The Macrophage Inhibitor CNI-1493 Blocks Metastasis in a Mouse Model of Ewing Sarcoma through Inhibition of Extravasation

Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model of metastatic Ewing Sarcoma, CNI-1493 treatment dramatically reduces metastatic tumor burden. Furthermore, metastases in treated animals have a less invasive morphology. We show in vitro that CNI-1493 decreases M2-stimulated Ewing Sarcoma tumor cell invasion and extravasation, offering a functional mechanism through which CNI-1493 attenuates metastasis. These data indicate that CNI-1493 may be a safe and effective adjuvant agent for the prevention and treatment of metastatic Ewing Sarcoma.     

A compatible interaction of Alternaria brassicicola with Arabidopsis thaliana ecotype DiG: evidence for a specific transcriptional signature

Background  

The interaction of Arabidopsis with Alternaria brassicicola provides a model for disease caused by necrotrophs, but a drawback has been the lack of a compatible pathosystem. Infection of most ecotypes, including the widely-studied line Col-0, with this pathogen generally leads to a lesion that does not expand beyond the inoculated area. This study examines an ecotype, Dijon G (DiG), which is considered sensitive to A. brassicicola.     

Habitat preference in the critically endangered yellow‐tailed woolly monkey (Lagothrix flavicauda) at La Esperanza,Peru

Habitat loss is one of the main threats to wildlife. Therefore, knowledge of habitat use and preference is essential for the design of conservation strategies and identification of priority sites for the protection of endangered species. The yellow‐tailed woolly monkey (Lagothrix flavicauda Humboldt, 1812), categorized as Critically Endangered on the IUCN Red List, is endemic to montane forests in northern Peru where its habitat is greatly threatened. We assessed how habitat use and preference in L. flavicauda are linked to forest structure and composition. The study took place near La Esperanza, in the Amazonas region, Peru. Our objective was to identify characteristics of habitat most utilized by L. flavicauda to provide information that will be useful for the selection of priority sites for conservation measures. Using presence records collected from May 2013 to February 2014 for one group of L. flavicauda, we classified the study site into three different use zones: low‐use, medium‐use, and high‐use. We assessed forest structure and composition for all use zones using 0.1 ha Gentry vegetation transects. Results show high levels of variation in plant species composition across the three use zones. Plants used as food resources had considerably greater density, dominance, and ecological importance in high‐use zones. High‐use zones presented similar structure to medium‐ and low‐use zones; thus it remains difficult to assess the influence of forest structure on habitat preference. We recommend focusing conservation efforts on areas with a similar floristic composition to the high‐use zones recorded in this study and suggest utilizing key alimentation species for reforestation efforts.     

Contributo alla conoscenza della Flora dei pascoli erbosi e boschivi di Monterotondo (Roma)

Summary

After having summarly described the ecological conditions of the area of the Roman Province which are studied by the author, he lists the plants collected and adds some critical remarks on the taxonomy. He gives a list of a few taxa, which must be regarded as having been found for the first time in Lazio, or are infrequent in this Province.

The author describes the vegetation of some pastures and woods by means of statistical investigations. Finaly he takes into consideration the reciprocal influence exerted by the various plant-communities.     

Class similarity and viewpoint invariance in the recognition of 3D objects

 In human vision, the processes and the representations involved in identifying specific individuals are frequently assumed to be different from those used for basic level classification, because classification is largely viewpoint-invariant, but identification is not. This assumption was tested in psychophysical experiments, in which objective similarity between stimuli (and, consequently, the level of their distinction) varied in a controlled fashion. Subjects were trained to discriminate between two classes of computer-generated three-dimensional objects, one resembling monkeys and the other, dogs. Both classes were defined by the same set of 56 parameters, which encoded sizes, shapes, and placement of the limbs, ears, snout, etc. Interpolation between parameter vectors of the class prototypes yielded shapes that changed smoothly between monkey and dog. Within-class variation was induced in each trial by randomly perturbing all the parameters. After the subjects reached 90% correct performance on a fixed canonical view of each object, discrimination performance was tested for novel views that differed by up to 60° from the training view. In experiment 1 (in which the distribution of parameters in each class was unimodal) and in experiment 2 (bimodal classes), the stimuli differed only parametrically and consisted of the same geons (parts), yet were recognized virtually independently of viewpoint in the low-similarity condition. In experiment 3, the prototypes differed in their arrangement of geons, yet the subjects’ performance depended significantly on viewpoint in the high-similarity condition. In all three experiments, higher interstimulus similarity was associated with an increase in the mean error rate and, for misorientation of up to 45°, with an increase in the degree of viewpoint dependence. These results suggest that a geon-level difference between stimuli is neither strictly necessary nor always sufficient for viewpoint-invariant performance. Thus, basic and subordinate-level processes in visual recognition may be more closely related than previously thought. Received: 15 November 1993/Accepted in revised form: 14 July 1994     

An in situ study of beta-glucosidase activity in normal and gaucher fibroblasts with fluorogenic probes

Beta-glucosidase activity was evaluated in situ by means of fluorogenic probes in normal human fibroblasts and fibroblasts from homozygous carriers of the Gaucher trait. Probe internalization, targeting to lysosomes and post-cleavage probe retention were the primary concerns. Internalization and targeting were attempted by in situ photosensitized labilization of lysosomal membranes, lysosomotropic detergents and the use of low density lipid (LDL) or the receptor ligand apolipoprotein E (ApoE). Post-cleavage increase of fluorescence with fluoresceinyl (bis) betaglucopyranoside was appreciably above the rather large pre-cleavage emission. In cells incubated overnight with nonylumbelliferylbetaglucoside (UG9) in the presence of bovine serum albumin and in the absence of ApoE, the probe was dealt with as a cytotoxic agent, accumulating in a paranuclear cap, most likely comprising elements of the endoplasmic reticulum (ER) and Golgi apparatus. Targeting of UG9 to lysosomes occurred within 1 to 3 h of preincubation in the presence of ApoE. There was some evidence of specificity, as Gaucher fibroblasts exhibited weaker cleavage of UG9 (by 50 per cent or more) compared to normal fibroblasts, but in the Gaucher cells there was some residual beta-glucosidase activity. Cleavage of UG9 was nearly totally suppressed in Gaucher cells treated with the beta-glucosidase inhibitor, conduritol B epoxide, for 24 h to 7 days. Suppression in the control fibroblasts was evident but to a lesser degree. The in situ method of fluorogenic assay established for beta-glucosidase deficiency, is in principle applicable to enzyme deficiencies in other lysosomal storage diseases, or to evaluate enhanced enzyme activity following gene therapy.