This finding may represent a general mechanism for “M cone” degeneration in multiple forms of cone degeneration due to M-opsin mislocalization and degradation. These results have important implications for the current gene therapy strategy for LCA that emphasizes the need for combinatorial therapies to both improve vision and slow photoreceptor degeneration. Cell migration inducing hyaluronidase 1 (CEMIP), also known as hyaluronan (HA)-binding protein involved in HA depolymerization (HYBID), plays a role in HA degradation. Cell migration inducing hyaluronidase 2 (CEMIP2), also known as transmembrane protein 2 (TMEM2), possessing a sequence similarity with HYBID, is reported as a hyaluronidase in mice. However, the expression of these molecules in osteoarthritic synovium and their involvement in HA degradation in synovial fluid (SF) from patients with knee osteoarthritis remain elusive. This study examined their expression in synovial tissue and the relationship with molecular weight of HA in SF in knee osteoarthritis patients. Quantification of mRNA demonstrated that HYBID expression is significantly (5.4-fold) higher in osteoarthritic synovium than in normal control synovium, whereas TMEM2 expression level is similar between the two groups. By immunohistochemistry, HYBID was localized mainly to CD68-negative and fibroblast-specific protein 1-positive synovial lining cells and sub-lining fibroblasts in osteoarthritic synovium. The mRNA expression levels of HYBID, but not TMEM2, in osteoarthritic synovium positively correlated with distribution of lower-molecular-weight HA with below 1,000 kDa in SF. HA-degrading activity in osteoarthritic synovial fibroblasts was abrogated by siRNA-mediated knockdown of HYBID. Among the 12 factors examined, interleukin-6 (IL-6) significantly up-regulated the HYBID expression and HA-degrading activity in osteoarthritic synovial fibroblasts. These data suggest that HYBID overexpressed by IL-6-stimulated synovial fibroblasts is implicated in HA degradation in osteoarthritic synovium. Cortactin is an actin-binding protein expressed in virtually all cell types. It regulates several cell functions including adhesion and migration. Cortactin overexpression is associated with increased metastasis formation and worse outcome in different types of solid tumors, thus highlighting a critical role of cortactin in cancer progression. Mechanistically, this is due to increased invadopodia formation and matrix metalloproteinase secretion. Cortactin has been until recently considered absent in hematopoietic cells because these cells express the cortactin homolog hematopoietic cell-specific lyn substrate-1. However, many recent reports describe functional expression of cortactin in different hematopoietic cells such as macrophages, dendritic cells, and lymphocytes. Of note, cortactin is strongly overexpressed in leukemic cell lines and primary patient-derived leukemic cells. In B-cell chronic lymphocytic leukemia this is associated with poor prognosis and increased chemotaxis; whereas in B-cell acute lymphoblastic leukemia, high cortactin levels correlate with treatment failure and relapse. Moreover, cortactin has been proposed as a diagnostic marker for non-Hodgkin B-cell lymphomas. This review summarizes current knowledge on cortactin expression in hematopoietic cells and discusses the functional implications for different hematological malignancies. The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology. Spontaneous preterm labor is frequently caused by an inflammatory response in the gestational tissues elicited by either infectious or sterile agents. In sterile preterm labor, the key regulators of inflammation are not identified, but platelet activating factor (PAF) is implicated as a potential rate-limiting effector agent. Since toll-like receptor 4 (TLR4) can amplify PAF signaling, we evaluated whether TLR4 contributes to inflammation and fetal loss in a mouse model of PAF-induced sterile preterm labor, and whether a small molecule TLR4 inhibitor (+)-naltrexone can mitigate adverse PAF-induced effects. Administration of carbamyl-PAF (cPAF) caused preterm labor and fetal loss in wild-type mice but not in TLR4-deficient (Tlr4-/-) mice. Treatment with (+)-naltrexone prevented preterm delivery and alleviated fetal demise in utero elicited after cPAF administered by intraperitoneal or intrauterine routes. Pups born after cPAF and (+)-naltrexone treatment exhibited comparable rates of postnatal survival and growth to carrier-treated controls. (+)-Naltrexone suppressed the cPAF-induced expression of inflammatory cytokine genes, Il1b, Il6, and Il10 in the decidua, Il6, Il12b, and Il10 in the myometrium, and Il1b and Il6 in the placenta. These data demonstrate that TLR4 antagonist (+)-naltrexoneinhibits the inflammatory cascade induced by cPAF, preventing preterm birth and perinatal death. Inhibition of TLR4 signaling warrants further investigation as a candidate strategy for fetal protection and delaying preterm birth elicited by sterile stimuli. Although autophagy is being pursued as a therapeutic target in clinical oncology trials, its effects on metastasis, the principal cause of cancer mortality, remain unclear. compound library inhibitor Here, we utilize mammary cancer models to temporally delete essential autophagy regulators during carcinoma progression. Though genetic ablation of autophagy strongly attenuates primary mammary tumor growth, impaired autophagy promotes spontaneous metastasis and enables the outgrowth of disseminated tumor cells into overt macro-metastases. Transcriptomic analysis reveals that autophagy deficiency elicits a subpopulation of otherwise luminal tumor cells exhibiting basal differentiation traits, which is reversed upon preventing accumulation of the autophagy cargo receptor, Neighbor to BRCA1 (NBR1). Furthermore, pharmacological and genetic induction of autophagy suppresses pro-metastatic differentiation and metastatic outgrowth. Analysis of human breast cancer data reveal that autophagy gene expression inversely correlates with pro-metastatic differentiation signatures and predicts overall and distant metastasis-free survival.