Five subunits are required for reconstitution of the cleavage and polyadenylation activities of Saccharomyces cerevisiae cleavage factor I

Cleavage and polyadenylation of mRNA 3′ ends in Saccharomyces cerevisiae requires several factors, one of which is cleavage factor I (CF I). Purification of CF I activity from yeast extract has implicated numerous proteins as functioning in both cleavage and/or polyadenylation. Through reconstitution of active CF I from separately expressed and purified proteins, we show that CF I contains five subunits, Rna14, Rna15, Pcf11, Clp1, and Hrp1. These five are necessary and sufficient for reconstitution of cleavage activity in vitro when mixed with CF II, and for specific polyadenylation when mixed with polyadenylation factor I, purified poly(A) polymerase, and poly(A) binding protein. Analysis of the individual protein–protein interactions supports an architectural model for CF I in which Pcf11 simultaneously interacts with Rna14, Rna15, and Clp1, whereas Rna14 bridges Rna15 and Hrp1.

Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.

A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a recently synthesized structural class has been characterized. L-163,191 releases GH from rat pituitary cells in culture with EC50 = 1.3 +/- 0.09 nM and is mechanistically indistinguishable from the GH-releasing peptide GHRP-6 and the prototypical nonpeptide GH secretagogue L-692,429 but clearly distinguishable from the natural GH secretagogue, GH-releasing hormone. L-163,191 elevates GH in dogs after oral doses as low as 0.125 mg/kg and was shown to be specific in its release of GH without significant effect on plasma levels of aldosterone, luteinizing hormone, thyroxine, and prolactin after oral administration of 1 mg/kg. Only modest increases in cortisol were observed. Based on these properties, L-163,191 has been selected for clinical studies.

An allosteric switch controls the procoagulant and anticoagulant activities of thrombin.

Thrombin is an allosteric enzyme existing in two forms, slow and fast, that differ widely in their specificities toward synthetic and natural amide substrates. The two forms are significantly populated in vivo, and the allosteric equilibrium can be affected by the binding of effectors and natural substrates. The fast form is procoagulant because it cleaves fibrinogen with higher specificity; the slow form is anticoagulant because it cleaves protein C with higher specificity. Binding of thrombomodulin inhibits cleavage of fibrinogen by the fast form and promotes cleavage of protein C by the slow form. The allosteric properties of thrombin, which has targeted two distinct conformational states toward its two fundamental and competing roles in hemostasis, are paradigmatic of a molecular strategy that is likely to be exploited by other proteases in the blood coagulation cascade.

The Exploration and Development of Alternative Management Strategies for Mining and Recreational Activities Atop Mount Antero and Mount White; Chaffee County, Colorado

The Mount Antero/White area is a popular prospecting area. Recent expansions in the recreation economy is drawing more visitors to the area. Consequently, visitors may be placing unsustainable pressures on the landscape. In order to help rectify this, the legal, ecological, geologic, aesthetic, recreational, historic, social, and economic character of the Antero/White area has been identified. Four feasible management alternatives have also been recognized. They are a) take no new management actions, b) prohibit motorized activities in the area, c) develop a mineralogical park, and d) a combination of options b and c. Option C has been defended, as it best balances the desires of area users with the underlying ecological and geological character of the area.

Structured Sports and Physical Activities: Their Critical Role

Even though one recognizes the physical and psychological kindness of h more and more involvement of the children to the physical and sporty activities, these programs seem more and more inaccessible to some. This article underlines the importance school déprogrammes centered on structured physical and sporty activities. In the setting of a recent survey, one asked youngsters to 5th year to take in note all their activities (as diary calendar) during two days of consecutive week. L·s children that participated in structured physical and sporty activities before and after the hours class sembkient to pull a lot more phisir of their day that those that didn't participate in these activities. Besides, seuk the young that took to structured physical and sporty activities reached the rates recommended of daily physical activity. The article proposes to the school administrators, to the parents, to the children and to the collectivities various measures encouraging the adoption of additional programs centered on the physical and sporty activities in school environment.

Applied Research Sport Experiences, Milestones, and Educational Activities Associated With High-Performance Coaches' Development

What experiences are needed to become a high-performance coach? The present study addressed this question through structured retrospective quantitative interviews with 10 team- and 9 individual-sport coaches at the Canadian interuniversity-sport level. Minimum amounts of certain experiences were deemed necessary but not sufficient to become a high-performance coach (e.g., playing the sport they now coach and interaction with a mentor coach for all coaches, leadership opportunities as athletes for team-sport coaches only). Although coaches reported varying amounts of these necessary experiences, general stages of high-performance coach development were traced. Findings serve to identify and support potential high-performance coaches and increase the effectiveness of formal coaching-education programs.