52 research outputs found

    The adaptive potential of a plant pathogenic fungus, Rhizoctonia solani AG-3, under heat and fungicide stress

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    The ability to improve fitness via adaptive evolution may be affected by environmental change. We tested this hypothesis in an in vitro experiment with the plant pathogen Rhizoctonia solani Anastomosis Group 3 (AG-3), assessing genetic and environmental variances under two temperatures (optimal and higher than optimal) and three fungicide concentrations (no fungicide, low and high concentration of a copper-based fungicide). We measured the mean daily growth rate, the coefficient of variation for genotypic (I G) and environmental variance (I E) in growth, and broad-sense heritability in growth. Both higher temperature and increased fungicide concentration caused a decline in growth, confirming their potential as stressors for the pathogen. All types of standardized variances in growth—I G, phenotypic variance, and I E as a trend—increased with elevated stress. However, heritability was not significantly higher under enhanced stress because the increase in I G was counterbalanced by somewhat increased I E. The results illustrate that predictions for adaptation under environmental stress may depend on the type of short-term evolvability measure. Because mycelial growth is linked to fitness, I G reflects short-term evolvability better than heritability, and it indicates that the evolutionary potential of R. solani is positively affected by stres

    Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells

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    © 2018, American Society for Clinical Investigation. This article has been published in final form at https://doi.org/10.1172/JCI120612First-generation immune checkpoint inhibitors, including anti-CTLA-4 and anti-programmed death 1 (anti-PD-1) antibodies, have led to major clinical progress, yet resistance frequently leads to treatment failure. Thus, new targets acting on T cells are needed. CD33-related sialic acid-binding immunoglobulin-like lectins (Siglecs) are pattern-recognition immune receptors binding to a range of sialoglycan ligands, which appear to function as self-associated molecular patterns (SAMPs) that suppress autoimmune responses. Siglecs are expressed at very low levels on normal T cells, and these receptors were not until recently considered as interesting targets on T cells for cancer immunotherapy. Here, we show an upregulation of Siglecs, including Siglec-9, on tumor-infiltrating T cells from non-small cell lung cancer (NSCLC), colorectal, and ovarian cancer patients. Siglec-9-expressing T cells coexpressed several inhibitory receptors, including PD-1. Targeting of the sialoglycan-SAMP/Siglec pathway in vitro and in vivo resulted in increased anticancer immunity. T cell expression of Siglec-9 in NSCLC patients correlated with reduced survival, and Siglec-9 polymorphisms showed association with the risk of developing lung and colorectal cancer. Our data identify the sialoglycan-SAMP/Siglec pathway as a potential target for improving T cell activation for immunotherapy.Peer reviewe

    Digitalisierung als Projektionsfläche für Sehnsüchte und Ängste in Narrativen von wohnungslosen Menschen

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    Wenn von Obdach- und Wohnungslosigkeit bedrohte oder betroffene Menschen in Gruppendiskussionen und Interviews über digitale Kommunikations- und Informationstechnologien und deren Potenzial für mögliche (sozialarbeiterische) Hilfe und Unterstützung für ihre jeweilige Situation sprechen, zeigt sich zweierlei: Erstens betrifft die digitale Transformation der Gesellschaft auch wohnungslose Menschen, so dass keine digitale Spaltung zwischen wohnungslosen und nicht wohnungslosen Menschen zu konstatieren ist. Zweitens zeitigt das Reden über Digitalisierung verschiedene Narrative, in denen Digitalisierung als Projektionsfläche für spezifische Ängste und Sehnsüchte konstruiert wird: Einerseits sehen die Diskutierenden digitalisierte Angebote sehr kritisch, da mit ihnen eine punitive und kontrollierende Gesellschaft imaginiert wird, die sich die digitalisierten Daten zu eigen macht, um Überwachung, Strafverfolgung und Vertreibung von wohnungslosen Menschen zu forcieren. Andererseits verbinden die Befragten mit digitaler Kommunikation Utopien einer besseren Gesellschaft, in der sie nicht als Wohnungslose stigmatisiert werden, sondern eine Kommunikation auf Augenhöhe unter Menschen gewährleistet und Autonomie erreichbar wird. (DIPF/Orig.

    Robot-assisted repair of incisional hernia of the abdominal wall: Which access is better—endoscopic totally extraperitoneal preperitoneal plasty (eTEP) or mini- or less-open sublay (e)(MILOS), some first considerations

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    Numerous metanalyses have shown that the retromuscular mesh placement is superior to other positions in terms of recurrence and complication rate. As a result, there has been a surge in novel minimally invasive retromuscular surgical techniques. We compared total extraperitoneal plasty (eTEP) and hybrid Mini/Less-open-Sublay [(e)MILOS] with respect to their adaptability to a surgical robotic system. Unfortunately, there is little to no literature regarding robotic adaptation of the (e)MILOS procedure, which made it rather difficult to juxtapose, but then again also implies that it is not commonly performed. As many benefits as the robot brings to endoscopic surgery, however, there is one major constraint when it comes to directionality. In eTEP dissection is performed in one direction and the trocars are positioned at the edge of the dissection field. The centripetal preparation of the (e)MILOS procedure is less suitable for the currently available systems and would naturally require multiple un- and re-dockings of the robot. Alternatively, the robot could only be used for a minor part of the operation. Looking at the published data concerning laparoendoscopic (e)MILOS and eTEP, there appears to be no significant difference in terms of major complications as well as reoperation and infection rates. However, a comparison to a robot-assisted eTEP cannot be done due to lack of publications. Judging from our own experience, we believe the eTEP technique to harness the advantages of the robot in addition to those of minimally invasive surgery more effectively. Within the last two decades, we have been experiencing a constant increment of endoscopic procedures in hernia surgery. This surge is nonetheless thanks to the availability of robotics in a continuously increasing number of hospitals in Europe and the United States. The combination of the advantages of minimally invasive surgery and robotic systems has been discussed and elaborated on many occasions and platforms. Hence, the goal of this analysis is to compare two broadly established minimally invasive (or less open) retromuscular methods in hernia repair surgery with regard to their adaptability to a surgical robot

    The adaptive potential of a plant pathogenic fungus, Rhizoctonia solani AG-3, under heat and fungicide stress

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    The ability to improve fitness via adaptive evolution may be affected by environmental change. We tested this hypothesis in an in vitro experiment with the plant pathogen Rhizoctonia solani Anastomosis Group 3 (AG-3), assessing genetic and environmental variances under two temperatures (optimal and higher than optimal) and three fungicide concentrations (no fungicide, low and high concentration of a copper-based fungicide). We measured the mean daily growth rate, the coefficient of variation for genotypic (I (G)) and environmental variance (I (E)) in growth, and broad-sense heritability in growth. Both higher temperature and increased fungicide concentration caused a decline in growth, confirming their potential as stressors for the pathogen. All types of standardized variances in growth-I (G), phenotypic variance, and I (E) as a trend-increased with elevated stress. However, heritability was not significantly higher under enhanced stress because the increase in I (G) was counterbalanced by somewhat increased I (E). The results illustrate that predictions for adaptation under environmental stress may depend on the type of short-term evolvability measure. Because mycelial growth is linked to fitness, I (G) reflects short-term evolvability better than heritability, and it indicates that the evolutionary potential of R. solani is positively affected by stress

    Resolution of atelectasis during radiochemotherapy of lung cancer with serious implications for further treatment. A case report

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    Local failure is a major cause for low overall survival rates in advanced non small cell lung cancer (NSCLC). Among others, radioresistant tumor clones as well as geographical miss can explain these high local failure rates. One reason for geographical miss is a change of tumor related atelectasis in the course of radiotherapy. We present the case of a patient with UICC Stage IIIb NSCLC who presented with a large tumor related atelectasis. During definitive radiochemotherapy, the atelectasis resolved, which resulted in a massive tumor shift out of the planning target volume within 2 days. Without close monitoring by cone beam CTs and prompt replanning, this would have led to a geographical miss and relevant underdosage of the tumor. Furthermore, changes in anatomy and pulmonary function during treatment had implications for organs at risk and opened windows for dose escalation. We suggest at least biweekly CBCTs in patients with poststenotic atelectasis to ensure the rapid detection of geographical changes of the target and subsequent intervention if necessary
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