Writing a wrong: Coupled RNA polymerase II transcription and RNA quality control

Processing and maturation of precursor RNA species is coupled to RNA polymerase II transcription. Co-transcriptional RNA processing helps to ensure efficient and proper capping, splicing, and 3' end processing of different RNA species to help ensure quality control of the transcriptome. Many improperly processed transcripts are not exported from the nucleus, are restricted to the site of transcription, and are in some cases degraded, which helps to limit any possibility of aberrant RNA causing harm to cellular health. These critical quality control pathways are regulated by the highly dynamic protein-protein interaction network at the site of transcription. Recent work has further revealed the extent to which the processes of transcription and RNA processing and quality control are integrated, and how critically their coupling relies upon the dynamic protein interactions that take place co-transcriptionally. This review focuses specifically on the intricate balance between 3' end processing and RNA decay during transcription termination. This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Processing > 3' End Processing RNA Processing > Splicing Mechanisms RNA Processing > Capping and 5' End Modifications

Can Customers Detect Script Usage in Service Encounters? An Experimental Video Analysis

Service scripts are predetermined guides for employees to follow when delivering service to customers. Some services require employees to strictly follow a script, whereas others use scripts more flexibly, if at all. Extant research regarding service scripts in the domain of service operations has mainly addressed the topic from more of a process view as a control mechanism for the encounter but minimal research has examined customer perceptions of scripted service. The authors examine a pivotal first question, which is if customers can detect different approaches to script use. To answer the question, the authors conducted a video experiment of face‐to‐face service encounters in the hospitality industry. The results indicate that customers can detect degrees of script use across both standardized and customized encounter types. This work serves as initial empirical evidence that customers are indeed capable of detecting subtleties in scripting approaches in different service situations and supports that script level is an important service design construct for research. Furthermore, the authors highlight the use of a video experiment as an innovative methodology for assessing customer perceptions of intangible aspects to services in a realistic setting. One implication of this study is that managers need to assess the impact that different script levels have on customer perceptions of various service performance measures. Managers should also consider the effect script detection has on customer perceptions of the service experience and service brand to assure their script approach aligns with the organization’s service strategy

ИСТОРИЯ КАРНАВАЛА

Сегодня во всех странах мира широко распространены карнавалы и фестивали (Бразилия, США, Колумбия, Боливия, Германия, Италия и т. д.). В настоящее время масштаб праздника в большей степени определяется желанием выражения местной культуры, и, конечно, его использованием в качестве простого развлечения для участников. Таким образом, можно сказать, что главная роль карнавала заключается в сохранении культуры и традиций, которые отражают национальную картину мира в единстве с общими и специфическими чертами отдельно взятого карнавала. Поэтому для современных людей и ученых разных направлений проблема исследования карнавала является актуальной. В статье анализируются различные гипотезы происхождения карнавала, история его развития в Европе, особенно в Италии и Бельгии, и его последующее распространение и история в Латинской Америке: в Бразилии и Боливии

Magnetic properties and magnetocaloric effects in GdCo9Si2 compound with multiple magnetic phase transitions

The structure and magnetic properties of polycrystalline GdCo9Si2 compound have been investigated. It has a BaCd11 structure and undergoes two magnetic phase transitions: an antiferromagnetic to ferrimagnetic transition occurring at rv93 K, and a ferrimagnetic to paramagnetic transition at 420 K, which results in a positive and a negative magnetic entropy change, respectively. The two peak values of magnetic entropy change are -0.6 and 1.1 J·kg-1 K-1 for DH ¼ 5 T. Furthermore, there exists a metal-semiconductor transition temperature (TP), below which the resistance increases with increasing temperature, while the semiconductor characteristic is observed above TP. The magnetic domain structures are characterized by stripe and grid structures 1 lm wide. Although the MCE is small for applications, its study is useful to clearly understand the nature of multiple magnetic phase transitions in the GdCo9Si2 compound

Optimizing the Curie temperature of pseudo-binary RxR'2-xFe17 (R,R' = rare earth) for magnetic refrigeration

Several pseudo-binary RxR'2-xFe17 alloys (with R = Y, Ce, Pr, Gd and Dy) were synthesized with rhombohedral Th2Zn17-type crystal structure determined from x-ray and neutron powder diffraction. The choice of compositions was done with the aim of tuning the Curie temperature (TC) in the 270 ± 20 K temperature range, in order to obtain the maximum magneto-caloric effect around room temperature. The investigated compounds exhibit broad isothermal magnetic entropy changes, ΔSM(T), with moderate values of the refrigerant capacity, even though the values of ΔSMPeak are relatively low compared with those of the R2Fe17 compounds with R = Pr or Nd. The reduction on the ΔSMPeak is explained in terms of the diminution in the saturation magnetization value. Furthermore, the ΔSM(T) curves exhibit a similar caret-like behavior, suggesting that the magneto-caloric effect is mainly governed by the Fe-sublattice. A single master curve for ΔSM/ΔSMPeak(T) under different values of the magnetic field change are obtained for each compound by rescaling of the temperature axis.España MICINN MAT2011-27573-C04Basque Government IT-347-07CONACYT CB-2010-01-156932Slovak R&D Agency VVCE-0058-0

Magneto-caloric effect in the pseudo-binary intermetallic YPrFe17 compound

We have synthesized the intermetallic YPrFe17 compound by arc-melting. X-ray and neutron powder diffraction show that the crystal structure is rhombohedral with View the MathML source space group (Th2Zn17-type). The investigated compound exhibits a broad isothermal magnetic entropy change {\Delta}SM(T) associated with the ferro-to-paramagnetic phase transition (TC \approx 290 K). The |{\Delta}SM| (\approx 2.3 J kg-1 K-1) and the relative cooling power (\approx 100 J kg-1) have been calculated for applied magnetic field changes up to 1.5 T. A single master curve for {\Delta}SM under different values of the magnetic field change can be obtained by a rescaling of the temperature axis. The results are compared and discussed in terms of the magneto-caloric effect in the isostructural R2Fe17 (R = Y, Pr and Nd) binary intermetallic alloys.Comment: Preprint, 5 pages (postprint), 4 figures, regular pape

O Conflito Político. Alguns Aspectos da sua Modelação

Objective: Sports practice alters the homeostasis of athletes. To achieve homeostatic equilibrium, the integrated action of the neuroendocrine and immune systems is necessary. Here we studied the relation between cytokines, hormones and mood states in marathon runners. Methods: A total of 20 male recreational marathon runners (mean age = 35.7 ± 9 years) and 20 male sedentary individuals (mean age = 35.5 ± 7 years) were recruited. We compared the serum levels of growth hormone (GH), cortisol and interleukins 8 and 10 and the amounts of these two cytokines spontaneously produced by peripheral blood mononuclear cells. Blood samples of the sedentary group were collected at rest. Blood from the marathon runners was collected at rest (baseline: 24 h before the race), immediately after a marathon and 72 h after a marathon. Mood state analysis in both groups was performed using the 24-item Brunel Mood Scale (BRUMS). Results: Our results showed that, at rest, levels of interleukins 8 and 10 in the supernatant of culture cells, the serum concentration of GH, and tension and vigour (evaluated using the BRUMS), were significantly higher in athletes compared to sedentary people. Immediately after the race all serum parameters analysed were statistically higher than baseline values. At 72 h after the marathon, serum levels of hormones and interleukins returned to values at rest, but the concentrations of interleukins in the supernatant of culture cells showed a significant reduction compared to values at rest. Conclusion: The higher serum levels of GH in athletes at rest and the higher production of cytokines in culture without previous stimulus suggest that marathon runners present mechanisms that may be associated with preparing the body to perform prolonged strenuous exercise, such as a marathon

Major CD4 T-Cell Depletion and Immune Senescence in a Patient with Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) results from primary defects in phagocytic reactive oxygen species (ROS) production. T-cell evaluation is usually neglected during patients’ follow-up, although T-cell depletion has been reported in CGD through unknown mechanisms. We describe here a 36-year-old patient with X-linked CGD with severe CD4 T-cell depletion <200 CD4 T-cells/μl, providing insights into the mechanisms that underlie T-cell loss in the context of oxidative burst defects. In addition to the typical infections, the patient featured a progressive T-cell loss associated with persistent lymphocyte activation, expansion of interleukin (IL)-17-producing CD4 T-cells, and impaired thymic activity, leading to a reduced replenishment of the T-cell pool. A relative CD4 depletion was also found at the gut mucosal level, although no bias to IL-17-production was documented. This immunological pattern of exhaustion of immune resources favors prompt, potentially curative, therapeutic interventions in CGD patients, namely, stem-cell transplantation or gene therapy. Moreover, this clinical case raises new research questions on the interplay of ROS production and T-cell homeostasis and immune senescence

Selective inhibition of pancreatic ductal adenocarcinoma cell growth by the mitotic MPS1 kinase inhibitor NMS-P715

Most solid tumors, including pancreatic ductal adenocarcinoma (PDAC), exhibit structural and numerical chromosome instability (CIN). Although often implicated as a driver of tumor progression and drug resistance, CIN also reduces cell fitness and poses a vulnerability that can be exploited therapeutically. The spindle assembly checkpoint (SAC) ensures correct chromosome-microtubule attachment, thereby minimizing chromosome segregation errors. Many tumors exhibit upregulation of SAC components such as MPS1, which may help contain CIN within survivable limits. Prior studies showed that MPS1 inhibition with the small molecule NMS-P715 limits tumor growth in xenograft models. In cancer cell lines, NMS-P715 causes cell death associated with impaired SAC function and increased chromosome missegregation. Although normal cells appeared more resistant, effects on stem cells, which are the dose-limiting toxicity of most chemotherapeutics, were not examined. Elevated expression of 70 genes (CIN70), including MPS1, provides a surrogate measure of CIN and predicts poor patient survival in multiple tumor types. Our new findings show that the degree of CIN70 upregulation varies considerably among PDAC tumors, with higher CIN70 gene expression predictive of poor outcome. We identified a 25 gene subset (PDAC CIN25) whose overexpression was most strongly correlated with poor survival and included MPS1. In vitro, growth of human and murine PDAC cells is inhibited by NMS-P715 treatment, whereas adipose-derived human mesenchymal stem cells are relatively resistant and maintain chromosome stability upon exposure to NMS-P715. These studies suggest that NMS-P715 could have a favorable therapeutic index and warrant further investigation of MPS1 inhibition as a new PDAC treatment strategy