We present an overview of galaxy evolution across cosmic time in the Illustris Simulation. Illustris is an N-body/hydrodynamical simulation that evolves 2 × 1820 3 resolution elements in a (106.5 Mpc)3 box from cosmological initial conditions down to z = 0 using the AREPO moving-mesh code. The simulation uses a state-of-the-art set of physical models for galaxy formation that was tuned to reproduce the z = 0 stellar mass function and the history of the cosmic star-formation rate density. We find that Illustris successfully reproduces a plethora of observations of galaxy populations at various redshifts, for which no tuning was performed, and provide predictions for future observations. In particular, we discuss (a) the buildup of galactic mass, showing stellar mass functions and the relations between stellar mass and halo mass from z = 7 to z = 0, (b) galaxy number density profiles around massive central galaxies out to z = 4, (c) the gas and total baryon content of both galaxies and their halos for different redshifts, and as a function of mass and radius, and (d) the evolution of galaxy specific star-formation rates up to z = 8. In addition, we (i) present a qualitative analysis of galaxy morphologies from z = 5 to z = 0, for the stellar as well as the gaseous components, and their appearance in HST mock observations, (ii) follow galaxies selected at z = 2 to their z = 0 descendants, and quantify their growth and merger histories, and (iii) track massive z = 0 galaxies to high redshift and study their joint evolution in star-formation activity and compactness. We conclude with a discussion of several disagreements with observations, and lay out possible directions for future research.

We have constructed merger trees for galaxies in the Illustris Simulation by directly tracking the baryonic content of subhalos. These merger trees are used to calculate the galaxy-galaxy merger rate as a function of descendant stellar mass, progenitor stellar mass ratio, and redshift. We demonstrate that the most appropriate definition for the mass ratio of a galaxy-galaxy merger consists in taking both progenitor masses at the time when the secondary progenitor reaches its maximum stellar mass. Additionally, we avoid effects from 'orphaned' galaxies by allowing some objects to 'skip' a snapshot when finding a descendant, and by only considering mergers which show a well-defined 'infall' moment. Adopting these definitions, we obtain well-converged predictions for the galaxy-galaxy merger rate with the following main features, which are qualitatively similar to the halo-halo merger rate except for the last one: a strong correlation with redshift that evolves as ∼ (1 + z) 2.4−2.8 , a power law with respect to mass ratio, and an increasing dependence on descendant stellar mass, which steepens significantly for descendant stellar masses greater than ∼ 2 × 10 11 M . These trends are consistent with observational constraints for medium-sized galaxies (M * 10 10 M ), but in tension with some recent observations of the close pair fraction for massive galaxies (M * 10 11 M ), which report a nearly constant or decreasing evolution with redshift. Finally, we provide a fitting function for the galaxy-galaxy merger rate which is accurate over a wide range of stellar masses, progenitor mass ratios, and redshifts.

The insect immune deficiency (IMD) pathway resembles the tumour necrosis factor receptor network in mammals and senses diaminopimelic-type peptidoglycans present in Gram-negative bacteria. Whether unidentified chemical moieties activate the IMD signalling cascade remains unknown. Here, we show that infection-derived lipids 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and 1-palmitoyl-2-oleoyl diacylglycerol (PODAG) stimulate the IMD pathway of ticks. The tick IMD network protects against colonization by three distinct bacteria, that is the Lyme disease spirochete Borrelia burgdorferi and the rickettsial agents Anaplasma phagocytophilum and A. marginale. Cell signalling ensues in the absence of transmembrane peptidoglycan recognition proteins and the adaptor molecules Fas-associated protein with a death domain (FADD) and IMD. Conversely, biochemical interactions occur between x-linked inhibitor of apoptosis protein (XIAP), an E3 ubiquitin ligase, and the E2 conjugating enzyme Bendless. We propose the existence of two functionally distinct IMD networks, one in insects and another in ticks.

SUMMARY Toll-like receptors (TLRs) activate distinct, yet overlapping sets of signaling molecules, leading to inflammatory responses to pathogens. Toll-IL-1R (TIR) domains, present in all TLRs and TLR adapters, mediate protein interactions downstream of activated TLRs. A peptide library derived from TLR2 TIR was screened for inhibition of TLR2 signaling. Cell-permeable peptides derived from the D helix and the segment immediately N terminal to TLR2 TIR domain potently inhibited TLR2-mediated cytokine production. The D helix peptide, 2R9, also potently inhibited TLR4, TLR7, and TLR9, but not TLR3 or TNF-α signaling. Cell imaging, co-immunoprecipitation, and in vitro studies demonstrated that 2R9 preferentially targets TIRAP. 2R9 diminished systemic cytokine responses elicited in vivo by synthetic TLR2 and TLR7 agonists; it inhibited activation of macrophages infected with influenza strain A/PR/8/34 (PR8) and significantly improved survival of PR8-infected mice. Thus, 2R9 represents a TLR-targeting agent that blocks protein interactions downstream of activated TLRs.

The Toll/IL-1 receptor (TIR) domains are crucial signaling modules during innate immune responses involving the Toll-like receptors (TLRs) and IL-1 receptor (IL-1R). Myeloid differential factor 88 (MyD88) is a central TIR domain-containing adapter molecule responsible for nearly all TLR-mediated signaling and is targeted by a TIR domain-containing protein C (TcpC) from virulent uropathogenic Escherichia coli, a common human pathogen. The mechanism of such molecular antagonism has remained elusive. We present the crystal structure of the MyD88 TIR domain with distinct loop conformations that underscore the functional specialization of the adapter, receptor, and microbial TIR domains. Our structural analyses shed light on the genetic mutations at these loops as well as the Poc site. We demonstrate that TcpC directly associates with MyD88 and TLR4 through its predicted DD and BB loops to impair the TLR-induced cytokine induction. Furthermore, NMR titration experiments identify the unique CD, DE, and EE loops from MyD88 at the TcpC-interacting surface, suggesting that TcpC specifically engages these MyD88 structural elements for immune suppression. These findings thus provide a molecular basis for the subversion of TLR signaling by the uropathogenic E. coli virulence factor TcpC and furnish a framework for the design of novel therapeutic agents that modulate immune activation.innate immune cells | bacterial pathogens