Blockade of 6-phosphogluconate dehydrogenase generates CD8+ effector T cells with enhanced anti-tumor function

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Neurons Refine the Caenorhabditis elegans Body Plan by Directing Axial Patterning by Wnts

Metazoans display remarkable conservation of gene families, including growth factors, yet somehow these genes are used in different ways to generate tremendous morphological diversity. While variations in the magnitude and spatio-temporal aspects of signaling by a growth factor can generate different body patterns, how these signaling variations are organized and coordinated during development is unclear. Basic body plans are organized by the end of gastrulation and are refined as limbs, organs, and nervous systems co-develop. Despite their proximity to developing tissues, neurons are primarily thought to act after development, on behavior. Here, we show that in Caenorhabditis elegans, the axonal projections of neurons regulate tissue progenitor responses to Wnts so that certain organs develop with the correct morphology at the right axial positions. We find that foreshortening of the posteriorly directed axons of the two canal-associated neurons (CANs) disrupts mid-body vulval morphology, and produces ectopic vulval tissue in the posterior epidermis, in a Wnt-dependent manner. We also provide evidence that suggests that the posterior CAN axons modulate the location and strength of Wnt signaling along the anterior–posterior axis by employing a Ror family Wnt receptor to bind posteriorly derived Wnts, and hence, refine their distributions. Surprisingly, despite high levels of Ror expression in many other cells, these cells cannot substitute for the CAN axons in patterning the epidermis, nor can cells expressing a secreted Wnt inhibitor, SFRP-1. Thus, unmyelinated axon tracts are critical for patterning the C. elegans body. Our findings suggest that the evolution of neurons not only improved metazoans by increasing behavioral complexity, but also by expanding the diversity of developmental patterns generated by growth factors such as Wnts.     

Towards the use of ecological heterogeneity to design reserve networks: a case study from Dadia National Park,Greece

In this paper, we present a novel approach for using ecological heterogeneity in reserve design. We measured five ecological heterogeneity indices (EHI) and we used a database of six biological groups (woody plants, orchids, orthopterans, aquatic and terrestrial herpetofauna and passerine birds) across 30 sites in a Mediterranean reserve (Greece). We found that all the five EHI were significantly related to the overall species richness and to the species richness of woody plants and birds. Two indices, measuring vertical vegetation complexity (1/D) and horizontal heterogeneity of landcover types (SIDI) in terms of Simpson’s index, predicted well overall species richness and had significantly higher values inside the complementary reserve networks designed after five of the six biological groups. We compared five methods of forming reserve networks. The method of ecological heterogeneity (selecting those sites with the greatest 1/D and then SIDI) was less efficient (non-significantly) than the species-based methods (scoring and complementary networks) but significantly more efficient than the random method (randomly selected network). We also found that the method of complementary ecological heterogeneity (selecting those sites where each EHI had its maximum value) was not that efficient, as it did not differ significantly from the random method. These results underline the potential of the ecological heterogeneity method as an alternative tool in reserve design.     

First experience in clinical application of hyperspectral endoscopy for evaluation of colonic polyps

Early detection and resection of adenomatous polyps prevents their progression to colorectal cancer (CRC), significantly improving patient outcomes. Polyps are typically identified and removed during white-light colonoscopy. Unfortunately, the rate of interval cancers that arise between CRC screening events remains high, linked to poor visualization of polyps during screening and incomplete polyp removal. Here, we sought to evaluate the potential of a hyperspectral endoscope (HySE) to enhance polyp discrimination for detection and resection. We designed, built and tested a new compact HySE in a proof-of-concept clinical study. We successfully collected spectra from three tissue types in seven patients undergoing routine colonoscopy screening. The acquired spectral data from normal tissue and polyps, both pre- and post- resection, were subjected to quantitative analysis using spectral angle mapping and machine learning, which discriminated the data by tissue type, meriting further investigation of HySE as a clinical tool.