Proangiogenic TIE2+/CD31+ macrophages are the predominant population of tumor-associated macrophages infiltrating metastatic lymph nodes

Tumor-associated macrophages (TAMs) accumulate in various cancers and promote tumor angiogenesis and metastasis, and thus may be ideal targets for the clinical diagnosis of tumor metastasis with high specificity. However, there are few specific markers to distinguish between TAMs and normal or inflammatory macrophages. Here, we show that TAMs localize in green fluorescent protein-labeled tumors of metastatic lymph nodes (MLNs) from B16F1 melanoma cells but not in necrotic tumor regions, suggesting that TAMs may promote the growth of tumor cells and the progression of tumor metastasis. Furthermore, we isolated pure populations of TAMs from MLNs and characterized their gene expression signatures compared to peritoneal macrophages (PMs), and found that TAMs significantly overexpress immunosuppressive cytokines such as IL-4, IL-10, and TGF-β as well as proangiogenic factors such as VEGF, TIE2, and CD31. Notably, immunological analysis revealed that TIE2⁺/CD31⁺ macrophages constitute the predominant population of TAMs that infiltrate MLNs, distinct from tissue or inflammatory macrophages. Importantly, these TIE2⁺/CD31⁺ macrophages also heavily infiltrated MLNs from human breast cancer biopsies but not reactive hyperplastic LNs. Thus, TIE2⁺/CD31⁺ macrophages may be a unique histopathological biomarker for detecting metastasis in clinical diagnosis, and a novel and promising target for TAM-specific cancer therapy.     

Cdc25B phosphatase participates in maintaining metaphase II arrest in mouse oocytes

Cdc25B is an essential regulator for meiotic resumption in mouse oocytes. However, the role of this phosphatase during the later stage of the meiotic cell cycle is not known. In this study, we investigated the role of Cdc25B during metaphase II (MII) arrest in mouse oocytes. Cdc25B was extensively phosphorylated during MII arrest with an increase in the phosphatase activity toward Cdk1. Downregulation of Cdc25B by antibody injection induced the formation of a pronucleus-like structure. Conversely, overexpression of Cdc25B inhibited Ca²⁺-mediated release from MII arrest. Moreover, Cdc25B was immediately dephosphorylated and hence inactivated during MII exit, suggesting that Cdk1 phosphorylation is required to exit from MII arrest. Interestingly, this inactivation occurred prior to cyclin B degradation. Taken together, our data demonstrate that MII arrest in mouse oocytes is tightly regulated not only by the proteolytic degradation of cyclin B but also by dynamic phosphorylation of Cdk1.     

Decreased mitochondrial OGG1 expression is linked to mitochondrial defects and delayed hepatoma cell growth

Many solid tumor cells exhibit mitochondrial respiratory impairment; however, the mechanisms of such impairment in cancer development remain unclear. Here, we demonstrate that SNU human hepatoma cells with declined mitochondrial respiratory activity showed decreased expression of mitochondrial 8-oxoguanine DNA glycosylase/lyase (mtOGG1), a mitochondrial DNA repair enzyme; similar results were obtained with human hepatocellular carcinoma tissues. Among several OGG1-2 variants with a mitochondrial-targeting sequence (OGG1-2a, -2b, -2c, -2d, and -2e), OGG1-2a was the major mitochondrial isoform in all examined hepatoma cells. Interestingly, hepatoma cells with low mtOGG1 levels showed delayed cell growth and increased intracellular reactive oxygen species (ROS) levels. Knockdown of OGG1-2 isoforms in Chang-L cells, which have active mitochondrial respiration with high mtOGG1 levels, significantly decreased cellular respiration and cell growth, and increased intracellular ROS. Overexpression of OGG1-2a in SNU423 cells, which have low mtOGG1 levels, effectively recovered cellular respiration and cell growth activities, and decreased intracellular ROS. Taken together, our results suggest that mtOGG1 plays an important role in maintaining mitochondrial respiration, thereby contributing to cell growth of hepatoma cells.     

The biomechanical effect of the collar of a femoral stem on total hip arthroplasty

To investigate the biomechanical effect of collars, finite element analyses are carried out through two hip joints that are implanted using collared and collarless stems, respectively, and an intact hip joint model. For the analyses, the sacrum, coxal bone, and the cancellous and cortical bones of a femur are modelled using finite elements based on X-ray computed tomographic images taken from a 27-year-old woman. From the results, it is found that a collar with perfect calcar contact prevents stem subsidence and decreases the proximal–lateral gap and the lateral stem tilting. Therefore, it can impart reasonable biomechanical stability for total hip arthroplasty. However, its low load transmission ability and increased stem tilting effect due to the imperfect contact between the collar and the calcar are found to be serious problems that need to be solved. Results of clinical follow-up are presented for supporting the computational results.     

Review of Dinosaur Tail Traces

Since 1858, when Hitchcock first recorded dinosaur tail traces from the Jurassic of Massachusetts, USA, a number of dinosaur tail traces have been reported. Although considered rare, at least 38 records of dinosaur tail traces have previously been reported in the literature. These occurrences are herein reviewed in order to understand their geographic and stratigraphic distribution, types of tail trace makers, and characteristics of dinosaur tail traces. Several terms for dinosaur tail traces have been employed and they are divided into tail impressions (TIs) for resting traces, and tail drag impressions (TDIs) for locomotion traces. Possible criteria for distinguishing, measuring and comparing TIs and TDIs are suggested. In addition, herringbone structures, one of the characteristic features of tail traces associated with ornithopod and theropod tracks, are discussed. Estimated speeds of tail trace makers are shown to be rather low. Finally, the abundance of tail traces associated with bipedal, rather than quadrupedal, dinosaurs is considered a reflection of behavior.     

Hominid Ichnotaxonomy: An Exploration of a Neglected Discipline

Although more than 60 ancient hominid track sites ranging in age from 3.7 million to less than 500 B. P. are recorded from all continents except Antarctica, no ichnotaxonomic names have ever been formally proposed for hominid tracks. There is no prohibition to the naming of fossil footprints of species that created tracks and trackways similar to those of living species. On the contrary, there is precedent for the naming of ichnotaxa corresponding to the dominant extant vertebrates classes: mammals = Mammalipedia and birds = Avipeda. The hominid track site sample includes only about a dozen sites where footprint preservation is good enough to show details of diagnostic foot morphology and typical trackway morphology. We infer that the Acahualinca Footprint Museum site in Nicaragua represents the most important ancient hominid track site that combines accessibility, a large sample of well-preserved trackways and reliable dating. For this reason, we select the Nicaraguan tracks as the type sample for the new ichnotaxon Hominipes modernus ichnogen., and ichnsp. et ichnosp. nov., which we infer to represent fully modern Homo sapiens. Our preliminary investigations of other track sites suggest that the majority also yield H. modernus. However, at many sites preservation is insufficient to make an ichnotaxonomic designation at the species level or to infer that the trackmaker was H. sapiens. Thus, at many sites including the famous Laetoli site, we apply the more general label of Hominipes isp. indet.     

Induction of the Differentiation of HL-60 Promyelocytic Leukemia Cells by l-Ascorbic Acid

The present study was undertaken to examine the effect of l-ascorbic acid (LAA) on the growth of HL-60 promyelocytic leukemia cells, besides induction of apoptosis. LAA (≥10^-4?M) was found to markedly inhibit the proliferation of HL-60 in liquid culture and clonogenicity in semisolid culture. Moreover, LAA-treated HL-60 showed activity to produce chemiluminescence and expressed CD 66b cell surface antigens, indicating that LAA induces the differentiation of HL-60 mainly into granulocytes. The results are supported by morphological changes of LAA-treated HL-60 into segmented neutrophils. Therefore, the inhibitory effect of LAA on the growth of HL-60 cells seems to arise from the induction of differentiation. To assess the potential role of LAA, cells were exposed to oxygen radical scavengers in the absence or presence of LAA. Catalase abolished and superoxide dismutase promoted LAA-induced differentiation of HL-60. Thus, H²O² produced as a result of LAA treatment seems to play a major role in induction of HL-60 differentiation.     

Cellular defense against heat shock-induced oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase

Heat shock may increase oxidative stress due to increased production of reactive oxygen species and/or the promotion of cellular oxidation events. Mitochondrial NADP⁺-dependent isocitrate dehydrogenase (IDPm) produces NADPH, an essential reducing equivalent for the antioxidant system. The protective role of IDPm against heat shock in HEK293 cells, an embryonic kidney cell line, was investigated in control and cells transfected with the cDNA for IDPm, where IDPm activity was 6–7 fold higher than that in the control cells carrying the vector alone. Upon exposure to heat shock, the viability was lower and the protein oxidation, lipid peroxidation and oxidative DNA damage were higher in control cells as compared to HEK293 cells in which IDPm was over-expressed. We also observed the significant difference in the cellular redox status reflected by the endogenous production of reactive oxygen species, NADPH pool and GSH recycling between two cells. The results suggest that IDPm plays an important role as an antioxidant defense enzyme in cellular defense against heat shock through the removal of reactive oxygen species.