Attenuation of cGAS‐STING signaling is mediated by a p62/SQSTM1‐dependent autophagy pathway activated by TBK1

Negative regulation of immune pathways is essential to achieve resolution of immune responses and to avoid excess inflammation. DNA stimulates type I IFN expression through the DNA sensor cGAS, the second messenger cGAMP, and the adaptor molecule STING. Here, we report that STING degradation following activation of the pathway occurs through autophagy and is mediated by p62/SQSTM1, which is phosphorylated by TBK1 to direct ubiquitinated STING to autophagosomes. Degradation of STING was impaired in p62‐deficient cells, which responded with elevated IFN production to foreign DNA and DNA pathogens. In the absence of p62, STING failed to traffic to autophagy‐associated vesicles. Thus, DNA sensing induces the cGAS‐STING pathway to activate TBK1, which phosphorylates IRF3 to induce IFN expression, but also phosphorylates p62 to stimulate STING degradation and attenuation of the response.     

Association patterns and kinship in female reindeer (Rangifer tarandus) during rut

Non-random association of females has been reported in many social species, with kinship being the main mechanism in shaping these associations. Understanding the patterns of association during rut is particularly important in polygynous animals, as this may have implications for inbreeding vulnerability and genetic structuring of populations. However, these patterns are highly dynamic and may be influenced by the population sex ratio and male age structure. We examined females' association in reindeer (Rangifer tarandus), a highly polygynous ungulate, to determine whether genetically related females associate more often than non-kin during rut and whether this association was influenced by the aforementioned factors. During three rutting seasons the male age structure and the sex ratio of the herd was manipulated: two extremely female biased sex ratios, one with only adult males and one with only young males, whereas the third being closer to a more even sex ratio and male age structure. We found that genetic relatedness influenced female association in the mixed male age group, but not in the adult and young male age groups. Highly related females (relatedness ??0.5) associated more closely than unrelated females. Further, period of the rut as well as male age structure and sex ratio had a significant effect on female association. Our study suggests that the female reindeer association during rut is not only influenced by preference for kin but also by male?Cmale competition and male age as well.     

Macrophage-lymphocyte clusters in the immune response to soluble protein antigen in vitro. IV. Synergy of lymphocytes in the formation of clusters.

T-lymphocyte-enriched lymph node lymphocytes from guinea pigs immunized with Mycobacterium tuberculosis produce clusters with macrophages when cultivated on monolayers of syngeneic purified protein derivative of tuberculin (PPD)-pulsed peritoneal macrophages. The clusters consist of a macrophage with a central lymphocyte attached to it, and several peripheral lymphocytes attached to the central one. By mechanical manipulation immune lymphocytes incubated on monolayers of PPD-pulsed macrophages were separated into those which adhered firmly to the macrophages after 4 hr of culture and those which did not adhere. While neither of the two populations was able to produce significant numbers of clusters alone, they did so in combination. The number of macrophage-lymphocyte clusters which are produced in a culture depends not only on the absolute number of immune lymphocytes in the culture, but also on the concentration of lymphocytes per area of the macrophage monolayer, with high concentrations resulting in high numbers of clusters. Autoradiographic studies showed that the DNA-synthesizing lymphocytes physically associated with macrophages were located mainly inside the clusters in cultures with high concentrations of lymphocytes but mainly outside the clusters in cultures with low concentrations of lymphocytes.     

Reproductive strategy of two deep-sea scalpellid barnacles (Crustacea: Cirripedia: Thoracica) associated with decapods and pycnogonids and the first description of a penis in scalpellid dwarf males

We investigated the sexual system in two pedunculate barnacles of the family Scalpellidae. Both inhabit deep water and are attached to mobile arthropod hosts. Verum brachiumcancri was attached to the majid crab Rochinia hertwigi, and Weltnerium nymphocola to the pycnogonidan sea spider Boreonymphon rubrum. Both barnacles have separate sexes and females almost always carry two dwarf males that are almost fully embedded in a pair of symmetrically situated receptacles inside the rim of the mantle cavity. The dwarf males of V. brachiumcancri have a complex penile structure extending into the female mantle cavity. This is the first time a copulatory structure has been described in detail for a dwarf male of a scalpellid barnacle. Both species lack free nauplii and their larvae are released as cyprids; the brood size is small. This is probably an adaptation for settling close to the parent population. We compare reproductive strategies among scalpellids and suggest that the present males are highly specialized and that the females are allocating resources to few offspring.     

Human exonuclease 1 (EXO1) activity characterization and its function on flap structures

Human exonuclease 1 (EXO1) is involved in multiple DNA metabolism processes, including DNA repair and replication. Most of the fundamental roles of EXO1 have been described in yeast. Here, we report a biochemical characterization of human full-length EXO1. Prior to assay EXO1 on different DNA flap structures, we determined factors essential for the thermodynamic stability of EXO1. We show that enzymatic activity and stability of EXO1 on DNA is modulated by temperature. By characterization of EXO1 flap activity using various DNA flap substrates, we show that EXO1 has a strong capacity for degrading double stranded DNA and has a modest endonuclease or 5′ flap activity. Furthermore, we report novel mechanistic insights into the processing of flap structures, showing that EXO1 preferentially cleaves one nucleotide inwards in a double stranded region of a forked and nicked DNA flap substrates, suggesting a possible role of EXO1 in strand displacement.     

How the leopard got its spots: a phylogenetic view of the evolution of felid coat patterns

The current theory of felid coat pattern evolution proposes that the primitive pattern is one of relatively large spots that break down into smaller spots (here denoted flecks) and rosettes while at the same time leading to various striped patterns as sidelines. We have coded the coat patterns of felids into uniform, flecks, rosettes, vertical stripes, small blotches and blotches and show by mapping these character states onto phylogenies of the family that the current theory is flawed. Instead, the primitive pattern appears to be flecks and it is from this type that nearly all other types have developed. The robustness of this hypothesis is shown by the fact that it remains unchanged regardless of which of several quite different, competing phylogenies of the family is used. The pattern of transformations reconstructed is not predicted by current theories of pattern formation and we suggest that modellers pay closer attention to the phylogenetic histories of the features that they model.     

Effect of Energy Metabolism on Protein Motility in the Bacterial Outer Membrane

We demonstrate the energy dependence of the motion of a porin, the λ-receptor, in the outer membrane of living Escherichia coli by single molecule investigations. By poisoning the bacteria with arsenate and azide, the bacterial energy metabolism was stopped. The motility of individual λ-receptors significantly and rapidly decreased upon energy depletion. We suggest two different causes for the ceased motility upon comprised energy metabolism: One possible cause is that the cell uses energy to actively wiggle its proteins, this energy being one order-of-magnitude larger than thermal energy. Another possible cause is an induced change in the connection between the λ-receptor and the membrane structure, for instance by a stiffening of part of the membrane structure. Treatment of the cells with ampicillin, which directly targets the bacterial cell wall by inhibiting cross-linking of the peptidoglycan layer, had an effect similar to energy depletion and the motility of the λ-receptor significantly decreased. Since the λ-receptor is closely linked to the peptidoglycan layer, we propose that λ-receptor motility is directly coupled to the constant and dynamic energy-consuming reconstruction of the peptidoglycan layer. The result of this motion could be to facilitate transport of maltose-dextrins through the porin.