the identity of the turnover-limiting step will depend upon the relative olefin and hydrogen concentrations. Neither of these rate constants is particularly large in comparison to other f-element catalysts. Thus, hydrogenolysis is turnover-limiting in the analogous mechanism for (Cp,2LuH)2-catalyzed hydrogenation of 1-hexene, and k2 = 7.7 X 101 23 M"1 s'1 (&t ÍOMÓ3 M~* s"1).1011 Olefin addition is turnover-limiting for the corresponding hydrogenation of cyclohexene and ~2.3 X 10"2 M"1 s'1.10"1 The present results show that k{ is sterically very sensitive, and the simple transposition of OCH(?-Bu)2 -* O-f-Bu affects a ca. 103 increase in kx. Our earlier results12 show that k2 is sensitive to the electrophilicity at the metal center (which is depressed by OR introduction) and the Th-C bond enthalpy. As judged by variation in OR, k2 is (not surprisingly) sterically rather insensitive. The greater hydrogenolytic reactivity of U-C bonds vis-á-vis Th-C bonds apparently reflects electronic factors that do not dominate An-H olefin insertion chemistry.

Interleukin 6 (IL-6) has a broad effect on cells of the immune system and those not of the immune system and often displays hormone-like characteristics that affect homeostatic processes. IL-6 has context-dependent pro- and anti-inflammatory properties and is now regarded as a prominent target for clinical intervention. However, the signaling cassette that controls the activity of IL-6 is complicated, and distinct intervention strategies can inhibit this pathway. Clinical experience with antagonists of IL-6 has raised new questions about how and when to block this cytokine to improve disease outcome and patient wellbeing. Here we discuss the effect of IL-6 on innate and adaptive immunity and the possible advantages of various antagonists of IL-6 and consider how the immunobiology of IL-6 may inform clinical decisions.

No abstract

Molecular recognition events in solution are affected by many different factors that have hampered the development of an understanding of intermolecular interactions at a quantitative level. Our tendency is to partition these effects into discrete phenomenological fields that are classified, named, and divorced: aromatic interactions, cation-pi interactions, CH-O hydrogen bonds, short strong hydrogen bonds, and hydrophobic interactions to name a few.1 To progress in the field, we need to develop an integrated quantitative appreciation of the relative magnitudes of all of the different effects that might influence the molecular recognition behavior of a given system. In an effort to navigate undergraduates through the vast and sometimes contradictory literature on the subject, I have developed an approach that treats theoretical ideas and experimental observations about intermolecular interactions in the gas phase, the solid state, and solution from a single simplistic viewpoint. The key features are outlined here, and although many of the ideas will be familiar, the aim is to provide a semiquantitative thermodynamic ranking of these effects in solution at room temperature.

Interleukin 10 (IL-10) has a prominent function in regulating the balance between protective and pathological T cell responses. Consistent with that activity, many sources of this cytokine are found in vivo, including from myeloid cells and a variety of T cell subsets. However, although there are many pathways that regulate innate production of IL-10, the factors that govern its synthesis by the adaptive response are poorly understood. Here we report that IL-27 and IL-6 induced T helper type 1 and type 2 cells, as well as T helper cells that produce IL-17, to secrete IL-10. This effect was dependent on the transcription factors STAT1 and STAT3 for IL-27 and on STAT3 for IL-6. Our studies identify a previously unknown pathway that allows the immune system to temper inflammatory responses.