According to news reporting from Dongguan, People's Republic of China, research stated, “Alzheimer's disease (AD) is a most common neurodegenerative disorder worldwide. Because of its complex pathogenesis, the prevention and therapies of AD still are a severe challenge.” The news correspondents obtained a quote from the research from Guangdong Medical University, “Evidence suggested that crocin, the major component of saffron, exhibited neuroprotective effects in AD. As such, in this study, N2a/APP695swe cells were enrolled to investigate the effects of crocin on endogenous A beta-induced neurotoxicity. Crocin (100 and 200 mu M) could ameliorate cytotoxicity according to CCK-8 assay and reduce apoptosis in line with Hoechst 33,342 staining and Annexin V-FITC/PI double staining in N2a/APP695swe cells. Reduced ROS generation and elevated MMP were found in N2a/APP695swe cells treated with crocin (100 and 200 mu M). Additionally, crocin at concentrations of 100 and 200 mu M inhibited the release of cytochrome and attenuated caspases-3 activity in N2a/APP695swe cells. Furthermore, succinylation, crotonylation, 2-hydroxyisobutyrylation, malonylation, and phosphorylation were significantly reduced, while a slight increase of acetylation was found in 100-mu M crocin treated N2a/APP695swe cells.” According to the news reporters, the research concluded: “Taken together, crocin may be a promising natural product candidate for the effective cure of AD.” This research has been peer-reviewed.   Microbes have potential to reverse aging in the brain University College Cork (Ireland), August 10, 2021 Microbiome Ireland, a world leading SFI Research Centre, have found that aging-associated changes in the immune system of old mice were reversed by the transfer of gut microbiota from the young mice. The researchers saw improved behavior of older mice in several cognitive tests for learning, memory and anxiety. Credit: Clare Keogh Research from APC Microbiome Ireland (APC) at University College Cork (UCC) published today in the leading international scientific journal Nature Agingintroduces a novel approach to reverse aspects of aging-related deterioration in the brain and cognitive function via the microbes in the gut. As our population ages one of the key global challenges is to develop strategies to maintain healthy brain function. This ground-breaking  research opens up a potentially new therapeutic avenues  in the form of microbial-based interventions to slow down brain aging and associated cognitive problems.  The work was carried out by researchers in the Brain-Gut-Microbiota lab in APC led by Prof John F. Cryan, Vice President for Research & Innovation, University College Cork as well as a Principal Investigator at APC Microbiome Ireland  an SFI Research Centre,  based in in University College Cork and Teagasc Moorepark. There is a growing appreciation of the importance of the microbes in the gut on all aspects of physiology and medicine. In this latest mouse study the authors show that by transplanting microbes from young into old animals they could rejuvenate aspects of brain and immune function. Prof John F. Cryan, says "Previous research published by the APC and other groups internationally has shown that the  gut microbiome plays a key role in aging and the aging process. This new research is a potential game changer , as we have established that the microbiome can be harnessed to reverse age-related brain deterioration. We also see evidence of improved learning ability and cognitive function". Although very exciting Cryan cautions that "it is still early days and much more work is needed to see how these findings could be translated in humans".   APC Director Prof Paul Ross stated that "This research of Prof. Cryan and colleagues further demonstrates the importance of the gut microbiome in many aspects of health, and particularly across across the brain/gut axis where brain functioning can be positively influenced. The study opens up possibilities in the future to modulate gut microbiota as a therapeutic target to influence brain health" The study was led by co-first authors Dr. Marcus Boehme along with Ph.D. students Katherine E. Guzzetta, and Thomaz Bastiaansen. Even quick meditation aids cognitive skills Yale University & Swarthmore College, August 7, 2018  College students who listen to a 10-minute meditation tape complete simple cognitive tasks more quickly and accurately than peers who listen to a "control" recording on a generic subject, researchers at Yale University and Swarthmore College report. The study, published in the journal Frontiers of Neuroscience, shows even people who have never meditated before can benefit from even a short meditation practice. "We have known for awhile that people who practice meditation for a few weeks or months tend to perform better on cognitive tests, but now we know you don't have to spend weeks practicing to see improvement," said Yale's Hedy Kober, associate professor of psychiatry and psychology and senior author of the study. The research team headed by Kober and Catherine Norris at Swarthmore randomly divided college students into two groups. One group listened to a 10-minute recording on meditation prior to performing cognitive tests and the second group listened to a similarly produced tape about sequoia trees. Both groups were then given simple tasks designed to measure cognitive dexterity. Those who listened to the meditation recording performed significantly better, across two studies. There was one exception, however. Those who scored highest in measurements of neuroticism—"I worry all the time"—did not benefit from listening to the meditation tape. "We don't know if longer meditation sessions, or multiple sessions, would improve their cognitive scores, and we look forward to testing that in future studies," Kober said.   Physical activity protects children from the adverse effects of digital media on their weight later in adolescence University of Helsinki (Finland), August 9, 2021   Children's heavy digital media use is associated with a risk of being overweight later in adolescence. Physical activity protects children from the adverse effects of digital media on their weight later in adolescence. A recently completed study shows that six hours of leisure-time physical activity per week at the age of 11 reduces the risk of being overweight at 14 years of age associated with heavy use of digital media. Obesity in children and adolescents is one of the most significant health-related challenges globally. A study carried out by the Folkhälsan Research Center and the University of Helsinki investigated whether a link exists between the digital media use of Finnish school-age children and the risk of being overweight later in adolescence. In addition, the study looked into whether children's physical activity has an effect on this potential link. The results were published in the Journal of Physical Activity and Health. More than six hours of physical activity per week appears to reverse adverse effects of screen time The study involved 4,661 children from the Finnish Health in Teens (Fin-HIT) study. The participating children reported how much time they spent on sedentary digital media use and physical activity outside school hours. The study demonstrated that heavy use of digital media at 11 years of age was associated with a heightened risk of being overweight at 14 years of age in children who reported engaging in under six hours per week of physical activity in their leisure time. In children who reported being physically active for six or more hours per week, such a link was not observed. The study also took into account other factors potentially impacting obesity, such as childhood eating habits and the amount of sleep, as well as the amount of digital media use and physical activity in adolescence. In spite of the confounding factors, the protective role of childhood physical activity in the connection between digital media use in childhood and being overweight later in life was successfully confirmed. "The effect of physical activity on the association between digital media use and being overweight has not been extensively investigated in follow-up studies so far," says Postdoctoral Researcher Elina Engberg. Further research is needed to determine in more detail how much sedentary digital media use increases the risk of being overweight, and how much physical activity is needed, and at what intensity, to ward off such a risk. In this study, the amount of physical activity and use of digital media was reported by the children themselves, and the level of their activity was not surveyed, so there is a need for further studies. "A good rule of thumb is to adhere to the physical activity guidelines for children and adolescents, according to which school-aged children and adolescents should be physically active in a versatile, brisk and strenuous manner for at least 60 minutes a day in a way that suits the individual, considering their age," says Engberg. In addition, excessive and extended sedentary activity should be avoided.

Red and processed meat linked to increased risk of heart disease, study shows Oxford University, July 21, 2021 Globally, coronary heart diseases (caused by narrowed arteries that supply the heart with blood) claim nearly nine million lives each year1, the largest of any disease, and present a huge burden to health systems. Until now, it has been unclear whether eating meat increases the risk of heart disease, and if this varies for different kinds of meat. Researchers at the University of Oxford's Nuffield Department of Population Health have conducted the largest systematic review of the prospective evidence to date, including thirteen cohort studies involving over 1.4 million people. The study participants completed detailed dietary assessments, and their health was tracked for up to 30 years. The results are published today in Critical Reviews in Food Science and Nutrition. Overall, the evidence from the analysis indicated that: Each 50 g/day higher intake of processed meat (e.g. bacon, ham, and sausages) increased the risk of coronary heart disease by 18%. Each 50 g/day higher intake of unprocessed red meat (such as beef, lamb and pork) increased the risk of coronary heart disease by 9%. There was no clear link between eating poultry (such as chicken and turkey) and an increased risk of coronary heart disease. The findings may be because of the high content of saturated fat in red meat, and of sodium (salt) in processed meat. High intakes of saturated fat increase levels of harmful low-density lipoprotein (LDL) cholesterol, whilst excess salt consumption raises blood pressure. Both LDL cholesterol and high blood pressure are well-established risk factors for coronary heart disease. Previous work from the same research team has also indicated that even moderate intakes of red and processed meat are associated with increased risk of bowel cancer2. Dr. Keren Papier (Nuffield Department of Population Health), co-lead author of the study, said: "Red and processed meat have been consistently linked with bowel cancer and our findings suggest an additional role in heart disease. Therefore, current recommendations to limit red and processed meat consumption may also assist with the prevention of coronary heart disease." Dr. Anika Knüppel, from the Nuffield Department of Population Health and the other co-lead author of the study, added: "We know that meat production is a major contributor to greenhouse gas emissions and we need to reduce meat production and thereby consumption to benefit the environment. Our study shows that a reduction in red and processed meat intake would bring personal health benefits too." Currently in the UK, about 10 in 100 people would be expected to eventually die from coronary heart disease. Based on the findings from the present study and current red and processed meat intakes in the UK,4 if all these 100 people reduced their unprocessed red meat intake by three-quarters (for example from four times a week to one time a week), or if they stopped consuming processed meat altogether, deaths from coronary heart disease would decrease from 10 in 100 down to 9 in 100. The studies involved in this analysis were mostly based on white adults living in Europe or the U.S.. The research team say more data are needed to examine these associations in other populations, including East Asia and Africa.   C is for Vitamin C -- a key ingredient for immune cell function Harnessing the combined power of Vitamin C and TET proteins may give scientists a leg up in treating autoimmune diseases   La Jolla Institute for Immunology and Emory University, July 22, 2021 You can't make a banana split without bananas. And you can't generate stable regulatory T cells without Vitamin C or enzymes called TET proteins, it appears.  Regulatory T cells (Tregs) help control inflammation and autoimmunity in the body. Tregs are so important, in fact, that scientists are working to generate stable induced Tregs (iTregs) in vitro for use as treatments for autoimmune diseases as well as rejection to transplanted organs. Unfortunately, it has proven difficult to find the right molecular ingredients to induce stable iTregs. Now scientists at La Jolla Institute for Immunology and Emory University School of Medicine report that Vitamin C and TET proteins can work together to give Tregs their life-saving power.  "Vitamin C can be used to stabilize iTregs generated in vitro," says LJI Instructor Xiaojing Yue, Ph.D., who served as co-first author for the EMBO Reports study. "We hope that these kinds of induced Tregs can be used in the future for treatment of autoimmune diseases and organ transplantation." The recent study, led by LJI Professor Anjana Rao, Ph.D., and Emory Instructor Benjamin G Barwick, Ph.D., builds on the previous discovery that Vitamin C can enhance the enzymatic activity of TET proteins and prompt the generation of stable iTregs under lab conditions. This finding was encouraging, but the scientists did not want to work toward new autoimmune therapies without first analyzing the gene expression patterns and other key epigenetic features of the induced Tregs.  "We wanted to study the entire system at a whole genome level using next generation sequencing technology to better understand the molecular features of these cells," says Yue. Study co-first author Daniela Samaniego-Castruita, a graduate student at LJI, spearheaded the analysis of gene expression and epigenetic changes in the iTregs. A major type of epigenetic modification involves the DNA itself through the addition or removal of molecules called methyl groups from cytosines, one of the four DNA bases. The methyl groups can be further oxidized by TET enzymes. All of these interactions can eventually change how cells "read" the DNA code.  Another type of epigenetic change involves the alteration of DNA accessibility: whether DNA is loosely or tightly coiled. As the DNA coils unwind, regulatory regions become exposed which subsequently influence gene expression. In their analysis, the researchers found TET proteins are absolutely required for maintaining the gene expression and epigenetic features that make Tregs as what they are; and adding Vitamin C led to iTregs with similar similar gene expression and epigenetic features as normal "wild type" Tregs found in the body. The study also reveals an intriguing connection between TET enzymatic activity, Vitamin C and IL-2/STAT5 signaling. "In mice that are deficient for components of IL-2/STAT5 signaling, such as IL-2, IL-2 receptors or STAT5, the Tregs cannot develop properly or they can have impaired function," Yue says. The researchers demonstrate that on one hand, TET-deficiency in Treg cells leads to impaired IL-2/STAT5 signaling; on the other hand, Vitamin C confers iTregs enhanced IL-2/STAT5 signaling by increasing the expression level of IL-2 receptor and the functional form of STAT5, and STAT5 binding to essential regions in the genome, rendering these cells survive better in tough environments with low IL-2 supplementation. "We are looking for more small molecules to stabilize TET activity and generate induced Tregs that are even more stable," says Yue. "These induced Tregs could eventually be used to treat patients." "This research gives us a new way to think about treating autoimmune diseases," says Samaniego-Castruita.       Resveratrol ameliorates high-fat-diet-induced abnormalities in liver glucose metabolism in mice via the AMPK pathway Hebei Medical Institute (China), July 19, 2021 A new study on high fat diet is now available. According to news originating from the Department of Internal Medicine by NewsRx correspondents, research stated, “Diabetes mellitus is highly prevalent worldwide.” Our news reporters obtained a quote from the research from Department of Internal Medicine: “High-fat-diet (HFD) consumption can lead to liver fat accumulation, impair hepatic glycometabolism, and cause insulin resistance and the development of diabetes. Resveratrol has been shown to improve the blood glucose concentration of diabetic mice, but its effect on the abnormal hepatic glycometabolism induced by HFD-feeding and the mechanism involved are unknown. In this study, we determined the effects of resveratrol on the insulin resistance of high-fat-diet-fed mice and a hepatocyte model by measuring serum biochemical indexes, key indicators of glycometabolism, glucose uptake, and glycogen synthesis in hepatocytes. We found that resveratrol treatment significantly ameliorated the HFD-induced abnormalities in glucose metabolism in mice, increased glucose absorption and glycogen synthesis, downregulated protein phosphatase 2A (PP2A) and activated Ca2+/CaM-dependent protein kinase kinase b (CaMKKb), and increased the phosphorylation of AMP-activated protein kinase (AMPK). In insulin-resistant HepG2 cells, the administration of a PP2A activator or CaMKKb inhibitor attenuated the effects of resveratrol, but the administration of an AMPK inhibitor abolished the effects of resveratrol. Resveratrol significantly ameliorates abnormalities in glycometabolism induced by HFD-feeding and increases glucose uptake and glycogen synthesis in hepatocytes.” According to the news editors, the research concluded: “These effects are mediated through the activation of AMPK by PP2A and CaMKKb.”     Hundreds of chemicals, many in consumer products, could increase breast cancer risk List includes potential carcinogens that act by stimulating production of hormones that fuel breast tumors Silent Spring Institute, July 22, 2021 Every day, people are exposed to a variety of synthetic chemicals through the products they use or the food they eat. For many of these chemicals, the health effects are unknown. Now a new study shows that several hundred common chemicals, including pesticides, ingredients in consumer products, food additives, and drinking water contaminants, could increase the risk of breast cancer by causing cells in breast tissue to produce more of the hormones estrogen or progesterone. "The connection between estrogen and progesterone and breast cancer is well established," says co-author Ruthann Rudel, a toxicologist and research director at Silent Spring Institute. "So, we should be extremely cautious about chemicals in products that increase levels of these hormones in the body." For instance, in 2002, when the Women's Health Initiative study found combination hormone replacement therapy to be associated with an increased risk of breast cancer, women stopped taking the drugs and incidence rates went down. "Not surprisingly, one of the most common therapies for treating breast cancer is a class of drugs called aromatase inhibitors that lower levels of estrogen in the body, depriving breast cancer cells of the hormones they need to grow," adds Rudel. To identify these chemical risk factors, Rudel and Silent Spring scientist Bethsaida Cardona combed through data on more than 2000 chemicals generated by the U.S. Environmental Protection Agency (EPA)'s ToxCast program. The goal of ToxCast is to improve the ability of scientists to predict whether a chemical will be harmful or not. The program uses automated chemical screening technologies to expose living cells to chemicals and then examine the different biological changes they cause. Reporting in the journal Environmental Health Perspectives, Rudel and Cardona identified 296 chemicals that were found to increase estradiol (a form of estrogen) or progesterone in cells in the laboratory. Seventy-one chemicals were found to increase levels of both hormones. The chemicals included ingredients in personal care products such as hair dye, chemical flame retardants in building materials and furnishings, and a number of pesticides. The researchers don't yet know how these chemicals are causing cells to produce more hormones. It could be the chemicals are acting as aromatase activators, for instance, which would lead to higher levels of estrogen, says Cardona. "What we do know is that women are exposed to multiple chemicals from multiple sources on a daily basis, and that these exposures add up." The Silent Spring researchers hope this study will be a wakeup call for regulators and manufacturers in how they test chemicals for safety. For instance, current safety tests in animals fail to look at changes in hormone levels in the animal's mammary glands in response to a chemical exposure. And, although high throughput testing in cells has been used to identify chemicals that activate the estrogen receptor, mimicking estrogen, the testing has not been used to identify chemicals that increase estrogen or progesterone synthesis. "This study shows that a number of chemicals currently in use have the ability to manipulate hormones known to adversely affect breast cancer risk," says Dr. Sue Fenton, associate editor for the study and an expert in mammary gland development at the National Institute of Environmental Health Sciences. "Especially concerning is the number of chemicals that alter progesterone, the potential bad actor in hormone replacement therapy. Chemicals that elevate progesterone levels in the breast should be minimized." The researchers outlined a number of recommendations in their study for improving chemical safety testing to help identify potential breast carcinogens before they end up in products, and suggest finding ways to reduce people's exposures, particularly during critical periods of development, such as during puberty or pregnancy when the breast undergoes important changes. The project is part of Silent Spring Institute's Safer Chemicals Program which is developing new cost-effective ways of screening chemicals for their effects on the breast. Knowledge generated by this effort will help government agencies regulate chemicals more effectively and assist companies in developing safer products.     Antioxidant activity of limonene counteracts neurotoxicity triggered by amyloid beta 1-42 oligomers in cortical neurons University of Naples (Italy), July 19, 2021 According to news reporting from Naples, Italy, by NewsRx journalists, research stated, “Many natural-derived compounds, including the essential oils from plants, are investigated to find new potential protective agents in several neurodegenerative disorders such as Alzheimer's disease (AD).” The news editors obtained a quote from the research from School of Medicine: “In the present study, we tested the neuroprotective effect of limonene, one of the main components of the genus * * Citrus* * , against the neurotoxicity elicited by Ab [ [1-42] ] oligomers, currently considered a triggering factor in AD. To this aim, we assessed the acetylcholinesterase activity by Ellman's colorimetric method, the mitochondrial dehydrogenase activity by MTT assay, the nuclear morphology by Hoechst 33258, the generation of reactive oxygen species (ROS) by DCFH-DA fluorescent dye, and the electrophysiological activity of K [ [V] ] 3.4 potassium channel subunits by patch-clamp electrophysiology. Interestingly, the monoterpene limonene showed a specific activity against acetylcholinesterase with an IC [ [50] ] almost comparable to that of galantamine, used as positive control. Moreover, at the concentration of 10 g/mL, limonene counteracted the increase of ROS production triggered by Ab [ [1-42] ] oligomers, thus preventing the upregulation of K [ [V] ] 3.4 activity. This, in turn, prevented cell death in primary cortical neurons, showing an interesting neuroprotective profile against Ab [ [1-42] ] -induced toxicity.” According to the news editors, the research concluded: “Collectively, the present results showed that the antioxidant properties of the main component of the genus * * Citrus* * , limonene, may be useful to prevent neuronal suffering induced by Ab [ [1-42] ] oligomers preventing the hyperactivity of K [ [V] ] 3.4.”     Meditation And Yoga Change Your DNA To Reverse Effects Of Stress, Study Shows Coventry University (UK), July 22, 2021 Many people participate in practices such as meditation and yoga because they help us relax. At least those are the immediate effects we feel. But much more is happening on a molecular level, reveal researchers out of Coventry University in England. Published in the journal Frontiers in Immunology, this new research examined 18 studies on mind-body interventions (MBIs). These include practices such as mindfulness meditation and yoga. Comprehensively, these studies encompassed 846 participants over 11 years. The new analysis reveals that MBIs result in molecular changes in the human body. Furthermore, researchers claim that these changes are beneficial to our mental and physical health. Body's Response to Stress Causes Damage To elaborate, consider the effect that stress has on the body. When we are under stress, the body increases the production of proteins that cause cell inflammation. This is the natural effect of the body's fight-or-flight response. It is widely believed that inflammation in the body leads to numerous illnesses, including cancer. Moreover, scientists also deduct that a persistent inflammation is more likely to cause psychiatric problems. Unfortunately, many people suffer from persistent stress, therefore they suffer from pro-inflammatory gene expression. But there is good news! According to this new analysis out of Coventry, people that practice MBIs such as meditation and yoga can reverse pro-inflammatory gene expression. This results in a reduced risk of inflammation-related diseases and mental conditions. Lead investigator Ivana Buric from Coventry University's Centre for Psychology, Behaviour and Achievement stated: Millions of people around the world already enjoy the health benefits of mind-body interventions like yoga or meditation, but what they perhaps don't realise is that these benefits begin at a molecular level and can change the way our genetic code goes about its business. These activities are leaving what we call a molecular signature in our cells, which reverses the effect that stress or anxiety would have on the body by changing how our genes are expressed. Put simply, MBIs cause the brain to steer our DNA processes along a path which improves our wellbeing. More needs to be done to understand these effects in greater depth, for example how they compare with other healthy interventions like exercise or nutrition. But this is an important foundation to build on to help future researchers explore the benefits of increasingly popular mind-body activities.               Large-scale study finds greater sedentary hours increases risk of obstructive sleep apnea Study finds that maintaining an active lifestyle can reduce the risk of OSA, encourages physicians to recommend exercise-based interventions for those at risk Brigham and Women's Hospital, July 22, 2021 A new study by investigators from Brigham and Women's Hospital examined the relationship between active lifestyles and the risk of obstructive sleep apnea (OSA). The study followed around 130,000 men and women in the United States over a follow-up period of 10-to-18 years and found that higher levels of physical activity and lower levels of sedentary behavior were associated with a lower risk of OSA. Their results are published in the European Respiratory Journal.  "In our study, higher levels of physical activity and fewer hours of TV watching, and sitting either at work or away from home were associated with lower OSA incidence after accounting for potential confounders," said Tianyi Huang, MSc, ScD, an Associate Epidemiologist at the Brigham. "Our results suggest that promoting an active lifestyle may have substantial benefits for both prevention and treatment of OSA."  OSA is a type of sleep apnea in which some muscles relax during sleep, causing an airflow blockage. Severe OSA increases the risk of various heart issues, including abnormal heart rhythms and heart failure.  Using the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII) and Health Professionals Follow-Up Study (HPFS), the research team used statistical modeling to compare physical activity and sedentary hours with diagnoses of OSA. Both moderate and vigorous physical activity were examined separately and both were strongly correlated with lower risk of OSA, showing no appreciable differences in the intensity of activity. Moreover, stronger associations were found for women, adults over the age of 65 and those with a BMI greater than or equal to 25 kg/m2.  "Most prior observational studies on the associations of physical activity and sedentary behavior with OSA were cross-sectional, with incomplete exposure assessment and inadequate control for confounding," said Huang. "This is the first prospective study that simultaneously evaluates physical activity and sedentary behavior in relation to OSA risk."  This study also differs from others because of its large sample size and detailed assessment pf physical activity and sedentary behaviors. The research team was able to take many associated factors into account, making the findings more credible.  The authors note that all collected data, both of OSA diagnosis and physical activity or sedentary behavior, were self-reported. While all study participants were health professionals, mild OSA is often difficult to detect and can remain clinically unrecognized. Furthermore, only recreational physical activity was taken into consideration, leaving out any physical activity in occupational settings. Sedentary behavior was only counted as sitting while watching TV and sitting away from home or at work.  According to Huang, the next research steps would be to collect data using actigraphy, home sleep apnea tests and polysomnography, rather than self-reports.  In light of the findings, investigators encourage physicians to highlight the benefits of physical activity to lower OSA risk.  "We found that physical activity and sedentary behavior are independently associated with OSA risk," said Huang. "That is, for people who spend long hours sitting every day, increasing physical activity in their leisure time can equally lower OSA risk. Similarly, for those who are not able to participate in a lot of physical activity due to physical restrictions, reducing sedentary hours by standing or doing some mild activities could also lower OSA risk. However, those who can lower sedentary time and increase physical activity would have the lowest risk."

Being a leader in a Vuca (volatility, uncertainty, complexity, and ambiguity) world is not easy and according to Susanne Marell, requires listening. And listening takes different forms. Listening to the market and customer trends, listening to my team needs, listening to individual needs and listening to feedback from my team, not to mention the questions that arise.   How can we listen in a way that gives us energy to think strategically and create success in a company, even through challenging mergers and acquisitions.   Susanne Marell is CEO of Hill+Knowlton Strategies in Germany. Before joining H+K she was Managing Director at JP KOM and prior to that she served as CEO of Edelman for six years, overseeing the acquisition and merger with ergo Kommunikation.   She started her career as a consultant with the agency Kohtes & Klewes (now Ketchum). In the following years, Marell worked for companies such as Schering, Hoechst and Aventis CropScience. As Head of Communications and Market Services, her responsibilities included strategic communications support for merger and acquisition activities. In 2000, she moved to the chemical company Cognis and, as Vice President Corporate Communications, took over the management of worldwide corporate and sustainability communications. Following the acquisition of Cognis by BASF in 2010, Susanne was responsible for global brand management as Vice President Corporate Brand Management at BASF in Ludwigshafen.   Susanne is a certified systemic consultant and change expert. She has many years of international experience in communications, marketing and sustainability, both on the corporate and agency side. In addition, she is a co-founder of the German network of "Global Women in PR" and has built up the initiative "Next Gen Leadership" as a member of the extended board.   In this episode, Susanne Marell shares how continuous feedback is needed to be a great leader; it helps you listen to make a more objective assessment while keeping you on the pulse of the organization, what your team needs and how you can move together towards a common goal with market trends top of mind.   She points out that psychological safety, where people are provided a safe space to be heard without fear of consequences, ensures open and honest feedback.    She also highlights the importance of leaders understanding market and customer trends first when leading teams. She calls this an outside-in approach so that you can understand the bigger picture around what you want to achieve by listening to all the stakeholders.   "A leader needs feedback to be a good leader."  - Susanne Marell Listen IN Notes:   01:10 - The first time she experienced being a communication practitioner and becoming a good leader 02:40 - Only by listening in a new business model will you be able to understand the context and how things play together 05:14 - How listening supported her leadership role as being part of an integration team 9:25 - To better understand what is behind any criticism and feedback: You must learn how to frame things, dig into the details, and learn the context of what you put in your story line,. If they [colleagues] are positive towards you, they will  stress test your vision. 13:57 - Feedback being the highest value for a leader 16:46 - Providing psychological safety in leadership sessions 19:13 - Going in front of people [employees and investors] even in uncertain times and you don't know all the answers 21:28 - What it means to be a leader in a VUCA world 23:13 - Focusing your team on the outside in 24:56 - Giving a Northstar is just as important as giving people the 100 criteria 27:08 - What does being agile in today's world mean? 37:50 - He who poses the questions is the one who leads 43:28 - One listening style: Posing questions on a 360 degree angle 45:23 - Having a full scope of questions beyond Zoom meetings avoids risks in losing so  many things 47:48 - Finding the right way to be on the pulse of your organization, of your teams, and of  your decisions 49:43 - Creative ways you can do where voices are heard outside of work environment 51:38 - Is listening agreeing to what people say? Key Takeaways:    "In all of these projects, where I was part of integration teams, I simply had to listen very well first to give a good recommendation about how we could integrate teams. But also to develop the vision of why these companies work together and put this vision in a storyline, which would be understood by all people globally." - Susanne Marell   "Feedback is something which is of the highest value for a leader. If I'm getting feedback, this helps me to develop, but it also helps me to give a better analysis of where my team stands where my plans stand." - Susanne Marell   "The positive part of listening is you get feedback." - Susanne Marell   "Leading in uncertain times simply means that you have to navigate your team through those times as best as possible, even if you don't always have the answers." - Susanne Marell   "It is best to tackle with trust. Because if I trust my people that they will strive for the best solutions, they will come to me for guidance, then it's easier for me to decide without having all the facts." - Susanne Marell   "Your North Star is of even bigger importance. Because if you have the direction clear where you would like to go, then at least you have a kind of decision corridor, even if you do not all have the facts and things are changing." - Susanne Marell   "When we just focus on Zoom teams and just checking where we stand with our business, we will lose so many things. Now we have a full scope of questions adjusted to the person I talked to." - Susanne Marell Connect with Susanne Marell:   LinkedIn https://www.hkstrategies.com/  Facebook Instagram Twitter   Connect with Raquel Ark: www.listeningalchemy.com Mobile: + 491732340722 contact@listeningalchemy.com LinkedIn

Treatment with Rhodiola mimics exercise to resist high-fat diet-induced muscle dysfunction Central South University (China), April 30, 2021   According to news reporting out of Changsha, People’s Republic of China, research stated, “Muscle dysfunction is a complication of high-fat diet (HFD)-induced obesity that could be prevented by exercise, but patients did not get enough therapeutic efficacy from exercise due to multiple reasons.” The news reporters obtained a quote from the research from Xiangya Hospital of Central South University: “To explore alternative or supplementary approaches to prevent or treat muscle dysfunction in individuals with obesity, we investigated the effects of Rhodiola on muscle dysfunction as exercise pills. SIRT1 might suppress atrogenes expression and improve mitochondrial quality control, which could be a therapeutic target stimulated by exercise and Rhodiola, but further mechanisms remain unclear. We verified the lipid metabolism disorders and skeletal muscle dysfunction in HFD feeding mice. Moreover, exercise and Rhodiola were used to intervene mice with a HFD. Our results showed that exercise and Rhodiola prevented muscle atrophy and dysfunction in obese mice and activating the SIRT1 pathway, while atrogenes were suppressed and mitochondrial quality control was improved. EX-527, SIRT1 inhibitor, was used to validate the essential role of SIRT1 in salidroside benefit.” According to the news editors, the research concluded: “Results of cell culture experiment showed that salidroside alleviated high palmitate-induced atrophy and mitochondrial quality control impairments, but these improvements of salidroside were inhibited by EX-527 in C2C12 myotubes. Overall, Rhodiola mimics exercise that activates SIRT1 signaling leading to improvement of HFD-induced muscle dysfunction.”     Prenatal exposure to pesticides increases the risk of obesity in adolescence First study to analyse the long-term effects of persistent organic pollutants on cardiometabolic risk in adolescents Barcelona Institute for Global Health (Spain), May 3, 2021 Exposure before birth to persistent organic pollutants (POPs)-- organochlorine pesticides, industrial chemicals, etc.--may increase the risk in adolescence of metabolic disorders, such as obesity and high blood pressure. This was the main conclusion of a study by the Barcelona Institute for Global Health (ISGlobal), a research centre supported by the "la Caixa" Foundation. The study was based on data from nearly 400 children living in Menorca, who were followed from before birth until they reached 18 years of age.  POPs are toxic, degradation-resistant chemicals that persist in the environment. Examples of such compounds are pesticides and organochlorine insecticides (DDT, etc.). POPs have adverse effects on both human health and the environment and their use is regulated globally. Prenatal exposure to these substances has been associated with cardiometabolic risk factors in childhood, but there were previously no studies assessing whether such associations continue into adolescence, a developmental stage characterised by significant changes in the endocrine system and rapid increases in body mass. The aim of this investigation, carried out within the framework of the INMA Project-Environment and Childhood, was to study the associations between prenatal exposure to POPs and body mass index (BMI) as well as other markers of cardiovascular risk in adolescence. Data from 379 children in Menorca was analysed. POP levels were measured in umbilical cord blood samples and the children were then seen periodically between the ages of 4 and 18 years. At these visits, BMI, body fat percentage and blood pressure were recorded as they grew. When the child reached 14 years of age, the scientists measured blood biomarkers of cardiometabolic risk (cholesterol, triglycerides, glucose, etc.). The results of this study, published in the journal Environment International, suggest an association between prenatal POP exposure and a higher BMI in adolescence, particularly in the case of the fungicide hexachlorobenzene (HCB) and the insecticide compound dichloro-diphenyl-trichloroethane (DDT).  Exposure to these two organochlorides--HCB and DDT¬--was also associated with higher blood pressure in childhood and adolescence and increased cardiometabolic risk at 14 years of age.  ISGlobal researcher Núria Güil-Oumrait, the first author of the study, explains that "this is the first longitudinal study to analyse the relationship between persistent organic pollutants and cardiometabolic risk throughout childhood and adolescence. Our findings show that the association between these substances and infant BMI does persist into adolescence and that prenatal exposures are associated with the main risk factors for metabolic syndrome in adults, a condition that today affects one in four people worldwide. With respect to the mechanisms that might explain this association, Güil-Oumrait points out that "it is thought that POPs may interact with hormone receptors or with the generation of free radicals, and the chief problem is that these pollutants accumulate in the fatty tissues of living organisms, where they can persist for years, even decades".  Martine Vrijheid, study coordinator and head of the Childhood and Environment Programme at ISGlobal, highlights the fact that "some of these substances could be considered endocrine disruptors, that is, chemicals that interfere with hormonal regulation". In her view "more studies are needed in this field, especially focussing on childhood and adolescence, which are critical developmental stages characterised by particular vulnerability".     One cup of leafy green vegetables a day lowers risk of heart disease Research has found that by eating just one cup of nitrate-rich vegetables each day people can significantly reduce their risk of heart disease. Edith Cowan University (Australia), May 4, 2021 New Edith Cowan University (ECU) research has found that by eating just one cup of nitrate-rich vegetables each day people can significantly reduce their risk of heart disease. The study investigated whether people who regularly ate higher quantities of nitrate-rich vegetables, such as leafy greens and beetroot, had lower blood pressure, and it also examined whether these same people were less likely to be diagnosed with heart disease many years later. Cardiovascular diseases are the number one cause of death globally, taking around 17.9 million lives each year. Researchers examined data from over 50,000 people residing in Denmark taking part in the Danish Diet, Cancer, and Health Study over a 23-year period. They found that people who consumed the most nitrate-rich vegetables had about a 2.5 mmHg lower systolic blood pressure and between 12 to 26 percent lower risk of heart disease. Lead researcher Dr Catherine Bondonno from ECU's Institute for Nutrition Research said identifying diets to prevent heart disease was a priority. "Our results have shown that by simply eating one cup of raw (or half a cup of cooked) nitrate-rich vegetables each day, people may be able to significantly reduce their risk of cardiovascular disease," Dr Bondonno said. "The greatest reduction in risk was for peripheral artery disease (26 percent), a type of heart disease characterised by the narrowing of blood vessels of the legs, however we also found people had a lower risk of heart attacks, strokes and heart failure."  Forget the supplements The study found that the optimum amount of nitrate-rich vegetables was one cup a day and eating more than that didn't seem to give any additional benefits. "People don't need to be taking supplements to boost their nitrate levels because the study showed that one cup of leafy green vegetables each day is enough to reap the benefits for heart disease," Dr Bondonno said. "We did not see further benefits in people who ate higher levels of nitrate rich vegetables." Smoothies are ok Dr Bondonno said hacks such as including a cup of spinach in a banana or berry smoothie might be an easy way to top up our daily leafy greens. "Blending leafy greens is fine, but don't juice them. Juicing vegetables removes the pulp and fibre," Dr Bondonno said. The paper "Vegetable nitrate intake, blood pressure and incident cardiovascular disease: Danish Diet, Cancer, and Health Study" is published in the European Journal of Epidemiology. It is a collaboration between Edith Cowan University, the Danish Cancer Society and The University of Western Australia. The research adds to growing evidence linking vegetables generally and leafy greens specifically with improved cardiovascular health and muscle strength. This evidence includes two recent ECU studies exploring cruciferous vegetables and blood vessel health and green leafy vegetables and muscle strength.     Mindfulness programs can boost children's mental health   University of Derby (UK), May 4, 2021 Mindfulness programs can improve the mental health of school-age children and help them to feel more optimistic, according to new research from the University of Derby and Derbyshire Educational Psychology Service. More than 1,000 pupils aged between 9-12 years old across 25 schools in Derbyshire, received one 45-minute mindfulness session per week for nine weeks during the year-long project, which involved a collaboration between Dr. William Van Gordon, Associate Professor in Contemplative Psychology at the University, and Derbyshire Educational Psychology Service. Mindfulness is an ancient meditation technique that involves focussing awareness on the present moment, as a means of fostering calm, wellbeing and insight. The weekly sessions involved activities such as practicing mindful breathing and paying attention to bodily sensations, as well as exercises intended to help cultivate attention skills and a greater awareness of emotions. The impact of the sessions, which were delivered by teachers in a traditional classroom environment, was evaluated by comparing psychological assessments that the children completed before the classes began, with assessments undertaken after the program had concluded. Part of the evaluation measured children's emotional resiliency using The Resiliency Scale for Children, while wellbeing was rated using the Stirling Children's Wellbeing Scale. Overall, the study found a significant improvement in positive emotional state, outlook and resiliency. There was also an increase in the different dimensions of resilience: optimism increased by 10%, tolerance was improved by 8% and self-efficacy, how a child feels they can cope with a situation based on the skills they have and the circumstances they face, improved by 11%. Professor Van Gordon said: "Findings from the study indicate that mindfulness delivered by school teachers can improve wellbeing and resiliency in children and young people. "This is consistent with wider evidence demonstrating the positive impact of mindfulness on school children's levels of emotional resiliency, emotional stability, wellbeing and stress. "These findings are also in line with the view that preventative interventions given at a young age can help to reduce the incidence of mental health problems in young people."   Vitamin D levels higher in exercisers Johns Hopkins University, May 01 2021  The issue of the Journal of Clinical Endocrinology & Metabolism published the finding of researchers at Johns Hopkins University of a correlation between increased physical activity and higher levels of vitamin D. Higher levels of vitamin D and exercise was also associated with a lower risk of cardiovascular disease. The study included 10,342 men and women who were free of coronary heart disease and heart failure upon enrollment in the Atherosclerosis Risk in Communities study. Physical activity levels were assessed during follow-up visits that took place over a 19.3-year period. Stored serum samples obtained at the second visit were analyzed for 25-hydroxyvitamin D3. Subjects who achieved American Heart Association recommended physical activity levels had average levels of vitamin D that were higher than those who had intermediate and poor levels of activity. Following adjustment for lifestyle and other factors, those who met the recommended levels had a 31% lower risk of being deficient in vitamin D than those with poor activity levels. Subjects in the recommended activity group with levels of vitamin D of 30 ng/mL or more had a 24% lower risk of cardiovascular disease. The association between exercise and vitamin D was stronger in subjects of European ethnicity than among African Americans. The authors noted that European-Americans as well as those who engage in exercise are likelier to be supplement users. “We did find that vitamin D supplement use was higher among those with increased physical activity,” they observed. "In our study, both failure to meet the recommended physical activity levels and having vitamin D deficiency were very common" stated coauthor Erin Michos, MD, MS, of Johns Hopkins University School of Medicine. "The bottom line is we need to encourage people to move more in the name of heart health."     One teaspoon daily of trehalose can help maintain glucose homeostasis: a double-blind, randomized controlled trial  Hayashibara Co. Ltd (Japan), April 24, 2021 Background Trehalose is a natural disaccharide that is widely distributed. A previous study has shown that daily consumption of 10 g of trehalose improves glucose tolerance in individuals with signs of metabolic syndrome. In the present study, we determined whether a lower dose (3.3 g/day) of trehalose improves glucose tolerance in healthy Japanese volunteers. Methods This was a randomized, double-blind, placebo-controlled study of healthy Japanese participants (n = 50). Each consumed 3.3 g of trehalose (n = 25) or sucrose (n = 25) daily for 78 days. Their body compositions were assessed following 0, 4, 8, and 12 weeks; and serum biochemical parameters were assayed and oral 75-g glucose tolerance tests were performed at baseline and after 12 weeks. Results There were similar changes in body composition and serum biochemistry consistent with established seasonal variations in both groups, but there were no differences in any of these parameters between the two groups. However, whereas after 12 weeks of sucrose consumption, the plasma glucose concentration 2 h after a 75-g glucose load was significantly higher than the fasting concentration, after 12 weeks of trehalose consumption the fasting and 2-h plasma glucose concentrations were similar. Furthermore, an analysis of the participants with relatively high postprandial blood glucose showed that the plasma glucose concentration 2 h after a 75-g glucose load was significantly lower in the trehalose group than in the sucrose group. Conclusions Our findings suggest that trehalose helps lower postprandial blood glucose in healthy humans with higher postprandial glucose levels within the normal range, and may therefore contribute to the prevention of pathologies that are predisposed to by postprandial hyperglycemia,, even if the daily intake of trehalose is only 3.3 g, an amount that is easily incorporated into a meal.     Coffee compound enhances autophagy to protect against cell injury Chengdu University of Traditional Chinese Medicine (China), April 30, 2021 According to news reporting originating from Sichuan, People’s Republic of China, research stated, “Autophagy serves an important role in amyloid-beta (A beta) metabolism and tau processing and clearance in Alzheimer’s disease. The progression of A beta plaque accumulation and hyperphosphorylation of tau proteins are enhanced by oxidative stress.” Our news editors obtained a quote from the research from the Chengdu University of Traditional Chinese Medicine, “A hydrogen peroxide (H2O2) injury cell model was established using SH-SY5Y cells. Cells were randomly divided into normal, H2O2 and chlorogenic acid (5-caffeoylquinic acid; CGA) groups. The influence of CGA on cell viability was evaluated using a Cell Counting Kit-8 assay and cell death was assessed using Hoechst 33342 nuclear staining. Autophagy induction and fusion of autophagic vacuoles assays were performed using monodansylcadaverine staining. Additionally, SH-SY5Y cells expressing Ad-mCherry-green fluorescent protein-LC3B were established to detect autophagic flow. LysoTracker Red staining was used to evaluate lysosome function and LysoSensor ™ Green staining assays were used to assess lysosomal acidification. The results demonstrated that CGA decreased the apoptosis rate, increased cell viability and improved cell morphology in H2O2-treated SH-SY5Y cells. Furthermore, CGA alleviated the accumulation of autophagic vacuoles, reduced the LC3BII/I ratio and decreased P62 levels, resulting in increased autophagic flux. Additionally, CGA upregulated lysosome acidity and increased the expression levels of cathepsin D. Importantly, these effects of CGA on H2O2-treated SH-SY5Y cells were mediated via the mTOR-transcription factor EB signaling pathway.” According to the news editors, the research concluded: “These results indicated that CGA protected cells against H2O2-induced oxidative damage via the upregulation of autophagosomes, which promoted autophagocytic degradation and increased autophagic flux.” This research has been peer-reviewed.

Dear community: This conversation was held in German language. Herzlich willkommen zum 2. Teil meines Gesprächs mit Barbara Liebermeister. Unser Thema: Digital Leadership - wie Führung heute funktioniert. Das erwartet euch: 00:00 - Über "Die Führungskraft als Influencer" & Team Management 09:38 - Oxytocin & Digitale Kommunikation 17:25 - Der moderne Führungsstil 21:55 - Social Media Focus Barbara Liebermeister ist Wirtschaftswissenschaftlerin sowie Gründerin und Leiterin des Instituts für Führungskultur im digitalen Zeitalter (IFIDZ) in Frankfurt. Ihre Karriere begann die heutige Managementberaterin und Keynote-Speakerin im Marketing und Vertrieb internationaler Konzerne wie Christian Dior, L‘OREAL und Hoechst. Später leitete sie Projekte für die Royal Bank of Scotland, die Deutsche Bank, Merck, Fidelity International und viele andere. Barbara Liebermeister ist Rednerin, Managementberaterin und Autorin. Sie schrieb mehrere Fachbücher und zahlreiche Fachartikel zum Themenkomplex Führung bzw. Leadership und Networking im digitalen Zeitalter. Ihr neuestes Buch „DIE FÜHRUNGSKRAFT ALS INFLUENCER“ ist ab sofort im Handel erhältlich. Hier könnt ihr es probelesen: https://bit.ly/2RJ861f Mehr zu Barbara Liebermeister

Dear community: This conversation was held in German language. Herzlich willkommen zum 1. Teil meines Gesprächs mit Barbara Liebermeister. Unser Thema: Digital Leadership - wie Führung heute funktioniert. Das erwartet euch: 00:00 - Intro 03:54 - Der Command & Control Chef 06:40 - Der moderne Chef IST Influencer 11:40 - Empathie im Team 14:15 - Teambildung im digitalen Zeitalter 22:20 - Vom Direktor zum Dirigent Barbara Liebermeister ist Wirtschaftswissenschaftlerin sowie Gründerin und Leiterin des Instituts für Führungskultur im digitalen Zeitalter (IFIDZ) in Frankfurt. Ihre Karriere begann die heutige Managementberaterin und Keynote-Speakerin im Marketing und Vertrieb internationaler Konzerne wie Christian Dior, L‘OREAL und Hoechst. Später leitete sie Projekte für die Royal Bank of Scotland, die Deutsche Bank, Merck, Fidelity International und viele andere. Barbara Liebermeister ist Rednerin, Managementberaterin und Autorin. Sie schrieb mehrere Fachbücher und zahlreiche Fachartikel zum Themenkomplex Führung bzw. Leadership und Networking im digitalen Zeitalter. Ihr neuestes Buch „DIE FÜHRUNGSKRAFT ALS INFLUENCER“ ist ab sofort im Handel erhältlich. Hier könnt ihr es probelesen: https://bit.ly/2RJ861f Mehr zu Barbara Liebermeister

„Frei zu gehorchen“, sei das Management-Prinzip gewesen, an dem sich viele westdeutsche Wirtschaftslenker orientiert haben - erklärt der Historiker Johann Chapoutot. Diese Denkweise sei auch durch eine nationalsozialistische Prägung entstanden, entscheidend dafür sei die in den 1950er Jahren gegründete „Akademie für Führungskräfte“ in Bad Harzburg gewesen. Sie wurde von mehr als 600.000 Führungskräften absolviert, die aus Firmen wie Aldi, BMW, Hoechst, Bayer, Esso, Krupp, Thyssen und Opel stammten.

Laurie Cooke is currently the president and CEO of the Healthcare Businesswomen Association (HBA), a non-profit organization dedicated to furthering the advancement and impact of women in the business of healthcare. Under her leadership, the organization has grown substantially to a community of nearly 60K and 150 companies, with a presence in 55 locations across the US, Canada and Europe and online communities starting in Latin America and Asia Pacific.  Laurie has been recognized as Mentor of the Year by the American Society of Association Executives, twice honored as 100 Most Inspiring People in the Life Sciences by PharmaVOICE, and Healthcare Champion by National Association of Female Executives. Laurie's career spans global roles across several industries and continents holding executive roles on the Project Management Institute's (PMI) executive management team; international teams in process improvement, team effectiveness and project management at Hoechst, Hoechst-Roussel, Hoechst Marion Roussel, and Aventis Pharmaceuticals Inc; and hospital pharmacist roles in Seattle, WA. In this episode, we discuss: ·     How the focus on female leadership shifted from readying women to trying to tackle the systematic issues that kept women off the corporate ladder. ·     Helping overall company performance by teaching men to not be afraid of the power shift to a more diverse team. ·     Why ignoring the lack of female representation in the business of healthcare will cause it to stall out and fail in the future. ·     How to embrace a full model of leadership- and not place it on gender. I hope you will find this episode as exciting and informative as I have. Please let me know your thoughts!   Connect with Laurie Cooke LinkedIn: https://www.linkedin.com/in/lauriecooke/ Twitter: https://twitter.com/lcooke9 Facebook: https://www.facebook.com/laurie.cooke.HBA Instagram: https://www.instagram.com/lcooke9/   Connect with Dr. Sharon Melnick Website: https://www.sharonmelnick.com/ LinkedIn: https://www.linkedin.com/in/sharonmelnick/ Instagram: https://www.instagram.com/drsharonmelnick/ Learn more about your ad choices. Visit megaphone.fm/adchoices

In this episode of the Epigenetics Podcast, we caught up with Margaret (“Peggy”) Goodell from Baylor College of Medicine in Houston, Texas to talk about her work on the epigenetic regulation of stem cell self-renewal and differentiation. Dr. Margret Goodell's laboratory focuses on how differentiation and self-renewal is regulated in hematopoietic stem cells (HSC). In the early stages of her research career, however, Dr. Goodell was able to develop a new method to purify stem cells. This method was based on the characteristic of stem cells to pump out the Hoechst dye that was used for the purification. In recent years, the focus of the lab has been to identify how HSCs decide whether to self-renew or differentiate. To get an answer to this question, the lab has performed genome-wide screens to find differentially expressed genes during the decision process. By doing that, they recently found that the DNA methyltransferase 3A (DNMT3A) was highly and specifically expressed in HSCs and that it is required for differentiation. When DNMT3A was knocked out in HSCs, the cell population expanded dramatically and the ability to differentiate was impaired. This finding led to further experiments in this area and to the discovery of so-called DNA methylation canyons in the genome, which are large regions of very low DNA methylation that harbor highly conserved regulator genes. In this episode we discuss how Dr. Peggy Goodell described a new approach to isolate hematopoietic stem cells even though she was not looking for that, how she discovered DNMT3A as an important factor in stem cell decision making, and how she entered and approached new fields of research along the path of her research career.    References M. A. Goodell, K. Brose, … R. C. Mulligan (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo (The Journal of Experimental Medicine) DOI: 10.1084/jem.183.4.1797 Shannon McKinney-Freeman, Margaret A. Goodell (2004) Circulating hematopoietic stem cells do not efficiently home to bone marrow during homeostasis (Experimental Hematology) DOI: 10.1016/j.exphem.2004.06.010 Stuart M. Chambers, Chad A. Shaw, … Margaret A. Goodell (2007) Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation (PLoS biology) DOI: 10.1371/journal.pbio.0050201 Grant A. Challen, Deqiang Sun, … Margaret A. Goodell (2011) Dnmt3a is essential for hematopoietic stem cell differentiation (Nature Genetics) DOI: 10.1038/ng.1009   Related Episodes Epigenetic Reprogramming During Mammalian Development (Wolf Reik) Effects of DNA Methylation on Chromatin Structure and Transcription (Dirk Schübeler) CpG Islands, DNA Methylation, and Disease (Sir Adrian Bird)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

Am 2. Dezember 1925 wurde die "Interessengemeinschaft Farbenindustrie AG", kurz IG Farben, gegründet. Acht deutsche Chemie-Unternehmen, darunter Industrie-Riesen wie Bayer, BASF und Hoechst, schlossen sich damals zu einem Chemie-Giganten zusammen.

Auf der einen Seite stand die "Interessengemeinschaft Farbenindustrie AG" für innovative Forschung und großen wirtschaftlichen Erfolg. Auf der anderen Seite ist das ehemals größte Chemieunternehmen der Welt aber auch untrennbar mit den Verbrechen der Nationalsozialisten verbunden. Im Dezember 1925 schlossen sich acht deutsche Chemie-Unternehmen zur IG Farben zusammen. Unter ihnen Industrie-Riesen wie Bayer, BASF und Hoechst. Autorin: Martina Meißner

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.11.089144v1?rss=1 Authors: Antonovaite, N., Hulshof, L. A., Hol, E. M., Wadman, W. J., Iannuzzi, D. Abstract: There is growing evidence that mechanical factors affect brain functioning. However, brain components responsible for regulating the physiological mechanical environment and causing mechanical alterations during maturation are not completely understood. To determine the relationship between structure and stiffness of the brain tissue, we performed high resolution viscoelastic mapping by dynamic indentation of hippocampus and cerebellum of juvenile brain, and quantified relative area covered by immunohistochemical staining of NeuN (neurons), GFAP (astrocytes), Hoechst (nuclei), MBP (myelin), NN18 (axons) of juvenile and adult mouse brain slices. When compared the mechanical properties of juvenile mouse brain slices with previously obtained data on adult slices, the latter was ~20-150% stiffer, which correlates with an increase in the relative area covered by astrocytes. Heterogeneity within the slice, in terms of storage modulus, correlates negatively with the relative area of nuclei and neurons, as well as myelin and axons, while the relative area of astrocytes correlates positively. Several linear regression models are suggested to predict the mechanical properties of the brain tissue based on immunohistochemical stainings. Copy rights belong to original authors. Visit the link for more info

Today, we sit down with Daniel Hoechst, a Salesforce Architect at Instructure, to talk about his experiences on the platform, including how he got started and how an MBA has factored into his approach. Plus, we talk about some of his latest projects like the Limits Monitor, an app for monitoring Salesforce org limits and Test Factory, a utility that can be used in unit tests to create test data.   Show Highlights: How being an MBA has factored into his approach to Salesforce The importance of watching for edge cases that can break limits Pitfalls that developers get into that can cause troubles for orgs Limits Monitor: an application that helps you monitor limits and then send out warnings  Test Factory: A data factory based on an older test factory project called SmartFactory    Resources: Daniel on Twitter Daniel on LinkedIn Daniel on Github Daniel's Limit Monitor Daniel's Test Factory Snowforce   Shout out: Matthew Botos   *** EPISODE CREDITS: If you like this podcast and are thinking of creating your own, consider talking to my producer, Danny Ozment. He helps thought leaders, influencers, executives, HR professionals, recruiters, lawyers, realtors, bloggers, coaches, and authors create, launch, and produce podcasts that grow their business and impact the world. Find out more at https://emeraldcitypro.com   

Gudrun unterhält sich in dieser Folge mit Lennart Hilbert, dem Leiter des Hilbert Labs am KIT. Das Labor ist Teil des Instituts für Toxikologie und Genetik (ITG), einem multidisziplinären Zentrum für biologische und chemische Forschung am KIT. Lennart Hilbert ist außerdem Juniorprofessor für Systembiologie/Bioinformatik am Zoologischen Institut des KIT. Das Thema von Lennarts Gruppe ist Computational Architectures in the Cell Nucleus. Das kann man auf zwei unterschiedliche Arten interpretieren. Einerseits untersucht Lennarts Gruppe den räumlichen Aufbau des Zellkerns mit Hilfe von Computern. Es heißt aber auch dass man aufgrund der dabei gewonnenen Erkenntnisse als Fernziel Datenverarbeitung mit Hilfe des Zellkernes als Informationsspeicher ermöglichen will. Gudrun und Lennart haben sich im Rahmen eines Treffens des KIT-Zentrums MathSEE kennengelernt, das im letzten Gespräch vorgestellt wurde. Mit der Hilfe von Super Auflösungs Mikroskopie schauen Lennart und seine Gruppe in das Innere von Zellkernen und sehen dabei dreidimensionale Bilder. Diese Bilder gleichen sie mit den Ergebnissen von den bisher standardmäßig durchgeführten Sequenzierexperimenten von Molekularbiologen ab. "Sehen" erfolgt mit empfindlichen Digitalkameras, deren Bilder geeignet gefiltert werden. Dabei ist eine einschränkende Randbedingung, dass die betrachteten Samples gegen Licht empfindlich sind, aber Licht für die visuelle Darstellung unabdingbar nötig ist - je kleiner die Details, desto mehr Licht. Man kann sich unschwer vorstellen, dass zur Bearbeitung diese Art von Fragen Informatik, Physik, Biologie und Mathematik nötig sind. Damit sich im Rahmen der Zusammenarbeit alle einbringen können, ist es hilfreich, wenn die Methoden einfach und die Ergebnisse visuell unmittelbar verständlich sind. Eine Grundannahme ist, dass die räumliche Organisation im Zellkern den Informationsflüssen aus der DNA-Sequenz entspricht. Die treibende Frage ist: Wie funktioniert Gensteuerung? Der betrachtete Regelkreis ist, dass die DNA als Bibliothek funktioniert. Aus einem Teil wird eine RNA-Kopie erstellt, sodass bestimmte Proteine hergestellt werden können. Diese Eiweiße aber steuern anschließend, welche Teile der DNA als nächstes gelesen werden (das schließt den Regelkreis). In der Systembiologie untersucht man dies bisher in Form von Differentialgleichungssystemen auf einer Metaebene. Wie das aber passiert ist aber noch relativ unklar. Die Hoffnung ist: Neues Sehen hilft hier, neues zu lernen und hierfür ist neueste Technik hilfreich. Die Molekulare Ebene ist der Teil der Biologie, wo im Moment am meisten Neues passiert. Lennart hat in Bremen Physik studiert und anschließend an der McGill University in Montréal in Physiologie promoviert. Hier hat er zum ersten Mal zwischen Theorie und Experiment in zwei Gruppen gleichzeitig gearbeitet. In Dresden am Zentrum für Systembiologie (Max Planck Institut für Molekulare Zellbiolgie und Genetik und Max Planck Institut für die Physik komplexer Systeme) konnte er als Postdoc weiterhin interdisziplinär arbeiten. Seit 2018 ist er am KIT tätig. Lennart und seine Gruppe arbeiten mit Zebrafischen, Bakterienstämmen, Zeitreihenanalyse und anderen mathematischen Modellen. Sie benötigen hoch parallele Simulationen und Machine Learning (z.B. um Mikroskopie-Daten zu entrauschen und mehr Farben gleichzeitig darzustellen). Lennart drückt es im Gespräch so aus: "Ich hab keine Disziplin mehr, ich habe nur noch Fragen." Die beiden Teile seiner Arbeit unterscheiden sich stark: Im Labor sind Gruppentreffen nötig, weil alle aufeinander angewiesen sind. Es wird viel geredet und präzise Handarbeit ist wichtig. In der theoretischen Arbeit ist man auf sich selbst angewiesen und es gibt weniger Interaktion. Any doubts #activematter is a relevant framework to understand nuclear and chromatin organization? Please look at this time-lapse. Zebrafish blastula nucleus, DNA label is Hoechst 33342, single optical section, recorded last night using @VisiTech_UK iSIM. @LennartHilbert, 16.3.2019 Literatur und weiterführende Informationen Y. Sate e.a.: Quantitative measurements of chromatin modification dynamics during zygotic genome activation, bioRxiv preprint, 2019. Lennart Hilbert: Stress-induced hypermutation as a physical property of life, a force of natural selection and its role in four thought experiments. Physical Biology 10(2):026001, 2013 Portrait of Science über Lennart Teil 1 Portrait of Science über Lennart Teil 2 A. Lampe: Hochauflösungsmikroskopie, Die kleinen Dinge, ScienceBlogs, 2017. A. Lampe: Es sind die kleinen Dinge im Leben, 33c3, 2016. Podcasts T. Hagedorn, G. Thäter: MathSEE, Gespräch im Modellansatz Podcast, Folge 205, Fakultät für Mathematik, Karlsruher Institut für Technologie (KIT), 2019. M. Gonciarz, G. Thäter: Portrait of Science, Gespräch im Modellansatz Podcast, Folge 197, Fakultät für Mathematik, Karlsruher Institut für Technologie (KIT), 2019. G. Thäter, K. Page: Embryonic Patterns, Gespräch im Modellansatz Podcast, Folge 161, Fakultät für Mathematik, Karlsruher Institut für Technologie (KIT), 2018. Omega Tau-Podcast 072: Forschung in der Zellbiologie, 2011. J. Schmoranze, I. Wessolowski: Beim Herrn der Mikroskope – AMBIO Core Facility, Sciencekompass Podcast, Episode 009 B, 2017.

Heather looks back at the times when she didn't fit in, and describes how she ultimately found her perfect place. Theme music "Storyteller" by Jahzzar. Used by permission under a Creative Commons license. Find more of his music at @jahzzar.

Today's guest is Tim Mclean. Tim is our first guest from Australia and is the Principal and Managing Director of TXM Lean Solutions. In his mid 20's Tim was promoted in to a Plant Management role and this lead to senior operations and general management positions at Hoechst and in major Blue Chip companies including PPG Industries, Carter Holt Harvey and Amcor. In these roles, Tim continued to increase his knowledge of continuous improvement and lean methodologies and successfully apply these approaches to achieve breakthrough improvements in operations that he was managing.  

Chemotherapeutic treatment of hepatocellular carcinoma often leads to chemoresistance during therapy or upon relapse of tumors. For the development of better treatments, a better understanding of biochemical changes in the resistant tumors is needed. Therefore, especially in vivo models are very important tools to generate standardized cell-material, which can be examined by high throughput techniques. Thus, it should be possible to find new targets for therapy or even for diagnostic. This thesis focusses on the characterization of the in vivo chemoresistant human hepatocellular carcinoma HUH-REISO established from a metronomically cyclophosphamide (CPA) treated HUH7 xenograft mouse model. First step of the work was the establishment of the xenograft mouse model. SCID mice bearing subcutaneous HUH7 tumors were treated i.p. with 75 mg/kg CPA every six days. After 10 weeks of response to the therapy, the tumor growth relapsed and tissue grew with very fast doubling time again, despite of ongoing treatment. This aggressive manner of growth under therapy could be also observed in a re-implantation study where the reisolated CPA chemoresistant HUH-REISO tumors grew without a lag phase, indicating an endogenous imprinted component. To evaluate this, tumors were examined by immunohistochemistry, a functional blood-flow Hoechst dye assay, and qRT-PCR for ALDH-1, Notch-1, Notch-3, HES-1, Thy-1, Oct-4, Sox-2 and Nanog mRNA levels. Histochemical analysis of HUH-REISO tumors revealed significant changes in host vascularization of tumors and especially in expression of the tumor-derived human endothelial marker gene PECAM-1/CD31 in HUH-REISO in comparison to parental HUH-7 cells and in vivo passaged HUH-PAS cells (in vivo grown without chemotherapeutic CPA pressure). The pronounced network of host murine vascularization in parental HUH-7 tumors was completely substituted by a network of human and murine vessel-like structures in HUH-REISO tumors under therapy. In addition, cell lines of these tumors were analyzed in endothelial trans-differentiation studies on matrigel. In those studies with limited oxygen and metabolite diffusion, followed by a matrigel assay, only the chemoresistant HUH-REISO cells exhibited tube formation potential and expression of human endothelial markers ICAM-2 and PECAM-1/CD31. Such a trans-differentiation capacity requires a lineage of cells with pluripotent capacities like so called tumor stem cells. Indeed, I could show in a comparative study on stemness and plasticity markers that Thy-1, Oct-4, Sox-2 and Nanog were upregulated in resistant xenografts. Furthermore, under therapeutic pressure by CPA, tumors of HUH-PAS and HUH-REISO displayed regulations in Notch-1 and Notch-3 expression, which I could also show by qRT-PCR. Notch-1 raised in HUH-PAS under therapeutic pressure, meanwhile it was conversely regulated in comparison to Thy-1, Oct-4, Sox-2 and Nanog in HUH-REISO. In both groups Notch-3 was inducible by 2 times CPA treatment and fell back on base level after further four therapeutic cycles in HUH-REISO. To conclude all these finding: chemoresistance of HUH-REISO was not manifested under standard in vitro, but only under in vivo conditions. HUH-REISO cells showed increased pluripotent capacities and the ability of trans-differentiation to endothelial like cells in vitro and in vivo. These cells expressed typical endothelial surface marker and functionality. Although the mechanism behind chemoresistance of HUH-REISO and involvement of plasticity remains to be clarified, we hypothesize that the observed Notch regulations and upregulation of stemness genes in resistant xenografts are involved in the observed cell plasticity.

Danidel is a 3 times Salesforce MVP, avid Salesforce user, administrator, and developer. He  also helps lead the Salt Lake City area Salesforce User Group.  He blogs at http://www.verticalcoder.com/ tweets at https://twitter.com/dhoechst and codes at https://github.com/dhoechst     Topics covered How he learned Force.com and the importance of Twitter in the process.   Team Development  Continuous Integration with Drone.io and BitBucket. Tools for working with git - SourceTree Books for learning git:  Pro Git IDE tools - MavensMate/Sublime   Remote Objects    What you can do with them Changes to Remote Objects coming in Summer '14 Integrating Salesforce with your Fax Server.  Yes, really.   Apex Testing Tips and his Salesforce Test-Factory framework   Importance of Assertions SeeAllData and avoiding it. Daniel's Salesforce Test-Factory framework https://github.com/dhoechst/Salesforce-Test-Factory    

The cancer stem cell hypothesis implicates that tumor cell population is heterogeneous with relatively well-differentiated cells and poorly-differentiated cells. Only the small population of tumourigenic poorly-differentiated CSCs can escape the normal limits of self-renewal and has the ability to proliferate and maintain the malignant growth of the tumor. One characteristic of stem cell is that the ability to exclude DNA dyes, such as Hoechst 33342 via the over-expression of ATP-binding cassette transporters (ABC transporters) on the cell membrane. It makes the detecting of the stem cell possible. After the Hoechst 33342 staining, stem cells extrude this dye and show a typical profile of low fluorescence in Hoechst red versus Hoechst blue bivariate dot plots. These low Hoechst 33342 stained cells are named as side population (SP) cells. This characteristic has enabled purification and characterization of CSCs when carried out alone or in combination with stem cell surface markers. The CSC hypothesis could have a fundamental influence on cancer therapy. CSCs have shown significant substantial resistance to conventional chemotherapy in contrast to the differentiated cancer cells. It is essential to design a complete therapy strategy first to reduce or minimize proliferating cell mass and then to differentiate or eliminate CSCs, so that the relapses of metastatic cancers could be prevented. This work aimed at investigating if Hedgehog pathway inhibitor GDC-0449 is effective in the lung cancer cell lines HCC (adeno-carcinoma) and H1339 (small cell lung carcinoma) and also the cisplatin resistant lung cancer cells, and if possible effects of GDC-0449 are mediated via SPs. Furthermore, the effect of GDC-0449 on the calcium homeostasis was also investigated. GDC-0449 showed dose-dependent inhibitory effects on cell growth in both HCC and H1339 cells. The combination of GDC-0449 and cisplatin gave an additional inhibitory effect. GDC- 0449 could also inhibit the cell growth in cisplatin resistant HCC and H1339 cells. SP cells as cancer stem-cell-like cells could be found in HCC and H1339 cells. Only the SP cells showed the repopulation ability but not the non-SP cells. GDC-0449 could inhibit the SP cell fraction in both HCC and H1339 cells. So the inhibitory effect of GDC-0449 on cell growth may be mediated via SP. GDC-0449 affected the expression of the Hh pathway components in both HCC and H1339 cells. In HCC cells, GDC-0449 inhibited the activity of the Hh pathway and the down- regulation of Shh, Patched and Gli-1 could be shown. In H1339 cells, GDC-0449 could also inhibit the pathway activity and decrease the expression of Gli-1 in an autocrine pattern due to the over-expression of Shh. The inhibition of Hh pathway increased the expression of Bmi-1 to compensate the loss of Hh pathway function. The Hh pathway activity could be detected only in SP cells from HCC and H1339 cells. The application of GDC-0449 on HCC and H1339 naïve and cisplatin resistant cells increased [Ca2+]c by decreasing [Ca2+]ER. GDC-0449 induced Ca2+ release from ER into cytoplasm in HCC and H1339 naïve and cisplatin resistant cells. The Ca2+ overload could lead to apoptosis, which was related to the cell growth inhibitory effect of GDC-0449 in lung cancer cells. The expression of SERCA and IP3R was not detectably influenced by GDC-0449. The effect of GDC-0449 on lung cancer cell Ca2+ -regulating machinery was not via the alternation of the expression of ER Ca2+ regulating channels.

Background: Chemotherapeutic treatment of hepatocellular carcinoma often leads to chemoresistance during therapy or upon relapse of tumors. For the development of better treatments a better understanding of biochemical changes in the resistant tumors is needed. In this study, we focus on the characterization of in vivo chemoresistant human hepatocellular carcinoma HUH-REISO established from a metronomically cyclophosphamide (CPA) treated HUH7 xenograft model. Methods: SCID mice bearing subcutaneous HUH7 tumors were treated i.p. with 75 mg/kg CPA every six days. Tumors were evaluated by immunohistochemistry, a functional blood-flow Hoechst dye assay, and qRT-PCR for ALDH-1, Notch-1, Notch-3, HES-1, Thy-1, Oct-4, Sox-2 and Nanog mRNA levels. Cell lines of these tumors were analyzed by qRT-PCR and in endothelial transdifferentiation studies on matrigel. Results: HUH-REISO cells, although slightly more sensitive against activated CPA in vitro than parental HUH-7 cells, fully retained their in vivo CPA chemoresistance upon xenografting into SCID mice. Histochemical analysis of HUH-REISO tumors in comparison to parental HUH-7 cells and passaged HUH-PAS cells (in vivo passaged without chemotherapeutic pressure) revealed significant changes in host vascularization of tumors and especially in expression of the tumor-derived human endothelial marker gene PECAM-1/CD31 in HUH-REISO. In transdifferentiation studies with limited oxygen and metabolite diffusion, followed by a matrigel assay, only the chemoresistant HUH-REISO cells exhibited tube formation potential and expression of human endothelial markers ICAM-2 and PECAM-1/CD31. A comparative study on stemness and plasticity markers revealed upregulation of Thy-1, Oct-4, Sox-2 and Nanog in resistant xenografts. Under therapeutic pressure by CPA, tumors of HUH-PAS and HUH-REISO displayed regulations in Notch-1 and Notch-3 expression. Conclusions: Chemoresistance of HUH-REISO was not manifested under standard in vitro but under in vivo conditions. HUH-REISO cells showed increased pluripotent capacities and the ability of transdifferentiation to endothelial like cells in vitro and in vivo. These cells expressed typical endothelial surface marker and functionality. Although the mechanism behind chemoresistance of HUH-REISO and involvement of plasticity remains to be clarified, we hypothesize that the observed Notch regulations and upregulation of stemness genes in resistant xenografts are involved in the observed cell plasticity.

Erufosin (Erucylphosphohomocholin, ErPC3) ist ein neuer Wirkstoff aus der Substanzklasse der Alkylphosphocholine, deren Angriffspunkt nicht die DNA, sondern die Zellmembran ist. Die Alkylphosphocholine lagern sich dort ein, beeinflussen die Lipidzusammensetzung, den Lipidmetabolismus und agieren durch Beeinflussung von intrazellulären Signalwegen unter anderem als Apoptoseinduktoren. Seit Januar 2004 wird mit Erufosin eine Phase I Studie durchgeführt (Dr. med. Lars Lindner, Medizinische Klinik und Poliklinik III, Klinikum Großhadern, LMU München, unpubliziert). Nach Abschluss der Studie wird sich für die folgenden Phase II Studien die Frage nach möglichen Kombinationsmöglichkeiten mit klassischer Chemotherapie oder auch Strahlentherapie stellen. Aufgrund der fehlenden myelosuppressiven Aktivität und der bislang guten Verträglichkeit (fehlende gastrointestinale Toxizität) eignet sich Erufosin insbesondere als Kombinationspartner für weitere toxische Therapieprinzipien wie z.B. Strahlentherapie. Für verschiedene andere, zum Teil bereits klinisch eingesetzte Alkylphosphocholine (Miltefosin®, Perifosin®) konnte in vitro gezeigt werden, dass sie die strahleninduzierte Apoptose verstärken und das klonogene Gesamtüberleben reduzieren, beides zum Teil sogar synergistisch. Eine Phase I Studie zum Einsatz von Strahlentherapie und Perifosin® wurde in den Niederlanden durchgeführt. Die Ergebnisse zeigen eine gute Verträglichkeit der Kombinationsbehandlung (Vink, Schellens et al. 2006). In dieser Arbeit wurde anhand von Zellkulturexperimenten an 14 humanen Zelllinien von für Strahlentherapie in Frage kommenden Tumorentitäten die Kombinationswirkung von Erufosin und Strahlentherapie untersucht. Um die Bestimmung des klonogenen Überlebens zu simulieren wurde das WST1-Zellproliferationsassay verwendet. Die Tumorzellen wurden in einer 96-well-Platte ausgesät, mit Erufosin und Bestrahlung behandelt und die Zellzahl nach 5-8 Tagen Inkubation mit WST1-Reagenz gemessen. Dabei handelt es sich um eine Substanz, die von lebenden Zellen verstoffwechselt wird und der Metabolit photometrisch mit dem ELISA-Reader bestimmt werden kann. Zusätzlich wurde bei 6 Zelllinien die Auswirkung der Kombinationsbehandlung auf die frühe Apoptoseinduktion untersucht. Hierzu wurden die Zellen ausgesät, behandelt und nach 48h mit Propidiumiodid und Hoechst 33342 angefärbt. Die Auswertung erfolgte durch Auszählung der apoptotischen Zellen am Fluoreszenzmikroskop. Zur Quantifizierung der Kombinationseffekte wurde die isobolographische Analyse eingesetzt. Alle untersuchten Zelllinien zeigten in unterschiedlicher Empfindlichkeit ein Ansprechen auf Bestrahlung und Erufosin. Die Strahlenwirkung konnte durch Zugabe von Erufosin verstärkt werden, so dass das mehr Tumorzellen abstarben bzw. die frühe Apoptoseinduktion zunahm. In der isobolographischen Analyse ergaben sich subadditive bis additive Effekt. Besonders empfindlich für die Kombinationsbehandlung zeigten sich mit additiven Effekten A-549 (Bronchial-Ca), MCF-7 (Mamma-Ca), SK-LMS1 (Leiomyosarkom), NCI-H460 (Bronchial-Ca), DU-145 (Prostata-Ca), RD-ES (Ewing-Sarkom), KB (Zervix-Ca), FADU (Pharynx-Ca). Angesichts der Verstärkung des Strahleneffekts im Bezug auf Gesamtüberleben, der frühen Apoptoseinduktion bei Tumorzellen und dem bisher viel versprechenden Einsatz in der Klinik sollte die Kombination aus Erufosin und Strahlentherapie experimentell und klinisch weiter evaluiert werden.

The objective of this work was to examine follicular and oocyte growth in canine ovaries with light and electron microscopic techniques and to characterize canine oocytes during in vitro maturation. Ovaries of healthy bitches of different ages (4 months to 12.5 years)and breeds were used, which had undergone elective ovariohysterectomy at local veterinary clinics. The ovaries of 15 bitches were fixed in Bouin`s solution or paraformaldehyde (4%) for immunohistochemical studies and of three bitches in Karnovsky`s solution for electron microscopic evaluation. COCs and oocytes were recovered from 61 other bitches by slicing the ovaries. They were then examined before and after in vitro maturation (24 to 72 hours) in modified TCM-199 either by native evaluation or after fixation in paraformaldehyde (4%) and nuclear staining (propidium iodide/Hoechst 33342), immunofluorescence or glycohistochemistry. The evaluation of the fluorescence microscopic staining was performed by confocal laser scanning microscopy. Oocytes and COCs after 0, 24, 72 and 90 hours of in vitro maturation were also subjected to electron microscopic examination. The morphology of the canine ovary in light and electron microscopic aspects is comparable to that of other domestic animals. Primordial, primary, secondary and tertiary follicles were regularly seen. The diameter of the oocytes and of the germinal vesicle, as well as the thickness of the zona pellucida, clearly increases during oocyte development. Growing canine oocytes are characterized ultrastructurally by rapid growth in the number of cellular organelles, particularly mitochondria, smooth endoplasmatic reticulum and lipid droplets. Mitotic division starting at the primary follicle stage can be regularly observed by immunostaining with the proliferation marker Ki-67. Further immunohistochemical studies on ovaries indicate that estrogen receptors alpha and beta, as well as MMP-1, -2, -14 and TIMP-2 show a specific distribution in bitches. Canine oocytes could easily be isolated by slicing the ovaries. The number of recovered oocytes was clearly influenced by the age of the donor bitch but not by the breed, the reproductive status or the transportation time between time of surgery in the veterinary clinic and the recovery of the oocytes in the laboratory. 48% of all isolated oocytes had a dark homogenous ooplasm and multiple dense layers of cumulus cells. After in vitro maturation, morphological changes like the formation of vesicles and the loss of cumulus cells could be observed in most of the COCs. Immediately after recovery, the nuclei of all oocytes were at the germinal vesicle stage, although the chromatin showed different degrees of condensation. While first signs of the resumption of meiosis were seen after 24 hours of culture, only one oocyte in metaphase II could be seen after 72 hours. Nuclear and cytoplasmatic maturation could be detected by electron microscopy for up to 24 hours of in vitro culture, as well as signs of degeneration, which were even more prominent after longer culture periods. The immunoreaction of ZP3beta, alpha-Tubulin and Connexin 43 and the binding sites of the lectins WGA and SBA showed characteristic changes in canine oocytes and COCs before and after in vitro maturation.

Die vorliegende Arbeit beschäftigt sich mit der funktionellen und molekularen Charakterisierung von humanen CD34- Zelllinien aus dem peripheren Blut (V54/1, V54/2) im Vergleich zu den aus dem Knochenmark etablierten Zelllinien (L87/4, L88/5). Die Klone V54/1 und V54/2 wurden aus dem peripheren Blut nach Stammzellmobilisierung und CD6 Depletion durch Zugabe eines Faktorengemisches aus IL-1b, IL-3, IL-6, IL-7, IL-8 und IL-11 erzeugt. L87/4 und L88/5 hingegen sind adhärente und wachstumsarretierte Stromazellen, die die Erhaltung und Differenzierung von hämatopoetischen Vorläuferzellen durch Mediatoren ermöglichen (Thalmeier et al. 2000). Das Ziel dieser Arbeit war die Untersuchung von Stammzelleigenschaften bei den Zelllinien L87/4, L88/5, V54/1 und V54/2. Dazu soll die Färbung mit den Farbstoffen Rhodamin 123 (Rh123) und Hoechst 33342 zeigen, ob Subpopulationen innerhalb der Klone mit unterschiedlichen Färbeeigenschaften, bestehen. Die biologische Bedeutung der beiden Farbstoffe liegt darin, dass Sie dazu geeignet sind frühe Stammzellen zu identifizieren. Als Substrat der P-Glykoproteinpumpe, die u.a. auf frühen Vorläuferzellen mit stark erhöhter Repopulationskapazität gefunden wird, werden diese Farbstoffe aus der Zelle gepumpt. Der Farbstoff-Efflux kommt durch die mdr-Gen-kodierte (multi-drug-resistance) und Kalzium-abhängige P-Glykoproteinpumpe zustande. Das P-Glykoprotein hat neben der Bedeutung in der Stammzellbiologie in der angewandten Medizin eine wichtige Funktion in der Resistenzentwicklung von Tumoren. Des weiteren wurden bei den Zelllinien stammzellrelevante Oberflächenantigene (CD10, CD34, CD14, CD105, SH3 und CD117) untersucht, um Unterschiede zwischen L87/4, L88/5 und den Klonen V54/1, V54/2 zu erkennen. Versuche zur Induktion der Differenzierung sollten Hinweise auf die Plastizität der Zelllinien geben. Experimente an den durch den Rh123-Efflux unterscheidbaren Subpopulationen der Zelllinie V54/2 dienen der Aufklärung von Unterschieden in Morphe, zellulären Transportfunktionen und Funktionseinheiten von Transkriptionsfaktor Netzwerken. Methodisch wurde für die Analyse der Epitope und der Färbungen mit Rh123 und Hoechst 33342 ein Durchflußzytometer verwendet. Die Analyse der Funktionseinheiten von Transkriptionsfaktor Netzwerken wurde mittels Reverse Transkriptase Polymerase Ketten Reaktion durchgeführt. Die Ergebnisse der Färbeexperimente zeigten, dass bei allen untersuchten Zelllinien durch eine unterschiedliche Anfärbbarkeit der Zellen mit dem Farbstoff Rh123 zwei Subpopulationen unterschieden werden können. Die jeweils größere Subpopulation der Zelllinien färbt sich mit Rh123 an und bleibt auch nach einer definierten Inkubationszeit, die den Rh123-Efflux ermöglichen soll, gefärbt. Sie wird Rh123high genannt. Die übrigen Zellen, die bei allen Zelllinien unter 10% der Gesamtpopulation betragen, sind in der Lage den Farbstoff aus der Zelle zu pumpen. Diese Subpopulation wird Rh123low genannt und ist mit Stammzelleigenschaften wie tausendfach erhöhter Repopulationsfähigkeit in NOD/SCID-Mäusen assoziiert. Es konnte also innerhalb der untersuchten monoklonalen Linien eine Rh123low Subpopulation identifiziert werden, die sich durch zahlreiche biologische Eigenschaften von der Gesamtpopulation unterscheidet. Da der Rh123 Efflux durch eine Kalzium-abhängige Pumpe zustande kommt, lässt sie sich durch den Kalziumantagonisten Verapamil hemmen. Eine Hemmung der Pumpe bewirkt, dass die Rh123low Zellen nicht mehr in der Lage sind Rh123 aus der Zelle zu pumpen, so dass sie nach einer definierten Inkubationszeit mit Rh123 gefärbt bleiben. Neben diesem funktionellen Beweis für die P-Glykoproteinpumpe konnte durch den strukturellen Nachweis der Pumpe mittels eines Antikörpers gegen P-Glykoprotein ein definitiver Beweis für das Vorhandensein der aktiven P-Glykoproteinpumpe bei der Rh123low Population erbracht werden. Mit dem anderen Farbstoff Hoechst 33342 können die jeweiligen Anteile der Zelllinien in den einzelnen Stadien des Zellzyklus nachgewiesen und zudem ein kleiner Anteil an Zellen bestimmt werden, der als „Side Population“ (SP-Zellen) definiert wird. Diesen SP-Zellen werden Eigenschaften von aktiven Stammzellen zugeschrieben. Hierbei besteht ein Unterschied zwischen den aus dem Knochenmark und den aus dem peripheren Blut etablierten Linien, da die Zellen aus dem peripheren Blut nicht nur ein anderes Zellzyklusmuster aufweisen, sondern auch einen höheren Anteil an SP-Zellen besitzen. Es wurden vergleichende Untersuchungen zwischen den Zelllinien und zwischen den Rh123high und Rh123low Subpopulationen innerhalb einer Zelllinie mit Antikörpern gegen die Epitope CD14, CD45, HLA-DR, CD10, CD117, CD105 und SH3 durchgeführt. Dabei waren CD14 und CD45 auf allen Zelllinien negativ, wobei alle Zelllinien eine positive Expression für den mesenchymalen Marker Endoglin (CD105) und für SH3 (CD73) zeigten. CD117 konnte nur auf den aus dem Knochenmark etablierten Zelllinien L87/4 und L88/5 nachgewiesen werden. CD34, ein charakteristischer Marker für hämatopoetische Vorläuferzellen, aber auch für Endothelzellen, konnte nur auf den Zellen der Rh123low Subpopulation nachgewiesen werden. Im Gegensatz dazu exprimieren die Rh123high Zellen kein CD34. Da es sich bei den Zelllinien um Klone handelt, ist der Unterschied in der Expression von CD34 zwischen der Rh123low und der Rh123high Population ein deutlicher Hinweis auf die Plastizität der Zelllinien und das Fließgleichgewicht zwischen Rh123low und Rh123high. Durch eine Zellsortierung der Zelllinie V54/2 wurde die Rh123low von der Rh123high Subpopulation getrennt, um sie dann bezüglich ihrer Morphologie, dem Wachstum in Methylzellulose und der Expression ausgewählter Funktionseinheiten von Transkriptionsfaktor Netzwerken zu untersuchen. Dabei erhärtete sich die Hypothese, dass es sich bei der Rh123low Subpopulation um aktivere Zellen mit einer gesteigerten Expression von erythroid/myeloischen und mesodermalen Eingaben (z.B. VEGF, BMP-4), Rezeptoren (z.B. tie-1), vernetzter Transkriptionsfaktoren (z.B. GATA, ETS) und letztendlich Ausgaben (z.B. PECAM) handelt. Diese fungieren in Netzwerken mit dem Ziel, stammzellrelevante Funktionen zu ermöglichen. Die Morphologie zeigte in den Zytozentrifugationspräparaten deutliche Unterschiede zwischen Zellen der Rh123low und der Rh123high Subpopulation. Die Rh123low Subpopulation besteht aus lymphoid-ähnlichen Zellen, was für Zellen mit Stammzellfunktion charakteristisch ist. Die Rh123high Subpopulation dagegen hat ein insgesamt größeres Zellvolumen und einen gebuchteten Kern mit perinukleärer Aufhellung. Untersuchungen des klonalen Wachstums in der Methylzellulose ergaben bei keiner der Subpopulationen eine wesentliche Koloniebildung. Durch die Inkubation der Zelllinie V54/2 mit dem Neurotropen Wachstumsfaktor (NGF) konnte eine morphologische Änderung in Richtung einer neuronalen/glialen Differenzierung nach 8-12 Stunden induziert werden. Der immunhistochemische Nachweis von Glial Fibrillary Acidic Protein (GFAP) bestätigte die mesenchymale Potenz zumindest in Richtung einer glialen Differenzierung. Das unterschiedliche Expressionsmuster ausgewählter, für die Differenzierung notwendiger Zusammenspieler innerhalb von Transkriptionsfaktor Netzwerken innerhalb der Rh123high und der Rh123low Population bei V54/2 war ein weiterer Hinweis, dass es sich bei der Rh123low Subpopulation um aktive Vorläuferzellen mit möglicher Stammzellpotenz handelt. In der Rh123low Subpopulation wurde im Gegensatz zur Rh123high Population eine Expression von BMP4, GATA1, GATA3 nachgewiesen, die essentiell für die Hämatopoese und für eine mesenchymale Differenzierung ist. Die Faktoren für GATA2, GATA3, beta globin, Elf-1 und PECAM1 wurden in einem stärkeren Maß in der Rh123low als in der Rh123high Population exprimiert. BMP-Rez., Myb, sowie die Endothel-assoziierten Faktoren Tie-1 und VEGF waren in beiden Subpopulationen gleich stark vorhanden. Bei den wenigen Funktionseinheiten der größeren und Rh123high Population handelt es sich vor allem um angiogenetische Faktoren, was auf eine limitierte Differenzierungseigenschaft der Rh123high Subpopulation und die enge Beziehung zwischen Blut- und Endothelzellen („Hämangioblast“) hinweist. Ein Nachweis für die Plastizität der Stammzellen innerhalb der von uns etablierten Zelllinien wurde dadurch erbracht, dass die zellsortierten Subpopulationen Rh123low und Rh123high nach dem Sortierexperiment getrennt rekultiviert wurden, wobei das Wachstum der Rh123low Subpopulation deutlich langsamer war als das der Rh123high Subpopulation. Nach zwei Wochen wurden die zellsortierten Subpopulationen erneut einer Rh123 Färbung unterzogen, wobei sich wiederum das ursprüngliche Verhältnis zwischen den Rh123low und Rh123high Subpopulationen einstellte. So kann man aus der Transdifferenzierung der Zelllinien von Rh123low in Rh123high und umgekehrt die Plastizität der hier untersuchten adulten Stammzelllinien ableiten. Die Ergebnisse sollen zum grundlegenden Verständnis der Biologie adulter (nicht embryonaler) Stammzellen beitragen und damit die Möglichkeit schaffen, adulte Stammzellen bzw. deren Subpopulationen gezielt für einen reparativen Gewebe- und Organersatz zu verwenden. Dabei liefern sie die Basis für weitergehende Untersuchungen zum besseren Verständnis der physiologischen und regenerativen Vorgänge, z.B. auch bei Alterung oder bei gesteigerter Funktion. Darüber hinaus kann aufgrund der vorliegenden Ergebnisse durch weitere Untersuchungen möglicherweise besser verstanden werden, ob es gelingen kann das Potential adulter Stammzellen zur therapeutischen Gewebereparation, z.B. zur Verhinderung oder Verringerung einer Narbenbildung, zu nutzen.

Modern light microscopical techniques were employed to follow dynamical nuclear processes during the cell cycle and during DNA-repair. Laser-UVA-microirradiation The protein Rad51 is essential for the repair of double-strand breaks (DSBs) via the conservative homologous recombination repair pathway. To test the hypothesis that Rad51 localizes to damaged sites during DSB repair, a laser-UVA-microirradiation system was established. With this system spots with sizes around 1 µm in nuclei of living cells can be irradiated with UVA-light. After sensitization of cells by incorporation of BrdU into nuclear DNA and staining with the live cell dye Hoechst 33258, the system can be used to introduce double-strand breaks and single-strand breaks in the irradiated spots. The response of Rad51 to microirradiation By use of laser-UVA microirradiation the localization of Rad51 at damaged sites containing DNA double-strand breaks could be demonstrated. The accumulation of Rad51 at microirradiated sites was followed in cells fixed at increasing times after microirradiation. First Rad51 accumulations were visible 5 - 10 minutes after irradiation, and the number of cells with Rad51 accumulations increased until a plateau was reached 20 - 30 minutes after irradiation. In contrast, the majority of irradiated cells had accumulations of Mre11 protein already 5 - 10 minutes after irradiation. This is consistent with reports that nuclear Mre11 foci appeared early in the response to ionizing radiation, but absolute response times were faster after microirradiation than after ionizing radiation. Large-scale nuclear patterns were microirradiated, and Rad51 accumulations that reflected the shape of the irradiated patterns were found up to eight hours after irradiation. This conservation of the pattern of Rad51 accumulations, which reflect sites containing the damaged DNA, indicated that the chromatin in the irradiated cells performs no large scale reordering in response to DNA damage. The dynamics of chromosomes and chromosome territories In 1909 Theodor Boveri forwarded the hypothesis that arrangements of chromosome territories (CTs) are stably maintained during interphase, but subject to changes during mitosis. In the last decade several groups reported evidence for the stability of CT arrangements, but considerable movements of chromosomal subregions were also observed. The data concerning the maintenance or reordering of CTs during mitosis have been contradictory. Live cell imaging To follow the movements of chromosomes and CTs, a novel experimental approach was taken. Cells expressing a fusion protein of the core histone H2B with GFP (H2B-GFP) stably incorporate H2B-GFP into nucleosomes. In these cells chromatin regions were selectively marked by laser-photobleaching and followed by live cell microscopy. To this end, a live cell imaging system was established at a confocal laser-scanning microscope, which allows the observation of living cells for several days. Chromatin movements visualized by photobleached H2B-GFP To track possible movements in interphase cell nuclei, stripe patterns were bleached into nuclei at several stages of interphase. These patterns were retained for up to two hours, until they became invisible due to the replacement of bleached H2B-GFP by unbleached H2B-GFP, supporting the hypothesis that CT order is stably maintained during interphase. Nuclei, in which all chromatin except for a contiguous zone at one nuclear pole was bleached, were followed through mitosis. At prophase a number of unbleached chromosomal segments became visible. The segments showed a variable degree of clustering in metaphase. When daughter nuclei were formed, the segments locally decondensed into patches of unbleached chromatin. In all daughter cells the patches were separated by bleached chromatin, and clustered to a variable extent. These observations support the hypothesis that changes of chromosome neighborhoods occur during mitosis and that CT neighborhoods can profoundly vary from one cell cycle to the next.

Asynchrononously growing cells of a M3-1 Chinese hamster line were ultraviolet (UV) irradiated ( = 254 nm) with UV fluences up to 7.5 J/m2. After irradiation, cells were incubated with or without 2 mM caffeine for 20 hr, then mitotic cells were selected by mechanical shaking. Their chromosomes were isolated, stained with Hoechst 33258 and chromomycin A3, and measured flow cytometrically. While the fluorescence distributions of chromosomes (flow karyotypes) from cells treated with UV alone or with caffeine alone were very similar to those of untreated controls, the flow karyo-types of UV + caffeine-treated cells showed a debris continuum that increased with increasing UV fluence suggesting an increased number of chromosome fragments. Visual evaluation of metaphase plates revealed that the percentage of cells with chromosome damage also increased steadily with increasing UV fluence. A high degree of correlation was observed between the relative magnitude of the debris level from flow karyotypes and the percentage of cells with chromosome damage and with generalized chromosome shattering, respectively, as determined from metaphase spreads.