(2R,4R)-4-(2-Eth­oxy-2-oxoeth­yl)-2,6,6-trimeth­yl–2-oxo-1,3,6,2λ5-dioxaza­phospho­can-6-ium iodide

The title compound, C11H23NO5P+·I−, consists of an eight-membered cationic heterocyclic ring in a boat–chair conformation. The ring features a tetra­alkyl­ammonium N and a methyl­phospho­nate P atom. A –CH2(CO)OC2H5 ester side chain at the C adjacent to oxygen produces two chiral centers at that substituted C atom and the P atom, both of which were determined to have absolute R,R configurations. A previously determined racemic bromide analog has exactly the same ring but with a –C15H31 side chain. In that structure, both chiral centers show the same relative R/S,R/S configurations, but the ring in the bromide analog is in a boat conformation

tert-Butyl (2S)-2-{3-[(R)-bis­(tert-but­oxy­carbon­yl)amino]-2-oxopiperidin-1-yl}-3-methyl­butano­ate1

The title compound, C24H42N2O7, is a chiral lactam-constrained amino acid with a six-membered ring backbone and isopropyl and tert-butyl ester side chains. The conformation of the six-membered ring can be described as a half chair, with two CH2 C atoms lying 0.443 (1) and −0.310 (1) Å out of the best plane of the other four atoms (mean deviation = 0.042 Å). Both N atoms are sp 2 hybridized, lying 0.0413 (9) and 0.067 (1) Å out of the planes defined by the three C atoms bonded to them. The absolute configuration was determined, based on resonant scattering of light atoms in Cu Kα radiation

3-(Trimethyl­sil­yl)prop-2-ynyl p-toluene­sulfonate

In the title compound, C13H18O3SSi, the SO3 group displays a partial rotational (ca 50°) disorder about the C—S bond, with relative proportions 0.7744 (13):0.2256 (13). This disorder also forces the propynyl CH2 group to be disordered

Dibenzo[a,e]penta­cyclo­[12.2.1.16,9.02,13.05.10]octa­deca-2(13),5(10)-diene

In the title compound, C26H24, the central cyclo­octa­tetra­ene ring has a boat conformation, and the mol­ecule is saddle shaped. The seat is defined by the mean plane of the four-atom attachment points (r.m.s. deviation = 0.014 Å) of the two bicyclo­heptane substituents. These substituents comprise the pommel and cantle, with each mean plane defined by four atoms proximate to the seat (r.m.s. deviations = 0.001 and 0.000 Å). Relative to the seat, the pommel and cantle bend up 33.36 (5) and 34.22 (4)°, while the benzo units (flaps, r.m.s. deviations = 0.008 and 0.013 Å) bend down 33.48 (4) and 36.58 (4)°

25,26-Bis(propan-2-yl­idene)hepta­cyclo[20.2.1.110,13.02,21.03,8.09,14.015,20]hexa­cosa-2(21),3,5,7,9(14),11,15,17,19,23-deca­ene

In the title compound, C32H28, the central cyclo­octa­tetra­ene ring has a boat conformation, and the mol­ecule is saddle shaped. The seat is defined by the mean plane of the four-atom attachment points (r.m.s. deviation = 0.014 Å) of the two bicyclo­heptenyl substituents. These substituents comprise the pommel and cantle, with each mean plane defined by four atoms proximate to the seat (r.m.s. deviations = 0.002 and 0.004 Å). Relative to the seat, the pommel and cantle bend up 31.16 (4) and 29.40 (5)°, while the benzo units (flaps, r.m.s. deviations = 0.006 and 0.009 Å) bend down 36.75 (4) and 38.46 (4)°. The mean planes of the dimethyl­ethyl­idene units are almost perpendicular to the saddle seat, making dihedral angles 86.89 (4) and 88.01 (4)°

Microglia: neuroimmune-sensors of stress

Exposure to stressors disrupts homeostasis and results in the release of stress hormones including glucocorticoids, epinepherine and norepinepherine. Interestingly, stress also has profound affects on microglia, which are tissue-resident macrophages in the brain parenchyma. Microglia express a diverse array of receptors, which also allows them to respond to stress hormones derived from peripheral as well as central sources. Here, we review studies of how exposure to acute and chronic stressors alters the immunophenotype and function of microglia. Further, we examine a causal for stress hormones in these effects of stress on microglia. We propose that microglia serve as immunosensors of the stress response, which puts them in the unique position to sense and respond rapidly to alterations in homeostasis and integrate the neural response to threats.</p

Glucocorticoids mediate stress induction of the alarmin HMGB1 and reduction of the microglia checkpoint receptor CD200R1 in limbic brain structures

Exposure to stressors primes neuroinflammatory responses to subsequent immune challenges and stress-induced glucocorticoids (GCs) play a mediating role in this phenomenon of neuroinflammatory priming. Recent evidence also suggests that the alarmin high-mobility group&nbsp; box-1 (HMGB1) and the microglial checkpoint receptor CD200R1 serve as proximal mechanisms of stress-induced neuroinflammatory priming. However, it is unclear whether stress-induced GCs play a causal role in these proximal mechanisms of neuroinflammatory priming; this forms the focus of the present investigation. Here, we found that exposure to a severe acute stressor (inescapable tailshock) induced HMGB1 and reduced CD200R1 expression in limbic brain regions and pharmacological blockade of GC signaling (RU486) mitigated these effects of stress. To confirm these effects of RU486, adrenalectomy (ADX) with basal corticosterone (CORT) replacement was used to block the stress-induced increase in GCs as well as effects on HMGB1 and CD200R1. As with RU486, ADX mitigated the effects of stress on HMGB1 and CD200R1. Subsequently, exogenous CORT was administered to determine whether GCs are sufficient to recapitulate the effects of stress. Indeed, exogenous CORT induced expression of HMGB1 and reduced expression of CD200R1. In addition, exposure of primary microglia to CORT also recapitulated the effects of stress on CD200R1 suggesting that CORT acts directly on microglia to reduce expression of CD200R1. Taken together, these findings suggest that GCs mediate the effects of stress on these proximal mechanisms of neuroinflammatory priming.</p

(5RS,10SR,15RS)-Trimethyl­truxene1

The title mol­ecule, C30H24, was prepared as a possible precursor to buckminsterfullerene cages. The two enanti­omers adopt the anti configuration, with one S/R and two R/S methyl groups, one anti to the other two. The truxene framework is slightly non-planar: with respect to the central six-ring mean plane, the three methyl C atoms are 1.377 (3), −1.475 (3) and 1.515 (3) Å distant, whereas the respective proximate peripheral six-ring mean planes make dihedral angles of 6.27 (6), 3.45 (7) and −7.37 (7)°