Down Regulation of a Gene for Cadherin, but Not Alkaline Phosphatase, Associated with Cry1Ab Resistance in the Sugarcane Borer Diatraea saccharalis

The sugarcane borer, Diatraea saccharalis, is a major target pest of transgenic corn expressing Bacillus thuringiensis (Bt) proteins (i.e., Cry1Ab) in South America and the mid-southern region of the United States. Evolution of insecticide resistance in such target pests is a major threat to the durability of transgenic Bt crops. Understanding the pests' resistance mechanisms will facilitate development of effective strategies for delaying or countering resistance. Alterations in expression of cadherin- and alkaline phosphatase (ALP) have been associated with Bt resistance in several species of pest insects. In this study, neither the activity nor gene regulation of ALP was associated with Cry1Ab resistance in D. saccharalis. Total ALP enzymatic activity was similar between Cry1Ab-susceptible (Cry1Ab-SS) and -resistant (Cry1Ab-RR) strains of D. saccharalis. In addition, expression levels of three ALP genes were also similar between Cry1Ab-SS and -RR, and cDNA sequences did not differ between susceptible and resistant larvae. In contrast, altered expression of a midgut cadherin (DsCAD1) was associated with the Cry1Ab resistance. Whereas cDNA sequences of DsCAD1 were identical between the two strains, the transcript abundance of DsCAD1 was significantly lower in Cry1Ab-RR. To verify the involvement of DsCAD1 in susceptibility to Cry1Ab, RNA interference (RNAi) was employed to knock-down DsCAD1 expression in the susceptible larvae. Down-regulation of DsCAD1 expression by RNAi was functionally correlated with a decrease in Cry1Ab susceptibility. These results suggest that down-regulation of DsCAD1 is associated with resistance to Cry1Ab in D. saccharalis

Memcomputing NP

Memcomputing is a novel non-Turing paradigm of computation that uses interacting memory cells (memprocessors for short) to store and process information on the same physical platform. It was recently proved mathematically that memcomputing machines have the same computational power of non-deterministic Turing machines. Therefore, they can solve NP-complete problems in polynomial time and, using the appropriate architecture, with resources that only grow polynomially with the input size. The reason for this computational power stems from properties inspired by the brain and shared by any universal memcomputing machine, in particular intrinsic parallelism and information overhead, namely the capability of compressing information in the collective state of the memprocessor network. Here, we show an experimental demonstration of an actual memcomputing architecture that solves the NP-complete version of the subset-sum problem in only one step and is composed of a number of memprocessors that scales linearly with the size of the problem. We have fabricated this architecture using standard microelectronic technology so that it can be easily realized in any laboratory setting. Even though the particular machine presented here is eventually limited by noise--and will thus require error-correcting codes to scale to an arbitrary number of memprocessors--it represents the first proof-of-concept of a machine capable of working with the collective state of interacting memory cells, unlike the present-day single-state machines built using the von Neumann architecture.Comment: We have corrected minor typos and improved the presentatio

Defining Standards in Experimental Microsurgical Training: Recommendations of the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM)

LBK

A novel L1CAM isoform with angiogenic activity generated by NOVA2-mediated alternative splicing

The biological players involved in angiogenesis are only partially defined. Here, we report that endothelial cells (ECs) express a novel isoform of the cell-surface adhesion molecule L1CAM, termed L1-ΔTM. The splicing factor NOVA2, which binds directly to L1CAM pre-mRNA, is necessary and sufficient for the skipping of L1CAM transmembrane domain in ECs, leading to the release of soluble L1-ΔTM. The latter exerts high angiogenic function through both autocrine and paracrine activities. Mechanistically, L1-ΔTM-induced angiogenesis requires fibroblast growth factor receptor-1 signaling, implying a crosstalk between the two molecules. NOVA2 and L1-ΔTM are overexpressed in the vasculature of ovarian cancer, where L1-ΔTM levels correlate with tumor vascularization, supporting the involvement of NOVA2-mediated L1-ΔTM production in tumor angiogenesis. Finally, high NOVA2 expression is associated with poor outcome in ovarian cancer patients. Our results point to L1-ΔTM as a novel, EC-derived angiogenic factor which may represent a target for innovative antiangiogenic therapies.This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC, projects IG-17395 to CG, IG-14622 to UC, IG-18683 to ED and IG-18853 to RG, IG-19919 to DG), Worldwide Cancer Research (formerly known as Association for International Cancer Research; AICR 10–0091 to UC), the European Research Council (ERC) under the European Union's Horizon 2020 program (ERC-StG-LS2-637591 to MI) and the Spanish Ministerio de Economía y Competitividad (BFU2017-89201-P to MI). EB, FA and ADM were supported by AIRC - FIRC ITALY postdoctoral fellowships. MG was supported by a fellowship from Fondazione IEO-CCM. Research in FF laboratory is supported by The Giovanni Armenise-Harvard Foundation, and by the Italian Ministry for Education, University and Research (MIUR): Programma Giovani Ricercatori "Rita Levi-Montalcini" and Dipartimenti di Eccellenza Program (2018–2022) - Dept. of Biology and Biotechnology "L. Spallanzani", University of Pavia. AC is supported by a Marie Curie Individual Fellowship from the Horizon 2020 EU Program (Grant agreement n. 745934 – COTETHERS)

Fibroblast Growth Factor Receptor-2 Expression in Thyroid Tumor Progression: Potential Diagnostic Application

Fibroblast growth factor receptor-2 (FGFR-2) plays an important role in tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation, but the role of this receptor has not been yet clarified. Therefore, we decided to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in different histological thyroid variants such as hyperplasia, follicular adenoma and papillary carcinoma. Immunohistochemistry and quantitative Real-Time PCR analyses were performed on samples of hyperplasia, follicular adenoma and papillary carcinoma, compared with normal thyroid tissue. Thyroid hyperplasia did not show statistically significant reduction in FGFR-2 protein and mRNA levels. Interestingly, in both follicular adenoma and papillary carcinoma samples we observed a strongly reduced expression of both FGFR-2 isoforms. We speculate that FGFR-2 down-modulation might be an early event in thyroid carcinogenesis. Furthermore, we suggest the potential use of FGFR-2 as an early marker for thyroid cancer diagnosis