Comparative genomics of <em>Fusarium oxysporum</em> f. sp. <em>melonis</em> reveals the secreted protein recognized by the <em>Fom-2</em> resistance gene in melon

Development of resistant crops is the most effective way to control plant diseases to safeguard food and feed production. Disease resistance is commonly based on resistance genes, which generally mediate the recognition of small proteins secreted by invading pathogens. These proteins secreted by pathogens are called 'avirulence' proteins. Their identification is important for being able to assess the usefulness and durability of resistance genes in agricultural settings. We have used genome sequencing of a set of strains of the melon wilt fungus Fusarium oxysporum f. sp. melonis (Fom), bioinformatics-based genome comparison and genetic transformation of the fungus to identify AVRFOM2, the gene that encodes the avirulence protein recognized by the melon Fom-2 gene. Both an unbiased and a candidate gene approach identified a single candidate for the AVRFOM2 gene. Genetic complementation of AVRFOM2 in three different race 2 isolates resulted in resistance of Fom-2-harbouring melon cultivars. AvrFom2 is a small, secreted protein with two cysteine residues and weak similarity to secreted proteins of other fungi. The identification of AVRFOM2 will not only be helpful to select melon cultivars to avoid melon Fusarium wilt, but also to monitor how quickly a Fom population can adapt to deployment of Fom-2-containing cultivars in the field

Protein-like dynamical transition of hydrated polymer chains

Combining elastic incoherent neutron scattering experiments at different resolutions and molecular dynamics simulations, we report the observation of a protein-like dynamical transition in Poly(N-isopropylacrylamide) chains. We identify the onset of the transition at a temperature Td of about 225~K. Thanks to a novel global fit procedure, we find quantitative agreement between measured and calculated polymer mean-squared displacements at all temperatures and time resolutions. Our results confirm the generality of the dynamical transition in macromolecular systems in aqueous environments, independently of the internal polymer topology

The oncofetal RNA-binding protein IGF2BP1 is a druggable, post-transcriptional super-enhancer of E2F-driven gene expression in cancer

The IGF2 mRNA-binding protein 1 (IGF2BP1) is a non-catalytic post-transcriptional enhancer of tumor growth upregulated and associated with adverse prognosis in solid cancers. However, conserved effector pathway(s) and the feasibility of targeting IGF2BP1 in cancer remained elusive. We reveal that IGF2BP1 is a post-transcriptional enhancer of the E2F-driven hallmark in solid cancers. IGF2BP1 promotes G1/S cell cycle transition by stabilizing mRNAs encoding positive regulators of this checkpoint like E2F1. This IGF2BP1-driven shortening of the G1 cell cycle phase relies on 3′UTR-, miRNA- and m6A-dependent regulation and suggests enhancement of cell cycle progression by m6A-modifications across cancers. In addition to E2F transcription factors, IGF2BP1 also stabilizes E2F-driven transcripts directly indicating post-transcriptional 'super'-enhancer role of the protein in E2F-driven gene expression in cancer. The small molecule BTYNB disrupts this enhancer function by impairing IGF2BP1-RNA association. Consistently, BTYNB interferes with E2F-driven gene expression and tumor growth in experimental mouse tumor models

Limits on Dark Matter Effective Field Theory Parameters with CRESST-II

CRESST is a direct dark matter search experiment, aiming for an observation of nuclear recoils induced by the interaction of dark matter particles with cryogenic scintillating calcium tungstate crystals. Instead of confining ourselves to standard spin-independent and spin-dependent searches, we re-analyze data from CRESST-II using a more general effective field theory (EFT) framework. On many of the EFT coupling constants, improved exclusion limits in the low-mass region (< 3-4 GeV) are presented.Comment: 7 pages, 9 figure

First results from the CRESST-III low-mass dark matter program

The CRESST experiment is a direct dark matter search which aims to measure interactions of potential dark matter particles in an earth-bound detector. With the current stage, CRESST-III, we focus on a low energy threshold for increased sensitivity towards light dark matter particles. In this manuscript we describe the analysis of one detector operated in the first run of CRESST-III (05/2016-02/2018) achieving a nuclear recoil threshold of 30.1eV. This result was obtained with a 23.6g CaWO$_4$ crystal operated as a cryogenic scintillating calorimeter in the CRESST setup at the Laboratori Nazionali del Gran Sasso (LNGS). Both the primary phonon/heat signal and the simultaneously emitted scintillation light, which is absorbed in a separate silicon-on-sapphire light absorber, are measured with highly sensitive transition edge sensors operated at ~15mK. The unique combination of these sensors with the light element oxygen present in our target yields sensitivity to dark matter particle masses as low as 160MeV/c$^2$.Comment: 9 pages, 9 figure

Targeting bone metastases starting from the preneoplastic niche: home sweet home

The metastatic process is a multistep coordinated event with a high degree of efficiency. Specific subpopulations of cancer stem cells, with tumor-initiating and migratory capacity, can selectively migrate towards sites that are able to promote survival and/or proliferation of metastatic tumor cells through a microenvironment modification. Cross-talk between the bone microenvironment and cancer cells can facilitate bone tropism of cancer cells. Fully understanding this complexity represents a major challenge in anti-cancer research and a mandatory step towards the development of new drugs potentially able not only to reduce the consequences of bone lesions but also to target the metastatic process in visceral sites