The U7 snRNP and the hairpin binding protein: Key players in histone mRNA metabolism.

Animal replication-dependent histone mRNAs are subject to several post-transcriptional regulatory processes. Their non-polyadenylated 3' ends are formed preferentially during S phase by a unique nuclear cleavage event. This requires the base pairing between U7 snRNA and a histone spacer element 3' of the cleavage site. Cleavage occurs preferentially after adenosine, at a fixed distance from the hybrid region. A conserved RNA hairpin just upstream of the cleavage site is recognised by the hairpin binding protein (HBP) that acts as an auxiliary processing factor, stabilising the interaction of the histone pre-mRNA with the U7 snRNP. The interaction between HBP and the RNA hairpin is very stable and HBP is also found associated with histone mRNAs on polysomes. The hairpin and presumably, HBP are also required for nuclear export and translation of histone mRNA. Furthermore, histone mRNAs are selectively destabilised in the G2 phase or upon inhibition of DNA synthesis and this regulation is also associated with the hairpin. Recently, HBP-encoding cDNAs were isolated from various organisms. Human, mouse and Xenopus laevis HBPs are similar, while the Caenorhabditis elegans protein has significant homology to the others only in a central RNA binding domain.Copyright 1997 Academic Press Limited

Left atrial remodeling, early repolarization pattern, and inflammatory cytokines in professional soccer players

OBJECTIVES: Although regular physical exercise clearly reduces cardiovascular morbidity risk, long-term endurance sports practice has been recognized as a risk factor for atrial fibrillation (AF). However, the mechanisms how endurance sports can lead to AF are not yet clear. The aim of our present study was to investigate the influence of long-term endurance training on vagal tone, atrial size, and inflammatory profile in professional elite soccer players. METHODS: A total of 25 professional major league soccer players (mean age 24+/-4 years) and 20 sedentary controls (mean age 26+/-3 years) were included in the study and consecutively examined. All subjects underwent a sports cardiology check-up with physical examination, electrocardiography, echocardiography, exercise testing on a bicycle ergometer, and laboratory analysis [standard laboratory and cytokine profile: interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, IL-8, IL-10]. RESULTS: Athletes were divided into two groups according to presence or absence of an early repolarization (ER) pattern, defined as a ST-segment elevation at the J-point (STE) >/=0.1mm in 2 leads. Athletes with an ER pattern showed significantly lower heart rate and an increased E/e' ratio compared to athletes without an ER pattern. STE significantly correlated with E/e' ratio as well as with left atrial (LA) volume. The pro-inflammatory cytokines IL-6, IL-8, TNF-alpha as well as the anti-inflammatory cytokine IL-10 were significantly elevated in all soccer players. However, athletes with an ER pattern had significantly higher IL-6 plasma levels than athletes without ER pattern. Furthermore, athletes with "high" level IL-6 had significantly larger LA volumes than players with "low" level IL-6. CONCLUSIONS: Athletes with an ER pattern had significantly higher E/e' ratios, reflecting higher atrial filling pressures, higher LA volume, and higher IL-6 plasma levels. All these factors may contribute to atrial remodeling over time and thus increase the risk of AF in long-term endurance sports.

OsteoMacs: Key players around bone biomaterials.

Osteal macrophages (OsteoMacs) are a special subtype of macrophage residing in bony tissues. Interesting findings from basic research have pointed to their vast and substantial roles in bone biology by demonstrating their key function in bone formation and remodeling. Despite these essential findings, much less information is available concerning their response to a variety of biomaterials used for bone regeneration with the majority of investigation primarily focused on their role during the foreign body reaction. With respect to biomaterials, it is well known that cells derived from the monocyte/macrophage lineage are one of the first cell types in contact with implanted biomaterials. Here they demonstrate extremely plastic phenotypes with the ability to differentiate towards classical M1 or M2 macrophages, or subsequently fuse into osteoclasts or multinucleated giant cells (MNGCs). These MNGCs have previously been characterized as foreign body giant cells and associated with biomaterial rejection, however more recently their phenotypes have been implicated with wound healing and tissue regeneration by studies demonstrating their expression of key M2 markers around biomaterials. With such contrasting hypotheses, it becomes essential to better understand their roles to improve the development of osteo-compatible and osteo-promotive biomaterials. This review article expresses the necessity to further study OsteoMacs and MNGCs to understand their function in bone biomaterial tissue integration including dental/orthopedic implants and bone grafting materials.

Impairments of peripheral motion change detection during smooth pursuit eye movements

Introduction: In team sports the ability to use peripheral vision is essential to track a number of players and the ball. By using eye-tracking devices it was found that players either use fixations and saccades to process information on the pitch or use smooth pursuit eye movements (SPEM) to keep track of single objects (Schütz, Braun, & Gegenfurtner, 2011). However, it is assumed that peripheral vision can be used best when the gaze is stable while it is unknown whether motion changes can be equally well detected when SPEM are used especially because contrast sensitivity is reduced during SPEM (Schütz, Delipetkose, Braun, Kerzel, & Gegenfurtner, 2007). Therefore, peripheral motion change detection will be examined by contrasting a fixation condition with a SPEM condition. Methods: 13 participants (7 male, 6 female) were presented with a visual display consisting of 15 white and 1 red square. Participants were instructed to follow the red square with their eyes and press a button as soon as a white square begins to move. White square movements occurred either when the red square was still (fixation condition) or moving in a circular manner with 6 °/s (pursuit condition). The to-be-detected white square movements varied in eccentricity (4 °, 8 °, 16 °) and speed (1 °/s, 2 °/s, 4 °/s) while movement time of white squares was constant at 500 ms. 180 events should be detected in total. A Vicon-integrated eye-tracking system and a button press (1000 Hz) was used to control for eye-movements and measure detection rates and response times. Response times (ms) and missed detections (%) were measured as dependent variables and analysed with a 2 (manipulation) x 3 (eccentricity) x 3 (speed) ANOVA with repeated measures on all factors. Results: Significant response time effects were found for manipulation, F(1,12) = 224.31, p < .01, ηp2 = .95, eccentricity, F(2,24) = 56.43; p < .01, ηp2 = .83, and the interaction between the two factors, F(2,24) = 64.43; p < .01, ηp2 = .84. Response times increased as a function of eccentricity for SPEM only and were overall higher than in the fixation condition. Results further showed missed events effects for manipulation, F(1,12) = 37.14; p < .01, ηp2 = .76, eccentricity, F(2,24) = 44.90; p < .01, ηp2 = .79, the interaction between the two factors, F(2,24) = 39.52; p < .01, ηp2 = .77 and the three-way interaction manipulation x eccentricity x speed, F(2,24) = 3.01; p = .03, ηp2 = .20. While less than 2% of events were missed on average in the fixation condition as well as at 4° and 8° eccentricity in the SPEM condition, missed events increased for SPEM at 16 ° eccentricity with significantly more missed events in the 4 °/s speed condition (1 °/s: M = 34.69, SD = 20.52; 2 °/s: M = 33.34, SD = 19.40; 4 °/s: M = 39.67, SD = 19.40). Discussion: It could be shown that using SPEM impairs the ability to detect peripheral motion changes at the far periphery and that fixations not only help to detect these motion changes but also to respond faster. Due to high temporal constraints especially in team sports like soccer or basketball, fast reaction are necessary for successful anticipation and decision making. Thus, it is advised to anchor gaze at a specific location if peripheral changes (e.g. movements of other players) that require a motor response have to be detected. In contrast, SPEM should only be used if a single object, like the ball in cricket or baseball, is necessary for a successful motor response. References: Schütz, A. C., Braun, D. I., & Gegenfurtner, K. R. (2011). Eye movements and perception: A selective review. Journal of Vision, 11, 1-30. Schütz, A. C., Delipetkose, E., Braun, D. I., Kerzel, D., & Gegenfurtner, K. R. (2007). Temporal contrast sensitivity during smooth pursuit eye movements. Journal of Vision, 7, 1-15.