Galectin-3 promotes noncanonical inflammasome activation through intracellular binding to lipopolysaccharide glycans

Cytosolic lipopolysaccharides (LPSs) bind directly to caspase-4/5/11 through their lipid A moiety, inducing inflammatory caspase oligomerization and activation, which is identified as the noncanonical inflammasome pathway. Galectins, β-galactoside–binding proteins, bind to various gram-negative bacterial LPS, which display β-galactoside–containing polysaccharide chains. Galectins are mainly present intracellularly, but their interactions with cytosolic microbial glycans have not been investigated. We report that in cell-free systems, galectin-3 augments the LPS-induced assembly of caspase-4/11 oligomers, leading to increased caspase-4/11 activation. Its carboxyl-terminal carbohydrate-recognition domain is essential for this effect, and its N-terminal domain, which contributes to the self-association property of the protein, is also critical, suggesting that this promoting effect is dependent on the functional multivalency of galectin-3. Moreover, galectin-3 enhances intracellular LPS-induced caspase-4/11 oligomerization and activation, as well as gasdermin D cleavage in human embryonic kidney (HEK) 293T cells, and it additionally promotes interleukin-1β production and pyroptotic death in macrophages. Galectin-3 also promotes caspase-11 activation and gasdermin D cleavage in macrophages treated with outer membrane vesicles, which are known to be taken up by cells and release LPSs into the cytosol. Coimmunoprecipitation confirmed that galectin-3 associates with caspase-11 after intracellular delivery of LPSs. Immunofluorescence staining revealed colocalization of LPSs, galectin-3, and caspase-11 independent of host N-glycans. Thus, we conclude that galectin-3 amplifies caspase-4/11 oligomerization and activation through LPS glycan binding, resulting in more intense pyroptosis—a critical mechanism of host resistance against bacterial infection that may provide opportunities for new therapeutic interventions.

On negative association of some finite point processes on general state spaces

We study negative association for mixed sampled point processes and show that negative association holds for such processes if a random number of their points fulfils the ultra log-concave (ULC) property. We connect the negative association property of point processes with directionally convex dependence ordering, and show some consequences of this property for mixed sampled and determinantal point processes. Some applications illustrate the general theory.

Association, property, territory: What is at stake in immigration?

It is often claimed that states have territorial rights, and that these rights include the right to exclude people who seek admission to their territory. In this paper I will examine whether the most defensible account of territorial rights can provide support to the right to exclude. I will discuss three types of theories of territorial rights. The first account links the right of states to exclude to the prior right of individuals to freedom of association, which is said to include the right not to associate and to dissociate. The second is a Lockean theory that grounds the territorial rights of states, and hence their right to exclude, in the prior right of individuals to private property in the land that constitutes the territory of the state. I argue that these accounts have independently implausible implications, regardless of their implications for the immigration debate. The third account is a Kantian theory that bases the territorial jurisdiction of states on individuals? duty to create, sustain and submit themselves to a shared system of law that is a necessary condition of guaranteeing their rights and of discharging their duties towards one another. I will argue that the Kantian account is superior to its current alternatives. However, I also suggest that it cannot ground a broad right to exclude.

5. Deprivations of life and liberty

‘Deprivations of life and liberty’ considers the rights to life and liberty, which may be limited through legal restrictions designed to protect a defined legitimate objective. The human rights approach starts from a presumption that we all have rights to liberty, freedom of expression, belief, assembly, association, property, and fair trial. Any restriction on these rights has to be justified as proportionate to the aims pursued by the restriction according to a four-stage schema developed in human rights law. Is the right to life absolute? When is the detention of an individual lawful?

Balance between Distinct HP1 Family Proteins Controls Heterochromatin Assembly in Fission Yeast

ABSTRACT Heterochromatin protein 1 (HP1) is a conserved chromosomal protein with important roles in chromatin packaging and gene silencing. In fission yeast, two HP1 family proteins, Swi6 and Chp2, are involved in transcriptional silencing at heterochromatic regions, but how they function and whether they act cooperatively or differentially in heterochromatin assembly remain elusive. Here, we show that both Swi6 and Chp2 are required for the assembly of fully repressive heterochromatin, in which they play distinct, nonoverlapping roles. Swi6 is expressed abundantly and plays a dose-dependent role in forming a repressive structure through its self-association property. In contrast, Chp2, expressed at a lower level, does not show a simple dose-dependent repressive activity. However, it contributes to the recruitment of chromatin-modulating factors Clr3 and Epe1 and possesses a novel ability to bind the chromatin-enriched nuclear subfraction that is closely linked with its silencing function. Finally, we demonstrate that a proper balance between Swi6 and Chp2 is critical for heterochromatin assembly. Our findings provide novel insight into the distinct and cooperative functions of multiple HP1 family proteins in the formation of higher-order chromatin structure.

Correlated Matroids

Semple and Welsh [5] introduced the concept of correlated matroids, which relate to conjectures by Grimmett and Winkler [2], and Pemantle [4], respectively, that the uniformly random forest and the uniformly random connected subgraph of a finite graph have the edge-negative-association property. In this paper, we extend results of Semple and Welsh, and show that the Grimmett and Winkler, and Pemantle conjectures are equivalent to statements about correlated graphic matroids. We also answer some open questions raised in [5] regarding correlated matroids, and in particular show that the 2-sum of correlated matroids is correlated.

Negative Correlation in Graphs and Matroids

The following two conjectures arose in the work of Grimmett and Winkler, and Pemantle: the uniformly random forest F and the uniformly random connected subgraph C of a finite graph G have the edge-negative association property. In other words, for all distinct edges e and f of G, the probability that F (respectively, C) contains e conditioned on containing f is less than or equal to the probability that F (respectively, C) contains e. Grimmett and Winkler showed that the first conjecture is true for all simple graphs on 8 vertices and all graphs on 9 vertices with at most 18 edges. In this paper, we describe an infinite, nontrivial class of graphs and matroids for which a generalized version of both conjectures holds.