Sleep loss impairs waking functions and is homeostatically compensated in recovery sleep. The mechanisms underlying the consequences of prolonged wakefulness are unknown. The stimulant modafinil may promote primarily dopaminergic neurotransmission. Catechol‐O‐methyltransferase (COMT) catalyzes the breakdown of cerebral dopamine. A functional Val158Met polymorphism reduces COMT activity, and Val/Val homozygous individuals presumably have lower dopaminergic signaling in the prefrontal cortex than do Met/Met homozygotes. We quantified the contribution of this polymorphism to the effects of sleep deprivation and modafinil on subjective state, cognitive performance, and recovery sleep in healthy volunteers. Two‐time 100 mg modafinil potently improved vigor and well‐being, and maintained baseline performance with respect to executive functioning and vigilant attention throughout sleep deprivation in Val/Val genotype subjects but was hardly effective in subjects with the Met/Met genotype. Neither modafinil nor the Val158Met polymorphism affected distinct markers of sleep homeostasis in recovery sleep. In conclusion, dopaminergic mechanisms contribute to impaired waking functions after sleep loss. Clinical Pharmacology & Therapeutics (2009); 85, 3, 296–304 doi:

Transposable elements (TEs) make up a majority of a typical eukaryote’s genome, and contribute to cell heterogeneity in unclear ways. Single-cell sequencing technologies are powerful tools to explore cells, however analysis is typically gene-centric and TE expression has not been addressed. Here, we develop a single-cell TE processing pipeline, scTE, and report the expression of TEs in single cells in a range of biological contexts. Specific TE types are expressed in subpopulations of embryonic stem cells and are dynamically regulated during pluripotency reprogramming, differentiation, and embryogenesis. Unexpectedly, TEs are expressed in somatic cells, including human disease-specific TEs that are undetectable in bulk analyses. Finally, we apply scTE to single-cell ATAC-seq data, and demonstrate that scTE can discriminate cell type using chromatin accessibly of TEs alone. Overall, our results classify the dynamic patterns of TEs in single cells and their contributions to cell heterogeneity.

Highlights d Setdb1-KO fails to induce trophectoderm (TE) differentiation in ''ground-state'' ESCs d Setdb1 deficiency initiates 2C-like transition program in a Dux-dependent manner d Nanog overexpression suppresses 2C-like transition induced by Setdb1-KO d The ''ground-state'' Setdb1-null ESCs undergo necroptosis by activating Ripk3

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N 6 -methyladenosine (m 6 A), the most abundant reversible modification on eukaryote messenger RNA, is recognized by a series of readers, including the YT521-B homology domain family (YTHDF) proteins, which are coupled to perform physiological functions. Here, we report that YTHDF2 and YTHDF3, but not YTHDF1, are required for reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). Mechanistically, we found that YTHDF3 recruits the PAN2-PAN3 deadenylase complex and conduces to reprogramming by promoting mRNA clearance of somatic genes, including Tead2 and Tgfb1, which parallels the activity of the YTHDF2-CCR4-NOT deadenylase complex. Ythdf2/3 deficiency represses mesenchymal-to-epithelial transition (MET) and chromatin silencing at loci containing the TEAD motif, contributing to decreased reprogramming efficiency. Moreover, RNA interference of Tgfb1 or the Hippo signaling effectors Yap1, Taz, and Tead2 rescues Ythdf2/3-defective reprogramming. Overall, YTHDF2/3 couples RNA deadenylation and regulation with the clearance of somatic genes and provides insights into iPSC reprogramming at the posttranscriptional level.

A novel ultraviolet (UV) absorber, 5,5′‐disulfide‐bis[2‐(2‐hydroxy‐3,5‐di‐tert‐butylphenyl)‐2Hbenzotriazole] (DSBHTBB) was synthesized. Its structure was characterized by FTIR, NMR, UV, FABMS, and elemental analysis. In comparison with the common commercial benzotriazole UV absorbers, the absorption maximum of DSBHTBB (364 nm) is red shifted by about 20 nm, and the molar extinction coefficient (56,800, in CHCl3) is much greater. With those properties the bisbenzotriazole could be applied as an efficient UV absorber for the protection of polymeric materials and sensitive skin from longer‐wavelength (near‐visible) ultraviolet light. The experimental results showed that DSBHTBB can greatly inhibit the discoloration under irradiation of poly (vinyl chloride) (PVC) containing an organic antimony stabilizer. J. VINYL ADDIT. TECHNOL., 13:195–200, 2007. © 2007 Society of Plastics Engineers

The China Spallation Neutron Source (CSNS) uses H − stripping and phase space painting method to fill large ring acceptance with the linac beam of small emittance. The dependence of the painting beam on the injection beam parameters was studied for the Rapid Cycling Synchrotron (RCS) of CSNS. The injection processes for different momentum spread, rms emittance of the injection beam, injection beam matching were simulated, then the beam losses, 99% and rms emittances were obtained and the optimized ranges of injection beam parameters were given. The interaction between the H − beam and the stripping foil was studied and the foil scattering was simulated. Then, the stripping efficiency was calculated and the suitable thickness of the stripping foil was obtained. The energy deposition on the foil and the beam losses due to the foil scattering were also studied.

The transition from pluripotent to somatic states marks a critical event in mammalian development, but remains largely unresolved. Here we report the identification of SS18 as a regulator for pluripotent to somatic transition or PST by CRISPR-based whole genome screens. Mechanistically, SS18 forms microscopic condensates in nuclei through a C-terminal intrinsically disordered region (IDR) rich in tyrosine, which, once mutated, no longer form condensates nor rescue SS18−/− defect in PST. Yet, the IDR alone is not sufficient to rescue the defect even though it can form condensates indistinguishable from the wild type protein. We further show that its N-terminal 70aa is required for PST by interacting with the Brg/Brahma-associated factor (BAF) complex, and remains functional even swapped onto unrelated IDRs or even an artificial 24 tyrosine polypeptide. Finally, we show that SS18 mediates BAF assembly through phase separation to regulate PST. These studies suggest that SS18 plays a role in the pluripotent to somatic interface and undergoes liquid-liquid phase separation through a unique tyrosine-based mechanism.