E3 Ligase Activity of XIAP RING Domain Is Required for XIAP-Mediated Cancer Cell Migration, but Not for Its RhoGDI Binding Activity

Although an increased expression level of XIAP is associated with cancer cell metastasis, the underlying molecular mechanisms remain largely unexplored. To verify the specific structural basis of XIAP for regulation of cancer cell migration, we introduced different XIAP domains into XIAP−/− HCT116 cells, and found that reconstitutive expression of full length HA-XIAP and HA-XIAP ΔBIR, both of which have intact RING domain, restored β-Actin expression, actin polymerization and cancer cell motility. Whereas introduction of HA-XIAP ΔRING or H467A mutant, which abolished its E3 ligase function, did not show obvious restoration, demonstrating that E3 ligase activity of XIAP RING domain played a crucial role of XIAP in regulation of cancer cell motility. Moreover, RING domain rather than BIR domain was required for interaction with RhoGDI independent on its E3 ligase activity. To sum up, our present studies found that role of XIAP in regulating cellular motility was uncoupled from its caspase-inhibitory properties, but related to physical interaction between RhoGDI and its RING domain. Although E3 ligase activity of RING domain contributed to cell migration, it was not involved in RhoGDI binding nor its ubiquitinational modification

Pre-Stimulus Activity Predicts the Winner of Top-Down vs. Bottom-Up Attentional Selection

Our ability to process visual information is fundamentally limited. This leads to competition between sensory information that is relevant for top-down goals and sensory information that is perceptually salient, but task-irrelevant. The aim of the present study was to identify, from EEG recordings, pre-stimulus and pre-saccadic neural activity that could predict whether top-down or bottom-up processes would win the competition for attention on a trial-by-trial basis. We employed a visual search paradigm in which a lateralized low contrast target appeared alone, or with a low (i.e., non-salient) or high contrast (i.e., salient) distractor. Trials with a salient distractor were of primary interest due to the strong competition between top-down knowledge and bottom-up attentional capture. Our results demonstrated that 1) in the 1-sec pre-stimulus interval, frontal alpha (8–12 Hz) activity was higher on trials where the salient distractor captured attention and the first saccade (bottom-up win); and 2) there was a transient pre-saccadic increase in posterior-parietal alpha (7–8 Hz) activity on trials where the first saccade went to the target (top-down win). We propose that the high frontal alpha reflects a disengagement of attentional control whereas the transient posterior alpha time-locked to the saccade indicates sensory inhibition of the salient distractor and suppression of bottom-up oculomotor capture

Target Cueing Provides Support for Target- and Resource-Based Models of the Attentional Blink

The attentional blink (AB) describes a time-based deficit in processing the second of two masked targets. The AB is attenuated if successive targets appear between the first and final target, or if a cueing target is positioned before the final target. Using various speeds of stimulus presentation, the current study employed successive targets and cueing targets to confirm and extend an understanding of target-target cueing in the AB. In Experiment 1, three targets were presented sequentially at rates of 30 msec/item or 90 msec/item. Successive targets presented at 90 msec improved performance compared with non-successive targets. However, accuracy was equivalently high for successive and non-successive targets presented at 30 msec/item, suggesting that–regardless of whether they occurred consecutively–those items fell within the temporally defined attentional window initiated by the first target. Using four different presentation speeds, Experiment 2 confirmed the time-based definition of the AB and the success of target-cueing at 30 msec/item. This experiment additionally revealed that cueing was most effective when resources were not devoted to the cue, thereby implicating capacity limitations in the AB. Across both experiments, a novel order-error measure suggested that errors tend to decrease with an increasing duration between the targets, but also revealed that certain stimulus conditions result in stable order accuracy. Overall, the results are best encapsulated by target-based and resource-sharing theories of the AB, which collectively value the contributions of capacity limitations and optimizing transient attention in time

Prognostic indices for brain metastases – usefulness and challenges

<p>Abstract</p> <p>Background</p> <p>This review addresses the strengths and weaknesses of 6 different prognostic indices, published since the Radiation Therapy Oncology Group (RTOG) developed and validated the widely used 3-tiered prognostic index known as recursive partitioning analysis (RPA) classes, i.e. between 1997 and 2008. In addition, other analyses of prognostic factors in groups of patients, which typically are underrepresented in large trials or databases, published in the same time period are reviewed.</p> <p>Methods</p> <p>Based on a systematic literature search, studies with more than 20 patients were included. The methods and results of prognostic factor analyses were extracted and compared. The authors discuss why current data suggest a need for a more refined index than RPA.</p> <p>Results</p> <p>So far, none of the indices has been derived from analyses of all potential prognostic factors. The 3 most recently published indices, including the RTOG's graded prognostic assessment (GPA), all expanded from the primary 3-tiered RPA system to a 4-tiered system. The authors' own data confirm the results of the RTOG GPA analysis and support further evaluation of this tool.</p> <p>Conclusion</p> <p>This review provides a basis for further refinement of the current prognostic indices by identifying open questions regarding, e.g., performance of the ideal index, evaluation of new candidate parameters, and separate analyses for different cancer types. Unusual primary tumors and their potential differences in biology or unique treatment approaches are not well represented in large pooled analyses.</p

Prevalence and morphology of coronary artery ectasia with dual-source CT coronary angiography

To assess the prevalence and morphological characteristics of coronary artery ectasia (CAE) with CT coronary angiography (CTCA) in comparison to conventional catheterangiography (CCA). Dual-source CTCA examinations from 677 consecutive patients (223 women; median age 57 years) were retrospectively evaluated by two blinded observers for the presence of CAE defined as a diameter enlargement >/=1.5 times the diameter of adjacent normal coronary segments. Vessel diameters and contrast attenuation within and proximal to ectatic segments were measured. CCA was used to compare measurements obtained from CTCA with the coronary flow velocity by using the thrombolysis in myocardial infarction (TIMI) frame count. CTCA identified CAE in 20 of 677 (3%) patients. CCA was performed in ten of these patients. CAE diameter measurements with CTCA (10.0 +/- 5.4 mm) correlated significantly (r = 0.92, p < 0.001) with the CCA measurements (8.8 +/- 4.9 mm), but had higher diameters (levels of agreement: -1.0 to 3.4 mm). Contrast attenuation was significantly lower in the ectatic (343 +/- 63 HU) than in the proximal (394 +/- 60 HU) segments (p < 0.01). The attenuation difference significantly correlated with the CAE ratio (r = 0.67, p < 0.01) and the TIMI frame count (r = 0.58, p < 0.05). The prevalence of CAE in a population examined by CTCA is around 3%. Contrast attenuation measurements with CTCA correlate well with the flow alterations assessed with CCA

Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer

Background: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin–eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. Methods: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. Results: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. Conclusions: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations

Менеджмент інноваціями в контексті оцінювання екологічної, соціальної та управлінської ефективності, та сталого розвитку з урахуванням ESG-ефектів: дослідження країн, що розвиваються

Рейтинги компаній за рівнем екологічної, соціальної та управлінської ефективності (Environment, Social, and Governance, ESG) стали визначальними показниками для оцінки поведінки корпорацій у контексті досягнення цілей сталого розвитку. Метою даної статті є розгляд взаємозв'язків між ESG-ефектами та сталим розвитком підприємств, зокрема в контексті управлінського обліку та інновацій. Авторами проаналізовано ефективність управління інноваціями промисловими підприємствами Туреччини, враховуючи ESG-рейтинг на основі даних Refinitiv Eikon's listing. Для перевірки висунутих гіпотез використано метод часткових найменших квадратів (Partial Least Squares, PLS) із бутстрепінгом. Емпіричні розрахунки здійснено з використанням програмного забезпечення Smart-PLS 4.0. Результати дослідження підтвердили, що управління інноваціями в промисловому секторі Туреччини має статистично значущий вплив на сталий розвиток компаній та рівень екологічної, соціальної та управлінської ефективності. Це свідчить про важливість цього питання у контексті управлінського обліку. Дослідження підтверджує, що управління інноваціями є необхідною умовою для досягнення сталого розвитку промислових компаній. З огляду на це, менеджмент компаній повинен враховувати екологічні, соціальні та управлінські аспекти при формулюванні цілей, завдань, плануванні та розробці стратегій розвитку. Автори акцентують, що врахування основних принципів ESG-концепції у процесі прийняття рішень створює передумови для досягнення визначених цілей сталого розвитку. Результати дослідження можуть бути корисними для керівників промислових підприємств та уряду країни при формуванні стратегій, спрямованих на одночасне забезпечення економічного зростання та досягнення цілей сталого розвитку.Based on managerial accounting, Ratings for the environment, society, and governance (ESG) are now crucial measures for assessing how corporations behave with respect to sustainability. This study aims to present research in the managerial accounting and innovation field to determine how industrial firms' sustainability performance and associated ESG scores relate to one another. This study especially evaluates the management of innovations in the manufacturing industry in terms of Turkey's ESG performance ratings based on Refinitiv Eikon's listing. To examine the association between the management of innovations in industrial firms' overall sustainability performance and ESG scores, hypotheses were developed and tested. Cutting-edge Smart-PLS 4.0 software was used to carry out a rigorous partial least squares (PLS) analysis together with conventional bootstrapping to accomplish these goals. The results show that the management of innovations in Turkey's manufacturing sector's sustainability performance is strongly impacted by all ESG issues (social, governance, and environmental scores), which makes it a vital issue from the perspective of the managerial accounting field. The present research emphasizes the management of innovations as a crucial part of determining the sustainability of the industrial sector’s environment. The assignment of goals when conducting planning and policy making should appropriately take into account ESG-related factors, according to the key findings of this study. Industrial firms can improve their overall sustainability performance and make good contributions to the well-being of innovations, the environment and society while upholding sound governance standards by incorporating ESG concepts into decision-making processes. For the purpose of developing strategies that balance economic growth with sustainable development objectives, this research offers insightful information to industrial executives and legislators