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Copyright of Yegah Musicology Journal / Yegah Müzikoloji Dergisi is the property of International Yegah Music Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Autophagy refers to a set of degradative mechanisms whereby cytoplasmic contents are targeted to the lysosome. This is best described for macroautophagy, where a double-membrane compartment (autophagosome) is generated to engulf cytoplasmic contents. Autophagosomes are decorated with ubiquitin-like ATG8 molecules (ATG8s), which are recruited through covalent lipidation, catalysed by the E3-ligase-like ATG16L1 complex. LC3 proteins are ATG8 family members that are often used as a marker for autophagosomes. In contrast to canonical macroautophagy, conjugation of ATG8s to single membranes (CASM) describes a group of non-canonical autophagy processes in which ATG8s are targeted to pre-existing single-membrane compartments. CASM occurs in response to disrupted intracellular pH gradients, when the V-ATPase proton pump recruits ATG16L1 in a process called V-ATPase–ATG16L1-induced LC3 lipidation (VAIL). Recent work has demonstrated a parallel, alternative axis for CASM induction, triggered when the membrane recruitment factor TECPR1 recognises sphingomyelin exposed on the cytosolic face of a membrane and forms an alternative E3-ligase-like complex. This sphingomyelin–TECPR1-induced LC3 lipidation (STIL) is independent of the V-ATPase and ATG16L1. In light of these discoveries, this Cell Science at a Glance article summarises these two mechanisms of CASM to highlight how they differ from canonical macroautophagy, and from each other. [ABSTRACT FROM AUTHOR]

Proliferative epithelial lesions in the fallopian tubes may be found incidentally during the microscopic examination of salpingectomy specimens. Recent evidence has clearly implicated the changes in the mucosa of the fimbrial end of the fallopian tube in its pathogenesis of high-grade serous carcinoma (HGSC). These lesions include serous tubular intraepithelial carcinoma (STIC), serous tubular intraepithelial lesion, p53 signature, and secretory cell outgrowth (SCOUT). STIC displays stratification of epithelium, hyperchromatic nuclei, increased mitotic figures, and prominent nucleoli. Immunohistochemistry staining shows aberrant p53 staining and a high Ki-67 index of >10%. Aberrant p53 expression can be either diffuse strong positivity or absent immunostaining due to non-sense mutations. The lesions which have a benign appearance with focal changes of atypia, low proliferative index, and do not satisfy the criteria of STIC on immunohistochemistry are labeled as serous tubular intraepithelial lesions.

Objective: To study effect of STIL gene on proliferation and apoptosis of cervical cancer cells and its mechanism. Methods: Expressions of STIL mRNA and STIL protein in cervical cancer tissues, adjacent tissues, cervical cancer cell lines HeLa, SiHa, caski and human normal cervical epithelial cells HUCEC were calculated by RT-qPCR and Western blot. HeLa cells were divided into control （NC） group, si-NC group, si-STIL group, si-STIL+IL-6 group. CCK-8 and plate cloning assay were utilized to detect cell proliferation and cloning ability, and flow cytometry was used to analyze cell apoptosis rate. Western blot was used to detect IL-6, IL-6R and p-STAT3 proteins levels. sh-STIL stably transfected HeLa cells were subcutaneously inoculated into back of nude mice to investigate effect of inhibiting STIL expression on tumor formation. Results: STIL mRNA and protein expressions in cervical cancer tissues were significantly higher than adjacent tissues （P<0.05）. STIL mRNA and protein expressions in HeLa, SiHa, and caski cells were significantly higher than HUCEC cells （P<0.05）. Compared with si-NC group, cell absorbance, number of clones, and protein levels of IL-6, IL-6R and p-STAT3 in si-STIL group were significantly reduced （P<0.05）, and apoptosis rate was significantly increased （P<0.05）. Compared with si-STIL group, cell absorbance, number of clones and protein levels of IL-6, IL-6R and p-STAT3 in si-STIL+IL-6 group were significantly increased （P<0.05）, and apoptotic rate was significantly reduced （P<0.05）. Inhibiting STIL significantly inhibited tumor growth in vivo （P<0.05）. Conclusion: STIL gene expression is up-regulated in cervical cancer, and inhibiting STIL can inhibit proliferation and induce apoptosis of cervical cancer cells by inhibiting IL-6/STAT3 pathway. [ABSTRACT FROM AUTHOR]

Background: STIL is an important cell cycle-regulating protein specifically recruited to the mitotic centrosome to promote the replication of centrioles in dividing cells. However, the potential role of STIL in the regulation of the biological functions of triple-negative breast cancer remains still unclear. Methods: We screened for differentially expressed STIL in the Cancer Genome Atlas database. The expression of STIL protein in 10 pairs of breast cancer tissues and adjacent normal tissues was further assessed by western blotting. Functionally, the knockdown and overexpression of STIL have been used to explore the effects of STIL on breast cancer cell proliferation, migration, and invasion. Mechanistically, RNA-seq, dual-luciferase reporter assay, chromatin immunoprecipitation assay, mass spectrometry, immunoprecipitation assay, and DNA pull-down assay were performed. Results: Breast cancer tissues and cells have higher STIL expression than normal tissues and cells. STIL knockdown impairs breast cancer cell growth, migration, and invasion, whereas STIL overexpression accelerates these processes. STIL promotes breast cancer progression by regulating FANCD2 expression, and exploration of its molecular mechanism demonstrated that STIL interacts with KLF16 to regulate the expression of FANCD2. Conclusions: Collectively, our findings identified STIL as a critical promoter of breast cancer progression that interacts with KLF16 to regulate Fanconi anemia pathway protein FANCD2. In summary, STIL is a potential novel biomarker and therapeutic target for breast cancer.

Copyright of Post Scriptum - Casopis za Obrazovanje, Nauku i Kulturu is the property of University of Bihac, Faculty of Education and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Social Sciences & Humanities Studies / Društvene i Humanističke Studije (DHS) is the property of Faculty of Humanities & Social Sciences, University of Tuzla and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Centrioles are microtubule-based cylindrical ultrastructures characterized by their definite size and robustness. The molecular capping protein, CPAP (also known as CENPJ) engages its N-terminal region with the centriole microtubules to regulate their length. Nevertheless, the conserved C-terminal glycine-rich G-box of CPAP, which interacts with the centriole inner cartwheel protein STIL, is frequently mutated in primary microcephaly (MCPH) patients. Here, we show that two different MCPH-associated variants, E1235V and D1196N in the CPAP G-box, affect distinct functions at centrioles. The E1235V mutation reduces CPAP centriole recruitment and causes overly long centrioles. The D1196N mutation increases centriole numbers without affecting centriole localization. Both mutations prevent binding to STIL, which controls centriole duplication. Our work highlights the involvement of an alternative CEP152-dependent route for CPAP centriole localization. Molecular dynamics simulations suggest that E1235V leads to an increase in G-box flexibility, which could have implications on its molecular interactions. Collectively, we demonstrate that a CPAP region outside the microtubule-interacting domains influences centriole number and length, which translates to spindle defects and reduced cell viability. Our work provides new insights into the molecular causes of primary microcephaly. [ABSTRACT FROM AUTHOR]

Coiled-coil domains (CCDs) play key roles in regulating both healthy cellular processes and the pathogenesis of various diseases by controlling protein self-association and protein–protein interactions. Here, we probe the mechanism of oligomerization of a peptide representing the CCD of the STIL protein, a tetrameric multi-domain protein that is over-expressed in several cancers and associated with metastatic spread. STIL tetramerization is mediated both by an intrinsically disordered domain (STIL400–700) and a structured CCD (STIL CCD718–749). Disrupting STIL oligomerization via the CCD inhibits its activity in vivo. We describe a comprehensive biophysical and structural characterization of the concentration-dependent oligomerization of STIL CCD peptide. We combine analytical ultracentrifugation, fluorescence and circular dichroism spectroscopy to probe the STIL CCD peptide assembly in solution and determine dissociation constants of both the dimerization, (KD = 8 ± 2 µM) and tetramerization (KD = 68 ± 2 µM) of the WT STIL CCD peptide. The higher-order oligomers result in increased thermal stability and cooperativity of association. We suggest that this complex oligomerization mechanism regulates the activated levels of STIL in the cell and during centriole duplication. In addition, we present X-ray crystal structures for the CCD containing destabilising (L736E) and stabilising (Q729L) mutations, which reveal dimeric and tetrameric antiparallel coiled-coil structures, respectively. Overall, this study offers a basis for understanding the structural molecular biology of the STIL protein, and how it might be targeted to discover anti-cancer reagents. [ABSTRACT FROM AUTHOR]

Abstract Background The primary cilia (PC) is a microtubule-based and nonmotile organelle which protrudes from the surface of almost all mammalian cells. At present, PC has been found to be a deficiency or loss in multiple cancers. Restoring PC could be a novel targeting therapy strategy. Our research showed that PC was reduced in human bladder cancer (BLCA) cells, and PC deficiency promotes cell proliferation. However, the concrete mechanisms remain unknown. SCL/TAL1 interrupting locus (STIL), a PC-related protein, was screened in our previous study and could influence the cell cycle by regulating PC in tumor cells. In this study, we aimed to elucidate the function of STIL for PC to explore the underlying mechanism of PC in BLCA. Methods Public database analysis, western blot, and enzyme-linked immunosorbent assay (ELISA) were used to screen genes and explore gene expression alteration. Immunofluorescence and western blot were utilized to investigate PC. Wound healing assay, clone formation assay, and CCK-8 assay were used to explore cell migration, growth, and proliferation. The co-immunoprecipitation and western blot were employed to reveal the interaction of STIL and AURKA. Results We found that high STIL expression is correlated with poor outcomes of BLCA patients. Further analysis revealed that STIL overexpression could inhibit PC formation, activate SHH signaling pathways, and promote cell proliferation. In contrast, STIL-knockdown could promote PC formation, inactivate SHH signaling, and inhibit cell proliferation. Furthermore, we found that the regulatory functions of STIL for PC depend on AURKA. STIL could influence proteasome activity and maintain AURKA stabilization. AURKA-knockdown could reverse PC deficiency caused by STIL overexpression for PC in BLCA cells. We observed that co-knockdown in STIL and AURKA significantly enhanced PC assembly. Conclusion In summary, our result provides a potential therapy target for BLCA based on the restoration of PC.

Background: The primary cilia (PC) is a microtubule-based and nonmotile organelle which protrudes from the surface of almost all mammalian cells. At present, PC has been found to be a deficiency or loss in multiple cancers. Restoring PC could be a novel targeting therapy strategy. Our research showed that PC was reduced in human bladder cancer (BLCA) cells, and PC deficiency promotes cell proliferation. However, the concrete mechanisms remain unknown. SCL/TAL1 interrupting locus (STIL), a PC-related protein, was screened in our previous study and could influence the cell cycle by regulating PC in tumor cells. In this study, we aimed to elucidate the function of STIL for PC to explore the underlying mechanism of PC in BLCA. Methods: Public database analysis, western blot, and enzyme-linked immunosorbent assay (ELISA) were used to screen genes and explore gene expression alteration. Immunofluorescence and western blot were utilized to investigate PC. Wound healing assay, clone formation assay, and CCK-8 assay were used to explore cell migration, growth, and proliferation. The co-immunoprecipitation and western blot were employed to reveal the interaction of STIL and AURKA. Results: We found that high STIL expression is correlated with poor outcomes of BLCA patients. Further analysis revealed that STIL overexpression could inhibit PC formation, activate SHH signaling pathways, and promote cell proliferation. In contrast, STIL-knockdown could promote PC formation, inactivate SHH signaling, and inhibit cell proliferation. Furthermore, we found that the regulatory functions of STIL for PC depend on AURKA. STIL could influence proteasome activity and maintain AURKA stabilization. AURKA-knockdown could reverse PC deficiency caused by STIL overexpression for PC in BLCA cells. We observed that co-knockdown in STIL and AURKA significantly enhanced PC assembly. Conclusion: In summary, our result provides a potential therapy target for BLCA based on the restoration of PC. [ABSTRACT FROM AUTHOR]

Das translatorische Handeln literarischer Übersetzer rückt immer mehr in den Vordergrund moderner translationswissenschaftlicher Studien. Am Beispiel des Übersetzers Curt Meyer-Clason, der insgesamt über 150 Romane und unzählige Gedichte aus dem Englischen, Französischen, Portugiesischen und Spanischen übersetzte und als einer der größten Kulturvermittler Lateinamerikas des 20. Jahrhunderts gilt, soll eine mögliche Vorgehensweise zur Rekonstruktion seiner (impliziten) Übersetzungstheorie vorgestellt werden. Für diesen Zweck werden die Peritexte und Fachzeitschriftenbeiträge des Übersetzers ausgewertet. Die theoretischen Äußerungen zum Thema Übersetzen sollen anderen Übersetzungstheoretikern gegenübergestellt werden, um Meyer-Clason bestimmten Übersetzungsparadigmen zuordnen zu können. In der Übersetzungskritik wird auf einige Übersetzungsstrategien des Übersetzers eingegangen, um zu überprüfen, ob Diskrepanzen zwischen den theoretischen Ansprüchen und dem praktischen Übersetzen festzustellen sind. Für eine gerechte, akteursorientierte Übersetzungskritik spielt – neben den theoretischen Ansprüchen des Translators – auch seine Topobiografie und die damit einhergehende Individualität des Übersetzers eine wichtige Rolle. Am Beispiel Curt Meyer-Clasons soll exemplarisch dargestellt werden, wie bedeutend der biobibliografische Hintergrund für die Übersetzer- und Übersetzungsforschung ist.

Recent findings suggest that high-grade serous ovarian cancer can originate in the fallopian tube. Not only has that made the identification of precursor lesions pivotal in early detection and prevention of these cancers, prophylactic salpingectomy alongside hysterectomy for benign indications has been increasingly proposed as well. The present prospective single-center study included 273 women who underwent opportunistic salpingectomy alongside laparoscopic supracervical hysterectomy. Uterine and tubal histopathological results as well as intra- and postoperative complications were evaluated. The complication rate was 3.3%, of which none were caused by salpingectomy. Uterine histopathology diagnosed 181 patients (66.8%) with uterine myomas, 60 patients (22.1%) with adenomyosis, 29 patients (10.7%) with adenomyomatosis, and, 1 patient (0.4%) without pathological abnormality. p53 signatures were detected in 221 right fallopian tubes (80.9%) and in 229 left tubes (83.9%). In total, 8 patients showed bilateral STIL (2.9%), whereas in 1 patient (0.4%) STIL was detected in the left tube only. No STIC were detected. Laparoscopic opportunistic salpingectomy is demonstrated to be both safe and feasible. It appears to be promising to reduce the risk for ovarian cancer, yet more studies are needed to undoubtedly confirm this. [ABSTRACT FROM AUTHOR]

Copyright of Filozofija i Drustvo is the property of University of Belgrade, Institute for Philosophy & Social Theory and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Currently; there are no reports on the role of STIL in bladder cancer. Using public databases; we observed that STIL is highly expressed in bladder cancer and is closely related to the cell cycle. The results of tumor formation experiments on UMUC3 and T24 bladder cancer cell lines indicate that STIL promotes the growth of bladder cancer cells in vivo and in vitro. Mechanistically, the cell cycle after STIL knockout was arrested in the G0/G1 phase; and cell cycle-related proteins (cyclin D1 and CDK2/4/6) were also reduced. RNA-seq results and immunoblotting experiments confirmed that STIL enhanced the PI3K/AKT/mTOR pathway, resulting in increased c-myc expression which ultimately promoted the occurrence and progression of bladder cancer. Our results suggest that STIL may be a promising potential therapeutic target for bladder cancer. SCL/TAL1 interrupting locus (STIL) regulates centriole replication and causes chromosome instability, which is closely related to malignant tumors. The purpose of our study was to investigate the role of STIL in bladder cancer (BC) tumorigenesis for the first time. The public database indicated that STIL is highly expressed and correlated with the cell cycle in BC. Immunohistochemistry staining showed that STIL expression is significantly elevated in BC tissues compared with paracancer tissues. CRISPR-Cas9 gene editing technology was used to induce BC cells to express STIL-specific sgRNA, revealing a significantly delayed growth rate in STIL knockout BC cells. Moreover, cell cycle arrest in the G0/G1 phase was triggered by decreasing STIL, which led to delayed BC cell growth in vitro and in vivo. Mechanically, STIL knockout inhibited the PI3K/AKT/mTOR pathway and down-regulated the expression of c-myc. Furthermore, SC79 (AKT activating agent) partially reversed the inhibitory effects of STIL knockout on the proliferation and migration of BC cells. In conclusion, STIL enhanced the PI3K/AKT/mTOR pathway, resulting in increased expression of c-myc, ultimately promoting BC occurrence and progression. These results indicate that STIL might be a potential target for BC patients. [ABSTRACT FROM AUTHOR]

Abstract Background Metastasis is the major cause of morbidity and mortality in cancer that involves in multiple steps including epithelial–mesenchymal transition (EMT) process. Centrosome is an organelle that functions as the major microtubule organizing center (MTOC), and centrosome abnormalities are commonly correlated with tumor aggressiveness. However, the conclusive mechanisms indicating specific centrosomal proteins participated in tumor progression and metastasis remain largely unknown. Methods The expression levels of centriolar/centrosomal genes in various types of cancers were first examined by in silico analysis of the data derived from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and European Bioinformatics Institute (EBI) datasets. The expression of STIL (SCL/TAL1-interrupting locus) protein in clinical specimens was further assessed by Immunohistochemistry (IHC) analysis and the oncogenic roles of STIL in tumorigenesis were analyzed using in vitro and in vivo assays, including cell migration, invasion, xenograft tumor formation, and metastasis assays. The transcriptome differences between low- and high-STIL expression cells were analyzed by RNA-seq to uncover candidate genes involved in oncogenic pathways. The quantitative polymerase chain reaction (qPCR) and reporter assays were performed to confirm the results. The chromatin immunoprecipitation (ChIP)-qPCR assay was applied to demonstrate the binding of transcriptional factors to the promoter. Results The expression of STIL shows the most significant increase in lung and various other types of cancers, and is highly associated with patients’ survival rate. Depletion of STIL inhibits tumor growth and metastasis. Interestingly, excess STIL activates the EMT pathway, and subsequently enhances cancer cell migration and invasion. Importantly, we reveal an unexpected role of STIL in tumor metastasis. A subset of STIL translocate into nucleus and associate with FOXM1 (Forkhead box protein M1) to promote tumor metastasis and stemness via FOXM1-mediated downstream target genes. Furthermore, we demonstrate that hypoxia-inducible factor 1α (HIF1α) directly binds to the STIL promoter and upregulates STIL expression under hypoxic condition. Conclusions Our findings indicate that STIL promotes tumor metastasis through the HIF1α-STIL-FOXM1 axis, and highlight the importance of STIL as a promising therapeutic target for lung cancer treatment.

Coiled-coil domains (CCDs) play key roles in regulating both healthy cellular processes and the pathogenesis of various diseases by controlling protein self-association and protein–protein interactions. Here, we probe the mechanism of oligomerization of a peptide representing the CCD of the STIL protein, a tetrameric multi-domain protein that is over-expressed in several cancers and associated with metastatic spread. STIL tetramerization is mediated both by an intrinsically disordered domain (STIL400–700) and a structured CCD (STIL CCD718–749). Disrupting STIL oligomerization via the CCD inhibits its activity in vivo. We describe a comprehensive biophysical and structural characterization of the concentration-dependent oligomerization of STIL CCD peptide. We combine analytical ultracentrifugation, fluorescence and circular dichroism spectroscopy to probe the STIL CCD peptide assembly in solution and determine dissociation constants of both the dimerization, (KD = 8 ± 2 µM) and tetramerization (KD = 68 ± 2 µM) of the WT STIL CCD peptide. The higher-order oligomers result in increased thermal stability and cooperativity of association. We suggest that this complex oligomerization mechanism regulates the activated levels of STIL in the cell and during centriole duplication. In addition, we present X-ray crystal structures for the CCD containing destabilising (L736E) and stabilising (Q729L) mutations, which reveal dimeric and tetrameric antiparallel coiled-coil structures, respectively. Overall, this study offers a basis for understanding the structural molecular biology of the STIL protein, and how it might be targeted to discover anti-cancer reagents.

Öğrenci öğrenme stillerinin çeşitliliğinin yanısıra öğrenmenin yapılandırmacı doğasının artan tanınırlığı ile birlikte öğretmenlerin farklı öğretim stilleri kullanma ihtiyacı vurgulanır iken öğretmenlerin çeşitli öğretim stillerini ve algılaması hakkında çok az şey bilinmektedir. Buna paralel olarak antrenörlerin öğretim stilleri kullanması ve algılaması hakkında çok daha az çalışmanın olduğu görülmektedir. Bu nedenle, bu çalışmada antrenörlerin ve beden eğitimi öğretmenlerinin öğretim stillerini kullanma düzeyleri ve stillere ilişkin değer algılarının, grup, cinsiyet, yaş, eğitim durumları değişkenlerine göre karşılaştırarak incelenmiştir. Edirne merkezde MEM’de çalışan 90 öğretmen ile GSİM’de çalışan 39 antrenör olmak üzere toplam 129 katılımcı, kolayda örneklem yöntemi ile seçilmiş ve gönüllük ilkesine göre katılmışlardır. Bulgulara göre en çok değer verilen stiller, komut ve alıştırma, en az değer verilen stiller ise kendi kendine öğretme ve öğrencinin başlatması olarak sıralanmıştır. En çok kullanılan stiller komut ve alıştırma, en az kullanılan stiller ise kendi kendine öğretme ve öğrencinin başlatması olarak sıralandığı görülmektedir. Stillerin öğrencilere “Eğlenme”, “Öğrenme” ve “Motivasyon” sağlama boyutlarında; motivasyon açısından komut, alıştırma ve eşli çalışma, öğrenme açısından komut, alıştırma ve katılım, eğlence açısından komut, alıştırma ve katılım stillerine en fazla değer verildiği görülmektedir. Bulgular grup, cinsiyet ve yaş değişkenlerine göre stillere ilişkin değer algıları ve kullandıkları öğretim stilleri ortalama puanlarının karşılaştırılması sonuçlarında anlamlı değişikler olduğu görülmüştür. Sonuç olarak, en çok kullanılan ve değer verilen stiller olarak komut ve alıştırma stillerinin seçilmesi, öğretmen ve antrenörün öğrenciler üzerinde kontrolün daha fazla arttırma istekleri, bu stillere yönelten temel sebep olarak görülebilir. Bu nedenle beden eğitimi öğretmenliği ve antrenörlük programında öğrenimlerini sürdüren öğretmen ve antrenör adaylarının öğrenim süreleri boyunca aldıkları farklı derslerde uygulama imkanı bulmaları için fırsatlar verilerek, diğer öğretim stillerinin stratejik kullanım alanlarının keşfetmeleri sağlanarak, deneyim kazanmaları ve mesleki gelişim programlarının bu doğrultuda hazırlanması önerilir.

Copyright of Papers of Hungarian Studies / Hungarologiai Kozlemenyek is the property of Faculty of Philosophy, University of Novi Sad and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Online Journal of Art & Design is the property of Online Journal of Art & Design and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: This study investigated the effect of neoadjuvant chemotherapy (NAC) on stromal tumor-infiltrating lymphocytes (sTILs) and their treatment response. Materials & methods: 115 patients with pre-NAC core biopsies and post-NAC surgical resection specimens were reviewed. Results: There was no significant change between pre- and post-treatment sTILs. Both pre- and post-NAC sTILs were significantly lower in patients with luminal A subtype. An increase in sTILs was observed in 21 (25.9%) patients after NAC, a decrease in 29 (35.8%) and no change in 31 (38.3%; p = 0.07). Pretreatment sTIL density was independent predictor of pathological complete response in multivariate analyses (odds ratio: 1.025, 95% CI: 1.003-1.047; p = 0.023). Conclusion: High sTIL density in core biopsies was independently related to pathological complete response. In addition, ER appears to be the most crucial factor determining the rate of sTIL. [ABSTRACT FROM AUTHOR]

The centrosome plays an essential role in maintaining genetic stability, ciliogenesis and cell polarisation. The core of the centrosome is made up of two centrioles that duplicate precisely once during every cell cycle to generate two centrosomes that are required for bipolar spindle assembly and chromosome segregation. Abundance of centriole proteins at optimal levels and their recruitment to the centrosome are tightly regulated in time and space in order to restrict aberrant duplication of centrioles, a phenomenon that is observed in many cancers. Recent advances have conclusively shown that dedicated ubiquitin ligase‐dependent protein degradation machineries are involved in governing centriole duplication. These studies revealed intricate mechanistic insights into how the ubiquitin ligases target different centriole proteins. In certain cases, a specific ubiquitin ligase targets a number of substrate proteins that co‐regulate centriole assembly, prompting the possibility that substrate‐targeting occurs during formation of the sub‐centriolar structures. There are also instances where a specific centriole duplication protein is targeted by several ubiquitin ligases at different stages of the cell cycle, suggesting synchronised actions. Recent evidence also indicated a direct association of E3 ubiquitin ligase with the centrioles, supporting the notion that substrate‐targeting occurs in the organelle itself. In this review, we highlight these advances by underlining the mechanisms of how different ubiquitin ligase machineries control centriole duplication and discuss our views on their coordination. [ABSTRACT FROM AUTHOR]

In the article, the concept of style in piano education and performance has been investigated in detail, and artists, educators, musicologists, etc. The comments made by The historical development of this concept in different periods is explained in detail. The concept of style has been examined by evaluating the methods and pedagogical attitudes of wellknown piano educators, and based on personal observations and the experiences of these educators, some rules and suggestions necessary for the understanding of style in piano performance are presented at the end of the article. This study, which was carried out in order to master the piano performance, to gain a musical identity and to convey musical thoughts in a professional way, was carried out with the thought of being useful in the field of education. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Language & Literary Studies / Folia Linguistica & Litteraria is the property of Journal of Language & Literary Studies / Folia Linguistica & Litteraria and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background SCL/TAL1 interrupting locus (STIL) is associated with the progression of several tumors; however, the biological role of STIL in osteosarcoma remains poorly understood. Methods In this study, the clinical significance of STIL in osteosarcoma was analyzed by gene chip data recorded in public databases. STIL expression was silenced in osteosarcoma cell lines to observe the effects on proliferation, apoptosis, invasion, and migration. Differentially expressed genes (DEGs) in the osteosarcoma chip were analyzed using The Limma package, and STIL co-expressed genes were obtained via the Pearson correlation coefficient. The potential molecular mechanism of STIL in osteosarcoma was further explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results Osteosarcoma was associated with higher STIL expression compared to the control samples, and the standardized mean difference (SMD) was 1.52. STIL also had a good ability to distinguish osteosarcoma from non-osteosarcoma samples [area under the curve (AUC) = 0.96]. After silencing STIL, osteosarcoma cell proliferation decreased, apoptosis increased, and the migratory and invasion ability decreased. A total of 294 STIL differentially co-expressed genes were screened, and a bioinformatics analysis found that differentially co-expressed genes were primarily enriched in the cell signaling pathways. The protein-protein interaction (PPI) network indicated that the hub differentially co-expressed genes of STIL were CDK1, CCNB2, CDC20, CCNA2, BUB1, and AURKB. Conclusions STIL is associated with osteosarcoma proliferation and invasion, and may be promote the progression of osteosarcoma by regulating the expression of CDK1, CCNB2, CDC20, CCNA2, BUB1 and AURKB.

Background: Metastasis is the major cause of morbidity and mortality in cancer that involves in multiple steps including epithelial–mesenchymal transition (EMT) process. Centrosome is an organelle that functions as the major microtubule organizing center (MTOC), and centrosome abnormalities are commonly correlated with tumor aggressiveness. However, the conclusive mechanisms indicating specific centrosomal proteins participated in tumor progression and metastasis remain largely unknown. Methods: The expression levels of centriolar/centrosomal genes in various types of cancers were first examined by in silico analysis of the data derived from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and European Bioinformatics Institute (EBI) datasets. The expression of STIL (SCL/TAL1-interrupting locus) protein in clinical specimens was further assessed by Immunohistochemistry (IHC) analysis and the oncogenic roles of STIL in tumorigenesis were analyzed using in vitro and in vivo assays, including cell migration, invasion, xenograft tumor formation, and metastasis assays. The transcriptome differences between low- and high-STIL expression cells were analyzed by RNA-seq to uncover candidate genes involved in oncogenic pathways. The quantitative polymerase chain reaction (qPCR) and reporter assays were performed to confirm the results. The chromatin immunoprecipitation (ChIP)-qPCR assay was applied to demonstrate the binding of transcriptional factors to the promoter. Results: The expression of STIL shows the most significant increase in lung and various other types of cancers, and is highly associated with patients' survival rate. Depletion of STIL inhibits tumor growth and metastasis. Interestingly, excess STIL activates the EMT pathway, and subsequently enhances cancer cell migration and invasion. Importantly, we reveal an unexpected role of STIL in tumor metastasis. A subset of STIL translocate into nucleus and associate with FOXM1 (Forkhead box protein M1) to promote tumor metastasis and stemness via FOXM1-mediated downstream target genes. Furthermore, we demonstrate that hypoxia-inducible factor 1α (HIF1α) directly binds to the STIL promoter and upregulates STIL expression under hypoxic condition. Conclusions: Our findings indicate that STIL promotes tumor metastasis through the HIF1α-STIL-FOXM1 axis, and highlight the importance of STIL as a promising therapeutic target for lung cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract Background The H&E stromal tumor-infiltrating lymphocyte (sTIL) score and programmed death ligand 1 (PD-L1) SP142 immunohistochemistry assay are prognostic and predictive in early-stage breast cancer, but are operator-dependent and may have insufficient precision to characterize dynamic changes in sTILs/PD-L1 in the context of clinical research. We illustrate how multiplex immunofluorescence (mIF) combined with statistical modeling can be used to precisely estimate dynamic changes in sTIL score, PD-L1 expression, and other immune variables from a single paraffin-embedded slide, thus enabling comprehensive characterization of activity of novel immunotherapy agents. Methods Serial tissue was obtained from a recent clinical trial evaluating loco-regional cytokine delivery as a strategy to promote immune cell infiltration and activation in breast tumors. Pre-treatment biopsies and post-treatment tumor resections were analyzed by mIF (PerkinElmer Vectra) using an antibody panel that characterized tumor cells (cytokeratin-positive), immune cells (CD3, CD8, CD163, FoxP3), and PD-L1 expression. mIF estimates of sTIL score and PD-L1 expression were compared to the H&E/SP142 clinical assays. Hierarchical linear modeling was utilized to compare pre- and post-treatment immune cell expression, account for correlation of time-dependent measurement, variation across high-powered magnification views within each subject, and variation between subjects. Simulation methods (Monte Carlo, bootstrapping) were used to evaluate the impact of model and tissue sample size on statistical power. Results mIF estimates of sTIL and PD-L1 expression were strongly correlated with their respective clinical assays (p

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Copyright of Studia Universitatis Babes-Bolyai, Philologia is the property of Babes-Bolyai University, Cluj-Napoca, Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

En ny tid krever en ny stil. Slik lød modernismens kanskje viktigste tese, skrevet i gull over inngangen til Joseph Maria Olbrichs Secesjonsbygning i Wien. Men stil har ikke alltid hatt med tidsmessighet å gjøre. Parallelt med ideen om stil som tidsåndens selvuttrykk, løper et annet stilbegrep som fungerte, ikke som epokesignatur, men som en tidsmaskin som kunne forbinde her og nå med andre tider og steder. Hele verdener kunne forflyttes ved hjelp av stil: Den tyske 1700-tallsskribenten C.C. Hirschfeld kalte det «stilens verdensborgerskap». Dette essayet undersøker 1800-tallets utidsmessige stilbegrep i norsk og tysk arkitekturtenkning.

SCL/TAL1 Interrupting locus (STIL) is a ciliary-related gene involved in regulating the cell cycle and duplication of centrioles in dividing cells. STIL has been found disordered in multiple cancers and driven carcinogenesis. However, the molecular mechanisms and biological functions of STIL in cancers remain ambiguous. Here, we systematically analyzed the genetic alterations, molecular mechanisms, and clinical relevance of STIL across >10,000 samples representing 33 cancer types in The Cancer Genome Atlas (TCGA) dataset. We found that STIL expression is up-regulated in most cancer types compared with their adjacent normal tissues. The expression dysregulation of STIL was affected by copy number variation, mutation, and DNA methylation. High STIL expression was associated with worse outcomes and promoted the progression of cancers. Gene Ontology (GO) enrichment analysis and Gene Set Variation Analysis (GSVA) further revealed that STIL is involved in cell cycle progression, Mitotic spindle, G2M checkpoint, and E2F targets pathways across cancer types. STIL expression was negatively correlated with multiple genes taking part in ciliogenesis and was positively correlated with several genes which participated with centrosomal duplication or cilia degradation. Moreover, STIL silencing could promote primary cilia formation and inhibit cell cycle protein expression in prostate and kidney cancer cell lines. The phenotype and protein expression alteration due to STIL silencing could be reversed by IFT88 silencing in cancer cells. These results revealed that STIL could regulate the cell cycle through primary cilia in tumor cells. In summary, our results revealed the importance of STIL in cancers. Targeting STIL might be a novel therapeutic approach for cancers.