Since the early 2000s, a revival of a felid relationship for barbourofeline sabretooths has become popular due to recent discoveries of fragmentary fossils from Africa. According to this view, barbourofelines trace their common ancestor with felids through shared similarities in dental morphology going back to the early Miocene of Africa and Europe. However, whether or not such an idea is represented in the basicranial morphology, a conservative area of high importance in family-level relationships, is yet to be tested. A nearly complete skull of Oriensmilus liupanensis gen. and sp. nov. from the middle Miocene Tongxin Basin of northern China represents the most primitive known barbourofeline with an intact basicranial region, affording an opportunity to re-examine the relationship of felids and nimravines. We also present an update on East Asian records of barbourofelines. The new skull of Oriensmilus possesses a suite of characters shared with nimravines, such as the lack of an ossified (entotympanic) bullar floor, absence of an intrabullar septum, lack of a ventral promontorial process of the petrosal, presence of a small rostral entotympanic on the dorsal side of the caudal entotympanic, and a distinct caudal entry of the internal carotid artery and nerve that pierces the caudal entotympanic at the junction of the ossified and unossified caudal entotympanics. The absence of an ossified bullar floor in O. liupanensis and its presence in those from the middle Miocene of Sansan, France thus help to bracket the transition of this character, which must have happened in the early part of the middle Miocene. Spatial relationships between bullar construction and the middle ear configuration of the carotid artery in Oriensmilus strongly resemble those in nimravines but are distinctly different from felids and other basal feliforms. Despite the attractive notion that early barbourofelines arose from a Miocene ancestor that also gave rise to felids, the basicranial evidence argues against this view. http://zoobank.org/urn:http://lsid:zoobank.org:pub:2DE98DBC-4D02-4E18-9788-0B0D8587E73F.

Intestinal intraepithelial lymphocytes (IELs) are characterized by an unusual phenotype and developmental pathway, yet their specific ligands and functions remain largely unknown. Here by analysis of QFL T cells, a population of CD8+ T cells critical for monitoring the MHC I antigen processing pathway, we established that unconventional Qa-1b-restricted CD8+ T cells are abundant in intestinal epithelium. We found that QFL T cells showed a Qa-1b-dependent unconventional phenotype in the spleen and small intestine of naïve wild-type mice. The splenic QFL T cells showed innate-like functionality exemplified by rapid response to cytokines or antigens, while the gut population was refractory to stimuli. Microbiota was required for the maintenance, but not the initial gut homing of QFL T cells. Moreover, monocolonization with Pediococcus pentosaceus, which expresses a peptide that cross-activated QFL T cells, was sufficient to maintain QFL T cells in the intestine. Thus, microbiota is critical for shaping the Qa-1b-restricted IEL landscape.

MHC-E restricted CD8 T cells show promise in vaccine settings, but their development and specificity remain poorly understood. Here we focus on a CD8 T cell population reactive to a self-peptide (FL9) bound to mouse MHC-E (Qa-1b) that is presented in response to loss of the MHC I processing enzyme ERAAP, termed QFL T cells. We find that mature QFL thymocytes are predominantly CD8αβ+CD4-, show signs of agonist selection, and give rise to both CD8αα and CD8αβ intraepithelial lymphocytes (IEL), as well as memory phenotype CD8αβ T cells. QFL T cells require the MHC I subunit β-2 microglobulin (β2m), but do not require Qa1b or classical MHC I for positive selection. However, QFL thymocytes do require Qa1b for agonist selection and full functionality. Our data highlight the relaxed requirements for positive selection of an MHC-E restricted T cell population and suggest a CD8αβ+CD4- pathway for development of CD8αα IELs.

Heterochromatin is most often associated with eukaryotic organisms. Yet, bacteria also contain areas with densely protein-occupied chromatin that appear to silence gene expression. One nucleoid-associated silencing factor is the conserved protein Hfq. Although seemingly nonspecific in its DNA binding properties, Hfq is strongly enriched at AT-rich DNA regions, characteristic of prophages and mobile genetic elements. Here, we demonstrate that polyphosphate (polyP), an ancient and highly conserved polyanion, is essential for the site-specific DNA binding properties of Hfq in bacteria. Absence of polyP markedly alters the DNA binding profile of Hfq, causes unsolicited prophage and transposon mobilization, and increases mutagenesis rates and DNA damage–induced cell death. In vitro reconstitution of the system revealed that Hfq and polyP interact with AT-rich DNA sequences and form phase-separated condensates, a process that is mediated by the intrinsically disordered C-terminal extensions of Hfq. We propose that polyP serves as a newly identified driver of heterochromatin formation in bacteria.

The fate of developing T cells is determined by the strength of T cell receptor (TCR) signal they receive in the thymus. This process is finely regulated through the tuning of positive and negative regulators in thymocytes. The Family with sequence similarity 49 member B (Fam49b) protein is a newly discovered negative regulator of TCR signaling that has been shown to suppress Rac-1 activity in vitro in cultured T cell lines. However, the contribution of Fam49b to the thymic development of T cells is unknown. To investigate this important issue, we generated a novel mouse line deficient in Fam49b (Fam49b-KO). We observed that Fam49b-KO double positive (DP) thymocytes underwent excessive negative selection, whereas the positive selection stage was unaffected. Fam49b deficiency impaired the survival of single positive thymocytes and peripheral T cells. This altered development process resulted in significant reductions in CD4 and CD8 single-positive thymocytes as well as peripheral T cells. Interestingly, a large proportion of the TCRγδ+ and CD8αα+TCRαβ+ gut intraepithelial T lymphocytes were absent in Fam49b-KO mice. Our results demonstrate that Fam49b dampens thymocytes TCR signaling in order to escape negative selection during development, uncovering the function of Fam49b as a critical regulator of the selection process to ensure normal thymocyte development and peripheral T cells survival.