Histone chaperones assemble and disassemble nucleosomes in an ATP-independent manner and thus regulate the most fundamental step in the alteration of chromatin structure. The molecular mechanisms underlying histone chaperone activity remain unclear. To gain insights into these mechanisms, we solved the crystal struc

In vertebrates, a rise in intracellular free Ca2+ (Ca2+i) levels during fertilization initiates second metaphase (mII) exit and the developmental programme. The Ca2+ rise has long been considered to be crucial for development, but verifying this contribution would benefit from defining its role during fertilization. Here, we delineate the role of Ca2+ release during mII exit in wild-type mouse eggs and show that it is dispensable for full-term development. Exit from mII can be induced by Zn2+-specific sequestration without Ca2+ release, eliciting Cyclin B degradation in a manner dependent upon the proteasome pathway and intact microtubules, but not accompanied by degradation of the meiotic regulator Emi2. Parthenogenotes generated by Zn2+ sequestration developed in vitro with normal expression of Ca2+-sensitive genes. Meiotic exit induced by either Ca2+ oscillations or a single Ca2+ rise in oocytes containing a signaling-deficient sperm resulted in comparable developmental rates. In the absence of Ca2+ release, full-term development occurred ∼50% less efficiently, but at readily detectable rates, with the birth of 27 offspring. These results show in intact mouse oocytes that Zn2+ is essential for mII arrest and suggest that triggering meiotic exit is the sole indispensable developmental role of Ca2+ signaling in mammalian fertilization.

Abstract. Zygotic gene activation (ZGA) is the first event of gene expression after fertilization. Following fertilization, ZGA occurs within a short time interval depending on the animal species. Until ZGA, maternal proteins and transcripts stored in oocytes control embryonic development, indicating the importance of maternal factors for development. Somatic cell cloning also proves the potential of oocyte to reprogram the differentiated cell nuclei to embryonic nuclei. Recent studies show that the epigenetic modifications of nuclei play important roles in controlling gene expression during ZGA. However, the mechanisms that control ZGA remain largely unknown. This review will cover the current understanding of ZGA. Specifically, it will focus on the maternal factors that control gene expression during early embryogenesis.

SUMMARYThe oocytes of vertebrates are typically arrested at metaphase II (mII) by the cytostatic factor Emi2 until fertilization. Regulatory mechanisms in Xenopus Emi2 (xEmi2) are understood in detail but contrastingly little is known about the corresponding mechanisms in mammals. Here, we analyze Emi2 and its regulatory neighbours at the molecular level in intact mouse oocytes. Emi2, but not xEmi2, exhibited nuclear targeting. Unlike xEmi2, separable N-and C-terminal domains of mouse Emi2 modulated metaphase establishment and maintenance, respectively, through indirect and direct mechanisms. The C-terminal activity was mapped to the potential phosphorylation target Tx 5 SxS, a destruction box (D-box), a lattice of Zn 2+ -coordinating residues and an RL domain. The minimal region of Emi2 required for its cytostatic activity was mapped to a region containing these motifs, from residue 491 to the C terminus. The cytostatic factor Mos-MAPK promoted Emi2-dependent metaphase establishment, but Mos autonomously disappeared from meiotically competent mII oocytes. The N-terminal Plx1-interacting phosphodegron of xEmi2 was apparently shifted to within a minimal fragment (residues 51-300) of mouse Emi2 that also contained a calmodulin kinase II (CaMKII) phosphorylation motif and which was efficiently degraded during mII exit. Two equimolar CaMKII  isoform variants were present in mII oocytes, neither of which phosphorylated Emi2 in vitro, consistent with the involvement of additional factors. No evidence was found that calcineurin is required for mouse mII exit. These data support a model in which mammalian meiotic establishment, maintenance and exit converge upon a modular Emi2 hub via evolutionarily conserved and divergent mechanisms.

The incidence rate, location, and timing of falls and performance of activities of daily living (ADLs) in 256 patients with stroke admitted to an 88-bed rehabilitation ward was observed with information on falls and level of ADLs upon admission extracted from patients' records. Of 273 falls among 121 of the 256 patients, 229 occurred in the patient's room or lavatory and 147 within 4 weeks of admission. Significant differences were detected between motor subscores under 64 and over 65 on the Functional Independence Measure (FIM) in fall proportional analysis. The mean fall rate in motor subclass of 26 to 38 was higher than in other subgroups. Those with cognitive subscore on the FIM lower than 29 were prone to fall. Also, deteriorated motor and cognitive functions were associated with a high risk of falls.