The effect of aging on rat liver regeneration

Summary The effect of age on hepatocyte mensuration and mitotic activity 48 h after partial hepatectomy was investigated in rats. Both age and partial hepatectomy had significant effects upon hepatocyte counts per microscopic field. The number of hepatocytes per microscopic field declined with age in the control groups of different advancing ages and in the experimental groups of advancing ages. There was essentially no mitotic activity in the livers of the control groups. However, mitotic counts were greatly increased in livers from those animals that were partially hepatectomized; the increase in mitotic activity in the 13-month-old animals was double over that observed in both the very young and the very old.Acknowledgment. This research was supported in part by an Eastern Virginia Medical School Biomedical Research Development Fund. The investigators acknowledge the Gerontology Research Center, NIA, Baltimore, Maryland for their support.     

A single type of progenitor cell maintains normal epidermis

According to the current model of adult epidermal homeostasis, skin tissue is maintained by two discrete populations of progenitor cells: self-renewing stem cells; and their progeny, known as transit amplifying cells, which differentiate after several rounds of cell division. By making use of inducible genetic labelling, we have tracked the fate of a representative sample of progenitor cells in mouse tail epidermis at single-cell resolution in vivo at time intervals up to one year. Here we show that clone-size distributions are consistent with a new model of homeostasis involving only one type of progenitor cell. These cells are found to undergo both symmetric and asymmetric division at rates that ensure epidermal homeostasis. The results raise important questions about the potential role of stem cells on tissue maintenance in vivo.     

The APOBEC-2 crystal structure and functional implications for the deaminase AID

APOBEC-2 (APO2) belongs to the family of apolipoprotein B messenger RNA-editing enzyme catalytic (APOBEC) polypeptides, which deaminates mRNA and single-stranded DNA. Different APOBEC members use the same deamination activity to achieve diverse human biological functions. Deamination by an APOBEC protein called activation-induced cytidine deaminase (AID) is critical for generating high-affinity antibodies, and deamination by APOBEC-3 proteins can inhibit retrotransposons and the replication of retroviruses such as human immunodeficiency virus and hepatitis B virus. Here we report the crystal structure of APO2. APO2 forms a rod-shaped tetramer that differs markedly from the square-shaped tetramer of the free nucleotide cytidine deaminase, with which APOBEC proteins share considerable sequence homology. In APO2, two long alpha-helices of a monomer structure prevent the formation of a square-shaped tetramer and facilitate formation of the rod-shaped tetramer via head-to-head interactions of two APO2 dimers. Extensive sequence homology among APOBEC family members allows us to test APO2 structure-based predictions using AID. We show that AID deamination activity is impaired by mutations predicted to interfere with oligomerization and substrate access. The structure suggests how mutations in patients with hyper-IgM-2 syndrome inactivate AID, resulting in defective antibody maturation.