Asymmetric division of adult stem cells generates one self-renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. A decline in stem cell function has been proposed to contribute to tissue aging, although the underlying mechanism is poorly understood. Here, we show that changes in the stem cell orientation with respect to the niche during aging contribute to the decline in spermatogenesis in Drosophila male germ line. Throughout the cell cycle, centrosomes in germ line stem cells (GSCs) are oriented within their niche and ensures asymmetric division. We found that GSCs containing misoriented centrosomes accumulate with age and that these GSCs are arrested or delayed in the cell cycle. The cell cycle arrest is transient, and GSCs appear to re-enter cell cycle upon correction of centrosome orientation. Based on these findings, we propose that cell cycle arrest associated with centrosome misorientation functions as a mechanism to ensure asymmetric stem cell division, and that the inability of stem cells to maintain correct orientation during aging contributes to the decline in spermatogenesis. We further show that some of misoriented GSCs likely originate from dedifferentiation of spermatogonia.

MutL homolog 3 (Mlh3) is a member of a family of proteins conserved during evolution and having dual roles in DNA mismatch repair and meiosis. The pathway in eukaryotes consists of the DNA-binding components, which are the homologs of the bacterial MutS protein (MSH 2 6), and the MutL homologs, which bind to the MutS homologs and are essential for the repair process. Three of the six homologs of MutS that function in these processes, Msh2, Msh3 and Msh6, are involved in the mismatch repair of mutations, frameshifts and replication errors, and two others, Msh4 and Msh5, have specific roles in meiosis. Of the four MutL homologs, Mlh1, Mlh3, Pms1 and Pms2, three are involved in mismatch repair and at least two, Pms2 and Mlh1, are essential for meiotic progression in both yeast and mice. To assess the role of Mlh3 in mammalian meiosis, we have generated and characterized Mlh3(-/-) mice. Here we show that Mlh3(-/-) mice are viable but sterile. Mlh3 is required for Mlh1 binding to meiotic chromosomes and localizes to meiotic chromosomes from the mid pachynema stage of prophase I. Mlh3(-/-) spermatocytes reach metaphase before succumbing to apoptosis, but oocytes fail to complete meiosis I after fertilization. Our results show that Mlh3 has an essential and distinct role in mammalian meiosis.

Quantum computation requires a continuous supply of rapidly initialized qubits for quantum error correction. Here, we demonstrate fast spin state initialization with near unity efficiency in a singly charged quantum dot by optically cooling an electron spin. The electron spin is successfully cooled from 5 to 0.06 K at a magnetic field of 0.88 T applied in Voigt geometry. The spin cooling rate is of order 10(9) s-1, which is set by the spontaneous decay rate of the excited state.

We report on the coherent optical excitation of electron spin polarization in the ground state of charged GaAs quantum dots via an intermediate charged exciton (trion) state. Coherent optical fields are used for the creation and detection of the Raman spin coherence between the spin ground states of the charged quantum dot. The measured spin decoherence time, which is likely limited by the nature of the spin ensemble, approaches 10 ns at zero field. We also show that the Raman spin coherence in the quantum beats is caused not only by the usual stimulated Raman interaction but also by simultaneous spontaneous radiative decay of either excited trion state to a coherent combination of the two spin states.

The data are consistent with a mechanochemical model in which a spatially extended GTP cap allows substantial shortening on the nanoscale, while still preventing complete catastrophe in most cases.