The Nature and Clinical Significance of Atypical Mononuclear Cells in Infectious Mononucleosis Caused by the Epstein-Barr Virus in Children.

Atypical mononuclear cells (AM) appear in significant numbers in peripheral blood of patients with Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). We investigated the number and lineage-specific clusters of differentiation (CD) expression of atypical mononuclear cells in 110 children with IM using the anti-CD antibody microarray for panning leukocytes by their surface markers prior to morphology examination. The AM population consisted primarily of CD8+ T cells with a small fraction (0%-2% of all lymphocytes) of CD19+ B lymphocytes. AM amount in children with mononucleosis caused by primary EBV infection was significantly higher than for IM caused by EBV reactivation or other viruses and constituted 1%-53% of all peripheral blood mononuclear cells compared to 0%-11% and 0%-8%, respectively. Children failing to recover from classic IM associated with primary EBV infection within 6 months had significantly lower percentage of CD8+ AM compared to patients with normal recovery rate.

Rat eggs cannot wait: Spontaneous exit from meiotic metaphase-II arrest.

Mammalian eggs await fertilisation while arrested at the second metaphase stage of meiotic division. A network of signalling pathways enables the establishment and maintenance of this metaphase-II arrest. In the absence of fertilisation, mammalian eggs can spontaneously exit metaphase II when parthenogenetically stimulated, or sometimes without any obvious stimulation. Ovulated rat eggs abortively release from metaphase-II arrest once removed from egg donors. Spontaneously activated rat eggs extrude the second polar body and proceed to the so-called metaphase III-'like' stage, with clumps of condensed chromatin scattered in the egg cytoplasm. It is still unclear what makes rat eggs susceptible to spontaneous activation; however, a vague picture of the signalling pathways involved in the process of spontaneous activation is beginning to emerge. Such cell cycle instability is one of the major reasons why it is more difficult to establish nuclear transfer in the rat. This review examines the known predisposing factors and biochemical mechanisms involved in spontaneous activation. The strategies used to prevent spontaneous metaphase-II release in rat eggs will also be discussed.

Lineage-specific distribution of high levels of genomic 5-hydroxymethylcytosine in mammalian development.

Methylation of cytosine is a DNA modification associated with gene repression. Recently, a novel cytosine modification, 5-hydroxymethylcytosine (5-hmC) has been discovered. Here we examine 5-hmC distribution during mammalian development and in cellular systems, and show that the developmental dynamics of 5-hmC are different from those of 5-methylcytosine (5-mC); in particular 5-hmC is enriched in embryonic contexts compared to adult tissues. A detectable 5-hmC signal appears in pre-implantation development starting at the zygote stage, where the paternal genome is subjected to a genome-wide hydroxylation of 5-mC, which precisely coincides with the loss of the 5-mC signal in the paternal pronucleus. Levels of 5-hmC are high in cells of the inner cell mass in blastocysts, and the modification colocalises with nestin-expressing cell populations in mouse post-implantation embryos. Compared to other adult mammalian organs, 5-hmC is strongly enriched in bone marrow and brain, wherein high 5-hmC content is a feature of both neuronal progenitors and post-mitotic neurons. We show that high levels of 5-hmC are not only present in mouse and human embryonic stem cells (ESCs) and lost during differentiation, as has been reported previously, but also reappear during the generation of induced pluripotent stem cells; thus 5-hmC enrichment correlates with a pluripotent cell state. Our findings suggest that apart from the cells of neuronal lineages, high levels of genomic 5-hmC are an epigenetic feature of embryonic cell populations and cellular pluri- and multi-lineage potency. To our knowledge, 5-hmC represents the first epigenetic modification of DNA discovered whose enrichment is so cell-type specific.