STAT3 noncell-autonomously controls planar cell polarity during zebrafish convergence and extension

Zebrafish signal transducer and activator of transcription 3 (STAT3) controls the cell movements during gastrulation. Here, we show that noncell-autonomous activity of STAT3 signaling in gastrula organizer cells controls the polarity of neighboring cells through Dishevelled-RhoA signaling in the Wnt-planar cell polarity (Wnt-PCP) pathway. In STAT3-depleted embryos, although all the known molecules in the Wnt-PCP pathway were expressed normally, the RhoA activity in lateral mesendodermal cells was down-regulated, resulting in severe cell polarization defects in convergence and extension movements identical to Strabismus-depleted embryos. Cell-autonomous activation of Wnt-PCP signaling by ΔN-dishevelled rescued the defect in cell elongation, but not the orientation of lateral mesendodermal cells in STAT3-depleted embryos. The defect in the orientation could be rescued by transplantation of shield cells having noncell-autonomous activity of STAT3 signaling. These results suggest that the cells undergoing convergence and extension movement may sense the gradient of signaling molecules, which are expressed in gastrula organizer by STAT3 and noncell-autonomously activate PCP signaling in neighboring cells during zebrafish gastrulation

Autonomic nervous alterations associated with daily level of fatigue

<p>Abstract</p> <p>Background</p> <p>Fatigue is a common symptom in both sick and healthy people. We examined autonomic nervous alterations associated with fatigue to clarify the mechanisms underlying fatigue.</p> <p>Methods</p> <p>The study group consisted of 19 healthy participants who performed a 2-back test for 30 min as a fatigue-inducing mental task session. Before and after the session, they completed the advanced trail making test (ATMT) for 30 min for mental fatigue evaluation, subjective scales to measure fatigue sensation, and underwent electrocardiography to allow assessment of autonomic nerve activities.</p> <p>Results</p> <p>After the fatigue-inducing task, the total error counts on the ATMT tended to increase (<it>P </it>= 0.076); the ATMT for total trial counts (<it>P </it>= 0.001), the subjective level of fatigue (<it>P </it>< 0.001), and the % low-frequency power (%LF) (<it>P </it>= 0.035) increased significantly; and the % high-frequency power (%HF) decreased compared with before the fatigue-inducing task although this did not reach the statistical significance (<it>P </it>= 0.170). Although LF measured in absolute units did not change significantly before and after the fatigue-inducing task (<it>P </it>= 0.771), and HF measured in absolute units decreased after the task (<it>P </it>= 0.020). The %LF and LF/HF ratio were positively associated with the daily level of fatigue evaluated using Chalder's fatigue scale. In addition, %HF was negatively associated with the fatigue score.</p> <p>Conclusions</p> <p>Increased sympathetic activity and decreased parasympathetic activity may be characteristic features of both acute and daily levels of fatigue. Our findings provide new perspectives on the mechanisms underlying fatigue.</p

UV-Induced Ubiquitylation of XPC Protein Mediated by UV-DDB-Ubiquitin Ligase Complex

SummaryThe xeroderma pigmentosum group C (XPC) protein complex plays a key role in recognizing DNA damage throughout the genome for mammalian nucleotide excision repair (NER). Ultraviolet light (UV)-damaged DNA binding protein (UV-DDB) is another complex that appears to be involved in the recognition of NER-inducing damage, although the precise role it plays and its relationship to XPC remain to be elucidated. Here we show that XPC undergoes reversible ubiquitylation upon UV irradiation of cells and that this depends on the presence of functional UV-DDB activity. XPC and UV-DDB were demonstrated to interact physically, and both are polyubiquitylated by the recombinant UV-DDB-ubiquitin ligase complex. The polyubiquitylation altered the DNA binding properties of XPC and UV-DDB and appeared to be required for cell-free NER of UV-induced (6-4) photoproducts specifically when UV-DDB was bound to the lesion. Our results strongly suggest that ubiquitylation plays a critical role in the transfer of the UV-induced lesion from UV-DDB to XPC