Mediamusic (E-Journal)
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Biological functions of therapy-induced senescence in cancer
No full textTherapy-induced cellular senescence is a state of stable growth arrest induced by common cancer treatments such as chemotherapy and radiation. In an oncogenic context, therapy-induced senescence can have different consequences. By blocking cellular proliferation and by facilitating immune cell infiltration, it functions as tumor suppressive mechanism. By fueling the proliferation of bystander cells and facilitating metastasis, it acts as a tumor promoting factor. This dual role is mainly attributed to the differential expression and secretion of a set of pro-inflammatory cytokines and tissue remodeling factors, collectively known as the Senescence-Associated Secretory Phenotype (SASP). Here, we describe cell-autonomous and non-cell-autonomous mechanisms that senescent cells activate in response to chemotherapy and radiation leading to tumor suppression and tumor promotion. We present the current state of knowledge on the stimuli that affect the activation of these opposing mechanisms and the effect of senescent cells on their micro-environment eg. by regulating the functions of immune cells in tumor clearance as well as strategies to eliminate senescent tumor cells before exerting their deleterious side-effects.</p
« Sans adieu ». Andries Bonger – Odilon Redon, correspondance 1894 – 1916
No full textCritical edition of a major correspondence (1894-1914) between Odilon Redon and one of his foremost collectors, the Dutch insurance broker Andries Bonger. The latter’s important collection of works by Redon and Emile Bernard is now in the Collectie Nederland, mostly in the Van Gogh Museum. The importance of this correspondence is exceptional, not only due to its scope, but also because of the formal and intellectual quality of the exchange, because its documents the life, art and reflections of one of the major French artists of the turn of the century and of a foremost collector of modern art in the Netherlands, as well as the artistic, cultural and social life of which they were a part. The aesthetic, intellectual and moral affinity between the two men, the many roles assumed by Bonger in relation to Redon—agent, critic, and to some extent historian, as well as collector and patron—also make this correspondence a milestone in the history of artist-patron relationships in the late nineteenth and early twentieth centuries. Moreover, since Redon’s precociously Symbolist art met at first with strong resistance (except for small literary circles) in France, but found a crucial support in the burgeoning international network of “independent” art in Belgium and the Netherlands, before it extended to Germany, Switzerland and the United States, these letters also illuminate the geography of artistic exchange and circulation within Europe at this critical juncture.<br/
Effects of canagliflozin on myocardial infarction:a post hoc analysis of the CANVAS Program and CREDENCE trial
No full textAIMS: Given the benefits of sodium glucose co-transporter 2 inhibition (SGLT2i) in protecting against heart failure in diabetic patients, we sought to explore the potential impact of SGLT2i on the clinical features of patients presenting with myocardial infarction (MI) through a post-hoc analysis of CANVAS Program and CREDENCE trial.METHODS AND RESULTS: Individuals with type 2 diabetes and history or high risk of cardiovascular disease (CANVAS Program) or type 2 diabetes and chronic kidney disease (CREDENCE) were included. The intervention was Canagliflozin 100 or 300 mg (combined in the analysis) or placebo. MI events were adjudicated as ST-elevation myocardial infarction (STEMI), non-STEMI as well as type 1 MI or type 2 MI. 421 first MI events in the CANVAS Program and 178 first MI events in the CREDENCE trial were recorded (83 fatal, 128 STEMI, 431 non-STEMI, and 40 unknown). No benefit of canagliflozin compared with placebo on time to first MI event was observed (HR 0.89; 95% CI 0.75, 1.05). Canagliflozin was associated with lower risk for non-STEMI (HR 0.78; 95% CI 0.65, 0.95) but suggested a possible increase in STEMI (HR 1.55; 95% CI 1.06, 2.27), with no difference in risk of type 1 or type 2 MI. There was no change in fatal MI (HR 1.22, 95% CI 0.78, 1.93).CONCLUSIONS: Canagliflozin was not associated with a reduction in overall MI in the pooled CANVAS Program and CREDENCE trial population. The possible differential effect on STEMI and Non-STEMI observed in the CANVAS cohort warrants further investigation.</p
Reliability assessment of hyperspectral imaging with the HyperView (TM) system for lower extremity superficial tissue oxygenation in young healthy volunteers
No full textPURPOSE: Hyperspectral imaging (HSI) is a noninvasive spectroscopy technique for determining superficial tissue oxygenation. The HyperView™ system is a hand-held camera that enables perfusion image acquisition. The evaluation of superficial tissue oxygenation is warranted in the evaluation of patients with peripheral arterial disease. The aim was to determine the reliability of repeated HSI measurements.METHODS: In this prospective cohort study, HSI was performed on 50 healthy volunteers with a mean age of 26.4 ± 2.5 years, at the lower extremity. Two independent observers performed HSI during two subsequent measurement sessions. Short term test-retest reliability and intra- and inter-observer reliability were determined, and generalizability and decision studies were performed. Transcutaneous oxygen pressure (TcPO2) measurements were also performed.RESULTS: The short term test-retest reliability was good for the HSI values determined at the lower extremity, ranging from 0.72 to 0.90. Intra- and inter-observer reliability determined at different days were poor to moderate for both HSI (0.24 to 0.71 and 0.30 to 0.58, respectively) and TcPO2 (0.54 and 0.56, and 0.51 and 0.31, respectively). Reliability can be increased to >0.75 by averaging two measurements on different days.CONCLUSION: This study showed good short term test-retest reliability for HSI measurements, however low intra- and inter-observer reliability was observed for tissue oxygenation measurements with both HSI and TcPO2 performed at separate days in young healthy volunteers. Reliability of HSI can be improved when determined as a mean of two measurements taken on different days.</p
The surface of lipid droplets constitutes a barrier for endoplasmic reticulum-resident integral membrane proteins
No full textLipid droplets (LDs) are globular subcellular structures that store neutral lipids. LDs are closely associated with the endoplasmic reticulum (ER) and are limited by a phospholipid monolayer harboring a specific set of proteins. Most of these proteins associate with LDs through either an amphipathic helix or a membrane-embedded hairpin motif. Here, we address the question of whether integral membrane proteins can localize to the surface of LDs. To test this, we fused perilipin 3 (PLIN3), a mammalian LD-targeted protein, to ER-resident proteins. The resulting fusion proteins localized to the periphery of LDs in both yeast and mammalian cells. This peripheral LD localization of the fusion proteins, however, was due to a redistribution of the ER around LDs, as revealed by bimolecular fluorescence complementation between ER- and LD-localized partners. A LD-tethering function of PLIN3-containing membrane proteins was confirmed by fusing PLIN3 to the cytoplasmic domain of an outer mitochondrial membrane protein, OM14. Expression of OM14-PLIN3 induced a close apposition between LDs and mitochondria. These data indicate that the ER-LD junction constitutes a barrier for ER-resident integral membrane proteins.</p
Education increases decision-rule use:An investigation of education and incentives to improve decision making
No full textRobust scientific evidence shows that human performance predictions are more valid when information is combined mechanically (with a decision rule) rather than holistically (in the decision-maker’s mind). Yet, information is often combined holistically in practice. One reason is that decision makers lack knowledge of evidence-based decision making. In a performance prediction task, we tested whether watching an educational video on evidence-based decision making increased decision-makers’ use of a decision rule and their prediction accuracy immediately after the manipulation and a month later. Furthermore, we manipulated whether participants earned incentives for accurate predictions. Existing research showed that incentives decrease decision-rule use and prediction accuracy. We hypothesized that this is the case for decision makers who did not receive educational information about evidence-based decision making, but that incentives increase decision-rule use and prediction accuracy for participants who received educational information. Our results showed that educational information increased decision-rule use. This resulted in increased prediction accuracy, but only immediately after receiving the educational information. In contrast to the existing literature, incentives slightly increased decision-rule use. We did not find evidence that this effect was larger for educated participants. Providing decision makers with educational information may be effective to increase decision-rule use in practice
Autophagy induction during stem cell activation plays a key role in salivary gland self-renewal
No full textRelatively quiescent tissues like salivary glands (SGs) respond to stimuli such as injury to expand, replace and regenerate. Resident stem/progenitor cells are key in this process because, upon activation, they possess the ability to self-renew. Macroautophagy/autophagy contributes to and regulates differentiation in adult tissues, but an important question is whether this pathway promotes stem cell self-renewal in tissues. We took advantage of a 3D organoid system that allows assessing the self-renewal of mouse SGs stem cells (SGSCs). We found that autophagy in dormant SGSCs has slower flux than self-renewing SGSCs. Importantly, autophagy enhancement upon SGSCs activation is a self-renewal feature in 3D organoid cultures and SGs regenerating in vivo. Accordingly, autophagy ablation in SGSCs inhibits self-renewal whereas pharmacological stimulation promotes self-renewal of mouse and human SGSCs. Thus, autophagy is a key pathway for self-renewal activation in low proliferative adult tissues, and its pharmacological manipulation has the potential to promote tissue regeneration.</p
Medieval iron and charcoal production in the Veluwe region (Central Netherlands). New investigations on a production landscape in the woodlands of 't Asselt near the village of Rheden.
No full textMedieval iron and charcoal production in the Veluwe region - Recent research on the iron production landscape in the coppice wood of ‘t Asselt near Rheden (Southeastern Veluwe) Between the seventh and twelfth century ad large-scale iron production took place in the Veluwe region (Central Netherlands) based on the extraction of iron-rich loam concretions in the regional ice-pushed ridges.This iron production required large amounts of charcoal which were produced by the large-scale burning of semi-natural and/or coppice woods. There is palaeobotanical evidence that the woodland vegetation of the Veluwe diminished by two-thirds in this medieval period, partly because of medieval woodland reclamations, partly because of charcoal-burning. A master thesis project revealed the existence of an extensive and largely untouched iron production landscape in the coppice wood of ‘t Asselt (Southeastern Veluwe). Based on ceramics from the eighth-twelfth century, historical-geographical relics as well as w ritten evidence this early and high medieval landscape layer seems rather complete and untouched, which makes it a very promising site for further archaeological research on medieval iron production landscapes.Between the seventh and twelfth century AD a large-scale iron production took place in the Veluwe region (Central Netherlands) based on the extraction of iron-rich loam concretions in the regional ice-pushed ridges. This iron production required large amounts of charcoal which were produced by the large-scale burning of semi-natural and/or coppice woods. There is palaeobotanical evidence that the woodland vegetation of the Veluwe diminished by two-third in this medieval period, partly because of medieval woodland reclamations, partly because of charcoal-burning. A master thesis project revealed the existence of an extensive and largely untouched iron production landscape in the coppice wood of ‘t Asselt (Southeastern Veluwe). Based on ceramics from the 8th-12th century, historical-geographical relics as well as written evidence this early and high medieval landscape layer seems rather complete and untouched, which makes it a very promising site for further archaeological research on medieval iron production landscapes
Counterproductive Work Behaviors and Work Climate:The Role of an Ethically Focused Management Control System and Peers’ Self-Focused Behavior
No full textThe importance of curtailing undesirable behaviors and, ultimately, self-focused work climates in organizations is undeniable. This study examines how management control systems (MCSs), as a crucial part of a firm’s formal ethical infrastructure, can contribute to this objective. We conceptualize an ethically focused MCS as one that communicates ethical values and motivates employees to act accordingly. Our study is based on data from a sample of 120 department managers from 120 different firms. We show that department managers’ perceptions of the extent to which the MCS imposed on them is ethically focused are associated with a reduction in their counterproductive work behaviors (CWBs). We also examine department managers’ perceptions of peer managers’ self-focused behaviors, as a core part of a firm’s informal ethical infrastructure and find that peers’ behaviors are not associated with an increase in CWBs of the department manager. However, we find some evidence that the negative association between an ethically focused MCS and managers’ CWBs is limited when peers act in ways that are more self-focused. Finally, we find that CWBs of department managers are not only relevant in and of themselves, but they translate into more self-focused behaviors of department employees (as manifested in their work climates). Overall, this study suggests that, while including and emphasizing ethical content in the MCS is associated with less CWB and, in turn, with a work climate less focused on self, peer managers’ behaviors are also seemingly important