The gain-of-function allelebamAE470Kbypasses the essential requirement for BamD in β-barrel outer membrane protein assembly

The outer membrane (OM) of gram-negative bacteria confers innate resistance to toxins and antibiotics. Integral β-barrel outer membrane proteins (OMPs) function to establish and maintain the selective permeability of the OM. OMPs are assembled into the OM by the β-barrel assembly machine (BAM), which is composed of one OMP—BamA—and four lipoproteins—BamB, C, D, and E. BamB, C, and E can be removed individually with only minor effects on barrier function; however, depletion of either BamA or BamD causes a global defect in OMP assembly and results in cell death. We have identified a gain-of-function mutation,bamAE470K, that bypasses the requirement for BamD. AlthoughbamD::kanbamAE470Kcells exhibit growth and OM barrier defects, they assemble OMPs with surprising robustness. Our results demonstrate that BamD does not play a catalytic role in OMP assembly, but rather functions to regulate the activity of BamA.

Global defect topology in nematic liquid crystals

We give the global homotopy classification of nematic textures for a general domain with weak anchoring boundary conditions and arbitrary defect set in terms of twisted cohomology, and give an explicit computation for the case of knotted and linked defects in R 3 , showing that the distinct homotopy classes have a 1–1 correspondence with the first homology group of the branched double cover, branched over the disclination loops. We show further that the subset of those classes corresponding to elements of order 2 in this group has representatives that are planar and characterize the obstruction for other classes in terms of merons. The planar textures are a feature of the global defect topology that is not reflected in any local characterization. Finally, we describe how the global classification relates to recent experiments on nematic droplets and how elements of order 4 relate to the presence of τ lines in cholesterics.

Compensatory anti-inflammatory response syndrome

SummaryThe concept of ‘Compensatory anti-inflammatory response syndrome’ (CARS) was proposed in 1997 by Roger Bone (1941–1997) to qualify the consequences of the counter-regulatory mechanisms initiated to limit the overzealous inflammatory process in patients with infectious (sepsis) or non-infectious systemic inflammatory response syndrome (SIRS). One major consequence of CARS is the modification of the immune status that could favour the enhanced susceptibility of intensive care patients to nosocomial infections. Indeed, most animal ‘two-hit’ models illustrate an enhanced sensitivity to infection after a first insult. However, this observation is highly dependent on the experimental procedure. Numerous functions of circulating leukocytes are altered in sepsis and SIRS patients, as well as in animal models of sepsis or SIRS. However, this is rather a reprogramming of circulating leukocytes, since there is not a global defect of the immune cells functions. Furthermore, within tissues, leukocytes are rather primed or activated than immunosuppressed. Thus, CARS may be considered as an adapted compartmentalized response with the aim to silence some acute proinflammatory genes, and to maintain the possible expression of certain genes involved in the anti-infectious process.