COSA-1 reveals robust homeostasis and separable licensing and reinforcement steps governing meiotic crossovers.

Crossovers (COs) between homologous chromosomes ensure their faithful segregation during meiosis. We identify C. elegans COSA-1, a cyclin-related protein conserved in metazoa, as a key component required to convert meiotic double-strand breaks (DSBs) into COs. During late meiotic prophase, COSA-1 localizes to foci that correspond to the single CO site on each homolog pair and indicate sites of eventual concentration of other conserved CO proteins. Chromosomes gain and lose competence to load CO proteins during meiotic progression, with competence to load COSA-1 requiring prior licensing. Our data further suggest a self-reinforcing mechanism maintaining CO designation. Modeling of a nonlinear dose-response relationship between IR-induced DSBs and COSA-1 foci reveals efficient conversion of DSBs into COs when DSBs are limiting and a robust capacity to limit cytologically differentiated CO sites when DSBs are in excess. COSA-1 foci serve as a unique live cell readout for investigating CO formation and CO interference.

The phenomenology of optically pumped (13)C NMR in diamond at 7.05T: Room temperature polarization, orientation dependence, and the effect of defect concentration on polarization dynamics.

Room temperature optical illumination of NV- imbibed single crystal diamonds with a 532 nm laser produces (13)C polarization enhancements up to 200 times greater than that of the thermal equilibrium value at 7.05 T. We report high field NV- mediated (13)C polarization as a function of the number and type (NV- and P1) of defects in commercially available diamonds. Surprisingly, both positive and negative (13)C polarizations are observed depending on the orientation of the crystal with respect to the external magnetic field and the electric field vector of the optical illumination. The data reported herein cannot be explained by a previously proposed mechanism.

A requirement for ERK-dependent Dicer phosphorylation in coordinating oocyte-to-embryo transition in C. elegans.

Signaling pathways and small RNAs direct diverse cellular events, but few examples are known of defined signaling pathways directly regulating small RNA biogenesis. We show that ERK phosphorylates Dicer on two conserved residues in its RNase IIIb and double-stranded RNA (dsRNA)-binding domains and that phosphorylation of these residues is necessary and sufficient to trigger Dicer's nuclear translocation in worms, mice, and human cells. Phosphorylation of Dicer on either site inhibits Dicer function in the female germline and dampens small RNA repertoire. Our data demonstrate that ERK phosphorylates and inhibits Dicer during meiosis I for oogenesis to proceed normally in Caenorhabditis elegans and that this inhibition is released before fertilization for embryogenesis to proceed normally. The conserved Dicer residues, their phosphorylation by ERK, and the consequences of the resulting modifications implicate an ERK-Dicer nexus as a fundamental component of the oocyte-to-embryo transition and an underlying mechanism coupling extracellular cues to small RNA production.

DAF-2 and ERK couple nutrient availability to meiotic progression during Caenorhabditis elegans oogenesis.

Coupling the production of mature gametes and fertilized zygotes to favorable nutritional conditions improves reproductive success. In invertebrates, the proliferation of female germline stem cells is regulated by nutritional status. However, in mammals, the number of female germline stem cells is set early in development, with oocytes progressing through meiosis later in life. Mechanisms that couple later steps of oogenesis to environmental conditions remain largely undefined. We show that, in the presence of food, the DAF-2 insulin-like receptor signals through the RAS-ERK pathway to drive meiotic prophase I progression and oogenesis; in the absence of food, the resultant inactivation of insulin-like signaling leads to downregulation of the RAS-ERK pathway, and oogenesis is stalled. Thus, the insulin-like signaling pathway couples nutrient sensing to meiotic I progression and oocyte production in C. elegans, ensuring that oocytes are only produced under conditions favorable for the survival of the resulting zygotes.

Interaction with Shc prevents aberrant Erk activation in the absence of extracellular stimuli.

Control mechanisms that prevent aberrant signaling are necessary to maintain cellular homeostasis. We describe a new mechanism by which the adaptor protein Shc directly binds the MAP kinase Erk, thus preventing its activation in the absence of extracellular stimuli. The Shc-Erk complex restricts Erk nuclear translocation, restraining Erk-dependent transcription of genes, including those responsible for oncogenic growth. The complex forms through unique binding sites on both the Shc PTB domain and the N-terminal lobe of Erk. Upon receptor tyrosine kinase stimulation, a conformational change within Shc-induced through interaction with the phosphorylated receptor-releases Erk, allowing it to fulfill its role in signaling. Thus, in addition to its established role in promoting MAP kinase signaling in stimulated cells, Shc negatively regulates Erk activation in the absence of growth factors and thus could be considered a tumor suppressor in human cells.

Do hockey players need aerobic fitness? Relation between VO2max and fatigue during high-intensity intermittent ice skating.

The primary objective of this study was to assess the relationship between aerobic capacity, as measured by the VO(2)max test, and recovery from high-intensity intermittent exercise. Eleven female collegiate hockey players agreed to participate. Subjects skated 5 1-lap intervals around the hockey rink at maximal intensity with a 30-second recovery period between skates. The VO(2)max test was performed on a motor-driven treadmill after a modified Bruce protocol. A fatigue index was calculated by measuring the total increase in skate time from trial 1 to trial 5. This fatigue index was then correlated to VO(2)max. This correlation coefficient (-0.422) was not significant (p > 0.05) and indicated that only 17.8% of the variance in VO(2)max could be explained by the fatigue index. It was concluded that ability to recover from high-intensity intermittent exercise is not related to aerobic capacity. Coaches and trainers probably do not need to include aerobic training in their practices, because the high-intensity interval training commonly seen in hockey training also improves aerobic capacity, as reflected in the high VO(2)max values of these subjects.