The initial discovery of killer toxin-secreting brewery strains of
(
) in the mid-sixties of the last century marked the beginning of intensive research in the yeast virology field. So far, four ...different
killer toxins (K28, K1, K2, and Klus), encoded by cytoplasmic inherited double-stranded RNA viruses (dsRNA) of the
family, have been identified. Among these, K28 represents the unique example of a yeast viral killer toxin that enters a sensitive cell by receptor-mediated endocytosis to reach its intracellular target(s). This review summarizes and discusses the most recent advances and current knowledge on yeast killer toxin K28, with special emphasis on its endocytosis and intracellular trafficking, pointing towards future directions and open questions in this still timely and fascinating field of killer yeast research.
The International Society for Justice Research (ISJR) aims to provide a platform for interdisciplinary justice scholars who are encouraged to present and exchange their ideas. This exchange has ...yielded a fruitful advance of theoretical and empirically-oriented justice research.This volume substantiates this academic legacy and the research prospects of the ISJR in the field of justice theory and research. Included are themes and topics such as the theory of the justice motive, the mapping of the multifaceted forms of justice (distributive, procedural) and justice in context-bound spheres (e.g. non-humans). It presents a comprehensive "state of the art" overview in the field of justice research theory and it puts forth an agenda for future interdisciplinary and international justice research. It is worth noting that authors in this proposed volume represent ISJR's leading scholarship. Thus, the compilation of their research within a single framework exposes potential readers to high quality academic work that embodies the past, current and future trends of justice research.
In eukaryotic cells, KDEL receptors (KDELRs) facilitate the retrieval of endoplasmic reticulum (ER) luminal proteins from the Golgi compartment back to the ER. Apart from the well-documented ...retention function, recent findings reveal that the cellular KDELRs have more complex roles, e.g. in cell signalling, protein secretion, cell adhesion and tumorigenesis. Furthermore, several studies suggest that a sub-population of KDELRs is located at the cell surface, where they could form and internalize KDELR/cargo clusters after K/HDEL-ligand binding. However, so far it has been unclear whether there are species- or cell-type-specific differences in KDELR clustering. By comparing ligand-induced KDELR clustering in different mouse and human cell lines via live cell imaging, we show that macrophage cell lines from both species do not develop any clusters. Using RT-qPCR experiments and numerical analysis, we address the role of KDELR expression as well as endocytosis and exocytosis rates on the receptor clustering at the plasma membrane and discuss how the efficiency of directed transport to preferred docking sites on the membrane influences the exponent of the power-law distribution of the cluster size.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tumour-infiltrating lymphocytes (TILs) are associated with improved survival in several epithelial cancers. The two chemokines CXCL9 and CXCL10 facilitate chemotactic recruitment of TILs, and their ...intratumoral accumulation is a conceivable way to improve TIL-dependent immune intervention in cancer. However, the prognostic impact of CXCL9 and CXCL10 in high-grade serous ovarian cancer (HGSC) is largely unknown.
One hundred and eighty four cases of HGSC were immunohistochemically analyzed for CXCL9, CXCL10. TILs were assessed using CD3, CD56 and FOXP3 staining. Chemokine regulation was investigated using the ovarian cancer cell lines OV-MZ-6 and SKOV-3.
High expression of CXCL9 and CXCL10 was associated with an approximately doubled overall survival (n=70, CXCL9: HR 0.41; P=0.006; CXCL10: HR 0.46; P=0.010) which was confirmed in an independent validation set (n=114; CXCL9: HR 0.60; P=0.019; CXCL10: HR 0.52; P=0.005). Expression of CXCR3 ligands significantly correlated with TILs. In human ovarian cancer cell lines the cyclooxygenase (COX) metabolite Prostaglandin E2 was identified as negative regulator of chemokine secretion, whereas COX inhibition by indomethacin significantly upregulated CXCL9 and CXCL10. In contrast, celecoxib, the only COX inhibitor prospectively evaluated for therapy of ovarian cancer, suppressed NF-κB activation and inhibited chemokine release.
Our results support the notion that CXCL9 and CXCL10 exert tumour-suppressive function by TIL recruitment in human ovarian cancer. COX inhibition by indomethacin, not by celecoxib, may be a promising approach to concomitantly improve immunotherapies.
Urokinase plasminogen activator (uPA) is an extracellular matrix-degrading protease involved in cancer invasion and metastasis, interacting with plasminogen activator inhibitor-1 (PAI-1), which was ...originally identified as a blood-derived endogenous fast-acting inhibitor of uPA. At concentrations found in tumor tissue, however, both PAI-1 and uPA promote tumor progression and metastasis. Consistent with the causative role of uPA and PAI-1 in cancer dissemination, several retrospective and prospective studies have shown that elevated levels of uPA and PAI-1 in breast tumor tissue are statistically independent and potent predictors of poor patient outcome, including adverse outcome in the subset of breast cancer patients with lymph node-negative disease. In addition to being prognostic, high levels of uPA and PAI-1 have been shown to predict benefit from adjuvant chemotherapy in patients with early breast cancer. The unique clinical utility of uPA/PAI-1 as prognostic biomarkers in lymph node-negative breast cancer has been confirmed in two independent level-of-evidence-1 studies (that is, in a randomized prospective clinical trial in which the biomarker evaluation was the primary purpose of the trial and in a pooled analysis of individual data from retrospective and prospective studies). Thus, uPA and PAI-1 are among the best validated prognostic biomarkers currently available for lymph node-negative breast cancer, their main utility being the identification of lymph node-negative patients who have HER-2-negative tumors and who can be safely spared the toxicity and costs of adjuvant chemotherapy. Recently, a phase II clinical trial using the low-molecular-weight uPA inhibitor WX-671 reported activity in metastatic breast cancer.
Structural approaches to personality have brought about considerable progress in description and prediction of interindividual differences in thoughts, feelings, and behavior. However, in order to ...move towards personality psychology as an explanatory science, we argue that structural, process-oriented and developmental approaches to personality have to be integrated. We summarize the main propositions of a theoretical framework published in a target article in the European Journal of Personality (Baumert et al., 2017a), and highlight the resulting challenges for future personality research.
In the present research, the authors investigated how individual differences in working memory capacity moderate the relative influence of automatic versus controlled precursors on self-regulatory ...behavior. In 2 studies, on sexual interest behavior (Study 1) and the consumption of tempting food (Study 2), automatic attitudes toward the temptation of interest had a stronger influence on behavior for individuals who scored low rather than high in working memory capacity. Analogous results emerged in Study 3 on anger expression in a provoking situation when a measure of the automatic personality trait of angriness was employed. Conversely, controlled dispositions such as explicit attitudes (Study 1) and self-regulatory goals (Studies 2 and 3) were more effective in guiding behavior for participants who scored high rather than low in working memory capacity. Taken together, these results demonstrate the importance of working memory capacity for everyday self-regulation and suggest an individual differences perspective on dual-process or dual-system theories of human behavior.
Since the discovery of toxin-secreting killer yeasts more than 40 years ago, research into this phenomenon has provided insights into eukaryotic cell biology and virus-host-cell interactions. This ...review focuses on the most recent advances in our understanding of the basic biology of virus-carrying killer yeasts, in particular the toxin-encoding killer viruses, and the intracellular processing, maturation and toxicity of the viral protein toxins. The strategy of using eukaryotic viral toxins to effectively penetrate and eventually kill a eukaryotic target cell will be discussed, and the cellular mechanisms of self-defence and protective immunity will also be addressed.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anger, indignation, guilt, rumination, victim compensation, and perpetrator punishment are considered primary responses associated with justice sensitivity (JS). However, injustice and high JS may ...predispose to further responses. We had
N
= 293 adults rate their JS, 17 potential responses toward 12 unjust scenarios from the victim’s, observer’s, beneficiary’s, and perpetrator’s perspectives, and several control variables. Unjust situations generally elicited many affective, cognitive, and behavioral responses. JS generally predisposed to strong affective responses toward injustice, including sadness, pity, disappointment, and helplessness. It impaired trivialization, victim-blaming, or justification, which may otherwise help cope with injustice. It predisposed to conflict solutions and victim compensation. Particularly victim and beneficiary JS had stronger effects in unjust situations from the corresponding perspective. These findings add to a better understanding of the main and interaction effects of unjust situations from different perspectives and the JS facets, differences between the JS facets, as well as the links between JS and behavior and well-being.
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