Evaluationsbericht ARIADNEphil: Ergebnisse zur Pilotphase des Mentoring-Programms für Nachwuchswissenschaftlerinnen an der Philosophischen Fakultät und Fachbereich Theologie der Friedrich-Alexander-Universität Erlangen-Nürnberg

"Der vorliegende Bericht stellt die Ergebnisse der Evaluation der Pilotphase des ARIADNEphilMentoring-Programms an der Philosophischen Fakultät und Fachbereich Theologie der Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) vor. Dieses erste Mentoring-Programm für engagierte Nachwuchswissenschaftlerinnen an der Philosophischen Fakultät und Fachbereich Theologie, das Studentinnen ebenso förderte wie Doktorandinnen und Habilitandinnen, begann am 21. Januar 2009 mit einer Auftakt- und endete am 28. April 2010 mit einer Abschlussveranstaltung. In diesem Zeitraum wurden 43 Mentees verschiedener Qualifikationsstufen von 37 erfahreneren WissenschaftlerInnen bei Planung, Beginn und Durchführung ihrer wissenschaftlichen Karriere begleitet. Unterstützt wurde diese Mentoring-Phase durch ein detailliert ausgestaltetes Rahmenprogramm, das den TeilnehmerInnen durch verschiedene Workshops, 'Stammtische' und Seminare die Möglichkeit bot, Schlüsselqualifikationen und informelles Handlungswissen im wissenschaftlichen Arbeitsumfeld weiterzugeben (MentorInnen) oder zu erlangen (Mentees). Die Ausgestaltung und der Ablauf der Pilotphase von ARIADNEphil sind in diesem Bericht festgehalten. Sein Kernstück stellt allerdings die Darstellung von fünf programmbegleitend durchgeführten Onlinebefragungen und ihrer Ergebnisse dar. Drei dieser Befragungen richteten sich an Mentees, zwei an die MentorInnen. Hauptsächlich wurden dabei Angaben zu den Erwartungen der TeilnehmerInnen, zur Zufriedenheit mit der Rahmenprogrammgestaltung und der eingegangenen Mentoringbeziehung sowie zur wahrgenommenen Umsetzung der im ARIADNEphil-Mentoring-Programm vorgesehenen Ziele erhoben. (...)" (Textauszug

Lipopolysaccharide induced inflammation in the perivascular space in lungs

<p>Abstract</p> <p>Background</p> <p>Lipopolysaccharide (LPS) contained in tobacco smoke and a variety of environmental and occupational dusts is a toxic agent causing lung inflammation characterized by migration of neutrophils and monocytes into alveoli. Although migration of inflammatory cells into alveoli of LPS-treated rats is well characterized, the dynamics of their accumulation in the perivascular space (PVS) leading to a perivascular inflammation (PVI) of pulmonary arteries is not well described.</p> <p>Methods</p> <p>Therefore, we investigated migration of neutrophils and monocytes into PVS in lungs of male Sprague-Dawley rats treated intratracheally with <it>E. coli </it>LPS and euthanized after 1, 6, 12, 24 and 36 hours. Control rats were treated with endotoxin-free saline. H&E stained slides were made and immunohistochemistry was performed using a monocyte marker and the chemokine Monocyte-Chemoattractant-Protein-1 (MCP-1). Computer-assisted microscopy was performed to count infiltrating cells.</p> <p>Results</p> <p>Surprisingly, the periarterial infiltration was not a constant finding in each animal although LPS-induced alveolitis was present. A clear tendency was observed that neutrophils were appearing in the PVS first within 6 hours after LPS application and were decreasing at later time points. In contrast, mononuclear cell infiltration was observed after 24 hours. In addition, MCP-1 expression was present in perivascular capillaries, arteries and the epithelium.</p> <p>Conclusion</p> <p>PVI might be a certain lung reaction pattern in the defense to infectious attacks.</p

Clonal Hematopoiesis after Autologous Stem Cell Transplantation Does Not Confer Adverse Prognosis in Patients with AML.

INTRODUCTION Despite a 50% cure rate, relapse remains the main cause of death in patients with acute myeloid leukemia (AML) consolidated with autologous stem cell transplantation (ASCT) in first remission (CR1). Clonal hematopoiesis of indeterminate potential (CH) increases the risk for hematological and cardiovascular disorders and death. The impact of CH persisting after ASCT in AML patients is unclear. MATERIALS AND METHODS We retrospectively investigated the prognostic value of persisting DNMT3A, TET2, or ASXL1 (DTA) mutations after ASCT. Patients underwent stratification depending on the presence of DTA mutations. RESULTS We investigated 110 consecutive AML patients receiving ASCT in CR1 after two induction cycles at our center between 2007 and 2020. CH-related mutations were present in 31 patients (28.2%) after ASCT. The baseline characteristics were similar between patients with or without persisting DTA mutations after ASCT. The median progression free survival was 26.9 months in patients without DTA mutations and 16.7 months in patients with DTA mutations (HR 0.75 (0.42-1.33), p = 0.287), and the median overall survival was 80.9 and 54.4 months (HR 0.79 (0.41-1.51), p = 0.440), respectively. CONCLUSION We suggest that DTA-CH after ASCT is not associated with an increased risk of relapse or death. The persistence of DTA mutations after induction should not prevent AML patients in CR1 from ASCT consolidation. Independent studies should confirm these data

What is the clinical relevance of different lung compartments?

The lung consists of at least seven compartments with relevance to immune reactions. Compartment 1 - the bronchoalveolar lavage (BAL), which represents the cells of the bronchoalveolar space: From a diagnostic point of view the bronchoalveolar space is the most important because it is easily accessible in laboratory animals, as well as in patients, using BAL. Although this technique has been used for several decades it is still unclear to what extent the BAL represents changes in other lung compartments. Compartment 2 - bronchus-associated lymphoid tissue (BALT): In the healthy, BALT can be found only in childhood. The role of BALT in the development of the mucosal immunity of the pulmonary surfaces has not yet been resolved. However, it might be an important tool for inhalative vaccination strategies. Compartment 3 - conducting airway mucosa: A third compartment is the bronchial epithelium and the submucosa, which both contain a distinct pool of leukocytes (e.g. intraepithelial lymphocytes, IEL). This again is also accessible via bronchoscopy. Compartment 4 - draining lymph nodes/Compartment 5 - lung parenchyma: Transbronchial biopsies are more difficult to perform but provide access to two additional compartments - lymph nodes with the draining lymphatics and lung parenchyma, which roughly means "interstitial" lung tissue. Compartment 6 - the intravascular leukocyte pool: The intravascular compartment lies between the systemic circulation and inflamed lung compartments. Compartment 7 - periarterial space: Finally, there is a unique, lung-specific space around the pulmonary arteries which contains blood and lymph capillaries. There are indications that this "periarterial space" may be involved in the pulmonary host defense

Expression levels of immune markers in Actinobacillus pleuropneumoniae infected pigs and their relation to breed and clinical symptoms

<p>Abstract</p> <p>Background</p> <p>In pigs little is known about the role of innate immune defence in bacterial infections of the respiratory tract, despite their major role in pig production. In the present study we characterized and compared <it>in vitro </it>and <it>in vivo </it>activation of immune markers of different pig breeds 7 days before, and 4 and 21 days after an experimental aerosol infection with <it>Actinobacillus (A.) pleuropneumoniae</it>.</p> <p>Results</p> <p><it>In vitro </it>stimulation of bronchoalveolar lavage fluid (BALF) and blood leukocytes with <it>A. pleuropneumoniae, Streptococcus suis</it>, PMA and LPS led to production of different amounts of H₂O₂, NO and TNF-α, depending on the stimulus, individual, breed and time of infection. Generally, significant responses to <it>in vitro </it>stimulation were observed only in blood leukocytes, whereas the alveolar macrophages showed a high basal activation. In addition, the production of haptoglobin and cytokines (TNF-α, IFN-γ and IL-10) <it>in vivo </it>was measured in plasma and BALF. Plasma haptoglobin levels mirrored the clinical manifestations at 4 days post-infection. In plasma and BALF TNF-α could not be detected, whereas variable levels of IFN-γ were found at pre- and post-infection times. IL-10 was found in some plasma but in none of the BALF samples. The different expression levels in individuals within the breeds correlated for some markers with the severity of clinical manifestations, e.g. H₂O_2,plasma haptoglobin and BALF IFN-γ for German Landrace pigs.</p> <p>Conclusion</p> <p>Our findings revealed differences in the activation of the immune markers with respect to infection time, individuals and breeds. Moreover, results showed different correlation grades between the immune markers produced <it>in vitro </it>or <it>in vivo </it>and the clinical manifestations. Further analyses will have to show whether these markers may serve as correlates of protection against porcine respiratory infections.</p

Evaluationsbericht ARIADNEmed: Ergebnisse zur Pilotphase des Mentoring-Programms für Nachwuchswissenschaftlerinnen an der Medizinischen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg

"Der vorliegende Bericht stellt die Ergebnisse der Evaluation der Pilotphase des ARIADNEmed-Mentoring-Programms der Medizinischen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg vor. Dieses erste Mentoring-Programm für promovierte Wissenschaftlerinnen an der Medizinischen Fakultät begann am 24. Juni 2008 mit einer Einführungsveranstaltung. Seitdem begleiteten 47 habilitierte WissenschaftlerInnen und ProfessorInnen insgesamt 48 Nachwuchswissenschaftlerinnen aus verschiedenen Bereichen der Medizinischen Fakultät auf deren Weg in Richtung Habilitation, unterstützt von einem Rahmenprogramm, das die Mentoringpartnerbeziehungen begleitete und sie optimieren sollte. Die Abschlussveranstaltung der Pilotphase fand am 30. November 2009 statt. Die nachfolgenden Ausführungen geben einen Einblick in das Programm und seine Ausgestaltung. Im Mittelpunkt steht allerdings die Darstellung der Ergebnisse dreier Befragungen aller 95 Beteiligten zum Rahmenprogramm und zur eingegangenen Mentoringbeziehung sowie zu ihren Erwartungen an das Programm und zu ihrer Bewertung der Realisierung des Programms." (Textauszug

The free volume of poly(vinyl methylether) as computed in a wide temperature range and at length scales up to the nanoregion

14 páginas, 12 figuras.In the present work, we focus on the free volume evaluations from different points of view, including the aspect of probe sizes, temperature, and cavity threshold. The free volume structure is analyzed on structures of poly(vinyl methylether) prepared by fully atomistic molecular dynamics. At first, the temperature behavior of an overall free volume and a free volume separated into individual cavities is shown. The origin of large free volume cavities is explained. A complex view on the cavity number is provided, while a complicated behavior previously observed is now explained. The number of large cavities remained almost constant with the temperature. Oppositely, the number of small cavities related to the atomic packing changes with temperature in a distinct way for glassy and supercooled regions. The cavity number maxima determine a percolation threshold according to percolation theory. The change in polymer properties with temperature can be related to a percolation of the free volume according to the free volume theory, when proper probe radii ∼0.8 Å are used for its observation. A construction of probabilistic distribution of free volume sizes is suggested. The free volume distributions reported here are bimodal. The bimodal character is explained by two different packings—atomic and segmental—forming a prepeak and a main peak on the distribution. Further attention is dedicated to comparisons of the computed free volume sizes and the ortho-positronium (o-Ps) lifetimes. The prepeak of the free volume distribution is probably unseen by o-Ps because of a cavity threshold limit. The effect of the shape factor on the computed o-Ps lifetimes is tested. The quasicavities obtained by redistributing the free volume maintain the ratio of the main dimensions with temperature. Finally, novel data on the cavity environment are provided, while it is suggested how these can be useful with the recent developments in the positron annihilation methods. The coordination number of large cavities with the polymer segments is around 1, as predicted in the free volume theory. Similarly to the percolation and the cavity number, the coordination number exhibits a change when explored by a suitable probe radius ∼0.8 Å. The insightful visualizations showed properties of interest investigated within the actual work.This work was supported by Project No. MAT2007– 63681 (Spanish Ministry of Education) and Grant No. IT- 436–07 (Basque Government). Support from Spanish Ministry of Education Grant No. CSD2006-53 is also acknowledged.Peer reviewe

The Conduit System Transports Soluble Antigens from the Afferent Lymph to Resident Dendritic Cells in the T Cell Area of the Lymph Node

AbstractResident dendritic cells (DC) within the T cell area of the lymph node take up soluble antigens that enter via the afferent lymphatics before antigen carrying DC arrive from the periphery. The reticular network within the lymph node is a conduit system forming the infrastructure for the fast delivery of soluble substances from the afferent lymph to the lumen of high endothelial venules (HEVs). Using high-resolution light microscopy and 3D reconstruction, we show here that these conduits are unique basement membrane-like structures ensheathed by fibroblastic reticular cells with occasional resident DC embedded within this cell layer. Conduit-associated DC are capable of taking up and processing soluble antigens transported within the conduits, whereas immigrated mature DC occur remote from the reticular fibers. The conduit system is, therefore, not a closed compartment that shuttles substances through the lymph node but represents the morphological equivalent to the filtering function of the lymph node