The PHD Finger/Bromodomain of NoRC Interacts with Acetylated Histone H4K16 and Is Sufficient for rDNA Silencing

SummaryThe SNF2h-containing chromatin-remodeling complex NoRC is responsible for silencing a fraction of mammalian rRNA genes (rDNA). NoRC silences transcription by establishing heterochromatic features—including DNA methylation, hypoacetylation of histone H4, and methylation of H3K9—at the rDNA promoter [1, 2]. We have investigated the mechanism of NoRC-mediated rDNA silencing and show that binding of the bromodomain of TIP5, the large subunit of NoRC, to acetylated nucleosomes is a prerequisite for NoRC function. A point mutation within the bromodomain impairs the association of NoRC with chromatin, prevents heterochromatin formation, and abolishes transcriptional repression. Moreover, the association of NoRC with chromatin requires acetylation of histone H4 at lysine 16 (acH4K16), and binding to acH4K16 is required for subsequent deacetylation of H4K5, H4K8, and H4K12, indicating that acetylation of H4K16 plays an active role in NoRC-mediated heterochromatin formation. The bromodomain cooperates with an adjacent PHD finger to recruit HDAC1, DNMT1, DNMT3, and SNF2h to rDNA. If specifically targeted to the rDNA promoter, the PHD finger/bromodomain is capable of establishing heterochromatic features and rDNA silencing. Thus, the PHD finger/bromodomain represents an autonomous unit that binds to acH4K16 and coordinates the chain of events that establish the repressed state of rDNA

Modular stem in total hip arthroplasty for patients with trochanter valgus deformity: surgical technique and case series.

BACKGROUND: Trochanter valgus deformity (TVD) is a rare condition of total hip arthroplasty (THA). Femoral osteotomy could be required in correcting the deformity to implant femoral stem in severe TVD. In this study, we described one unpublished technique of reverse sleeve of S-ROM to get through the complex situation. This study aimed to summarize and evaluate its technical challenges, safety and effectiveness. METHODS: From January 2006 to December 2014, we enrolled patients whose sleeves were implanted towards the great trochanter in THA with TVD. Their demographics, perioperative and postoperative information were recorded. To explore its indication, we measured and analyzed the ratio of greater trochanter/lesser trochanter (G/L ratio) and trochanter valgus angle (TVA). RESULTS: Twelve patients (1 male and 11 female, average age 42.30 ± 10.23) had mean follow-up of 6 years. Among them, only two patients had intraoperative femoral fracture. The survivorship of femoral prosthesis was 100%. The Harris hip score (HHS) increased from preoperative 34.31 ± 14.43 to postoperative 84.12 ± 11.33. All patients\u27 G/L ratio were larger than 1.50. CONCLUSIONS: The reverse sleeve of S-ROM was a reliable method for the patients with severe TVD, which brought satisfying clinical outcomes in mid-term follow-up

Prmt5 is a regulator of muscle stem cell expansion in adult mice.

Skeletal muscle stem cells (MuSC), also called satellite cells, are indispensable for maintenance and regeneration of adult skeletal muscles. Yet, a comprehensive picture of the regulatory events controlling the fate of MuSC is missing. Here, we determine the proteome of MuSC to design a loss-of-function screen, and identify 120 genes important for MuSC function including the arginine methyltransferase Prmt5. MuSC-specific inactivation of Prmt5 in adult mice prevents expansion of MuSC, abolishes long-term MuSC maintenance and abrogates skeletal muscle regeneration. Interestingly, Prmt5 is dispensable for proliferation and differentiation of Pax7(+) myogenic progenitor cells during mouse embryonic development, indicating significant differences between embryonic and adult myogenesis. Mechanistic studies reveal that Prmt5 controls proliferation of adult MuSC by direct epigenetic silencing of the cell cycle inhibitor p21. We reason that Prmt5 generates a poised state that keeps MuSC in a standby mode, thus allowing rapid MuSC amplification under disease conditions

How driving duration influences drivers' visual behaviors and fatigue awareness: a naturalistic truck driving test study

AbstractBackground: Commercial truck drivers stay behind the wheel for long hours. Fatigue is thus a major safety concern among such long distance travelling drivers.Objectives: Primarily, the study explored the effects of driving duration on commercial truck drivers’ visual features and fatigue awareness. It also examined the association between visual variables and subjective level of fatigue.Methods: Participants of the study were 36 commercial truck drivers. During the study, the participants were grouped into nine on the basis of the differences in their age and were made to participate in the naturalistic driving test. In the driving test, the participants were asked to finish 2h, 3h, and 4h continuous driving tasks. Ten visual indicators and self awareness of fatigue level of the drivers were recorded during the driving hours. One-way ANOVA and Pearson product-moment correlation were used to analyze each visual indicator’s variation by age groups over time, and its association with subjective level of fatigue.Results: The statistical analysis revealed that continuous driving duration had a significant effect on changes of visual indicators and self-reported fatigue level. After 2h of driving, both the average closure duration value and average subjective fatigue level changed significantly. After 4h of driving, other than the average number of saccades and average pupil diameter, all of the driver’s visual indicators had a significant change. In addition, the change of fatigue level is positively associated with the variation of pupil diameter, fixation duration, blink frequency, blink duration, and closure duration. On the other hand, the change of fatigue level was negatively related to number of fixations, search angle, number of saccade, saccade speed, and saccade amplitude.Conclusion: Driving duration has a significant effect on driver’s visual variation and fatigue level. For commercial truck drivers, traffic laws and regulations should strictly control the amount of their continuous driving time. Moreover, driving fatigue can also be evaluated through the change rate of driver’s visual indicators. Awareness of the rate of change in their driving fatigue level alerts drivers to the risk of fatigue and rest moment. [Ethiop. J. Health Dev. 2018;32(1):36-45

An Efficiency-Improved Tightly Coupled Dipole Reflectarray Antenna Using Variant-Coupling-Capacitance Method

In this paper, a tightly coupled dipole reflectarray antenna as well as a variant-coupling-capacitance method to improve the antenna aperture efficiency is presented. Tightly coupled elements and true-time-delay lines are employed in the design of a wideband reflectarray. The proposed reflectarray can operate from 2 GHz to 5 GHz with the gain varying from 11.3 dBi to 21 dBi. Moreover, we propose a variant-coupling-capacitance method to improve the reflectarray aperture efficiency at lower frequency. By changing the coupling capacitance between neighboring elements according to their positions in the reflecting surface, a more linear equivalent distance delay line is achieved. Hence, phase error is reduced. According to measurement, the reflectarray gain in 2 GHz using the proposed method is increased by 3 dBi compared with the previous design. Aperture efficiency in 2 GHz is improved by 21.6%