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The molecular basis of advanced systemic mastocytosis (SM) is not fully understood and despite novel therapies the prognosis remains dismal. Exome sequencing of an index-patient with mast cell leukemia (MCL) uncovered biallelic loss-of-function mutations in the SETD2 histone methyltransferase gene. Copy-neutral loss-of-heterozygosity at 3p21.3 (where SETD2 maps) was subsequently found in SM patients and prompted us to undertake an in-depth analysis of SETD2 copy number, mutation status, transcript expression and methylation levels, as well as functional studies in the HMC-1 cell line and in a validation cohort of 57 additional cases with SM, including MCL, aggressive SM and indolent SM. Reduced or no SETD2 protein expression--and consequently, H3K36 trimethylation--was found in all cases and inversely correlated with disease aggressiveness. Proteasome inhibition rescued SETD2 expression and H3K36 trimethylation and resulted in marked accumulation of ubiquitinated SETD2 in SETD2-deficient patients but not in patients with near-normal SETD2 expression. Bortezomib and, to a lesser extent, AZD1775 alone or in combination with midostaurin induced apoptosis and reduced clonogenic growth of HMC-1 cells and of neoplastic mast cells from advanced SM patients. Our findings may have implications for prognostication of SM patients and for the development of improved treatment approaches in advanced SM.

Coppice silviculture has a long tradition in Italy. Societal demands have led to the development of forest management techniques for integrating wood production with other kinds of forest uses and regulations have been issued to limit forest degradation. In Italy, 35% of the national forest cover is currently managed under coppice silvicultural systems that provide 66% of the annual wood production. Fuel-wood demand is increasing and a large amount of fuel-wood is currently imported in Italy. Modern coppice practices differ from those adopted in the past and may have a reduced impact on ecosystem characteristics and processes. Nevertheless, coppice silviculture has a bad reputation mostly on grounds that are beyond economic, technical and ecological rationales. Neither cessation of use nor a generalized conversion from coppice to high forest are likely to respond simultaneously to the many demands deriving from complex and articulated political and economic perspectives operating at global, European, national, regional and forest stand-level scales. Different approaches of modern silviculture to coppice successfully tested in Italy for more than a decade are illustrated. We propose to combine different options at the stand and sub-stand level, including either development without human interference or conversion to high forest, and to apply these approaches within the framework of novel forest management plans and regionally consistent administrative procedures. This bottom-up approach represents a potential solution to the socio-economic and environmental challenges affecting coppicing as a silvicultural system.

Mast cell leukemia (MCL) is a very rare form of systemic mastocytosis (SM) with a short median survival of 6 months. We describe a case of a 65-year-old woman with aleukaemic variant of MCL with a very high serum total tryptase level of 2255 μg/L at diagnosis, which occurred following an episode of hypotensive shock. She fulfilled the diagnostic criteria of SM, with a bone marrow smear infiltration of 50–60% of atypical mast cells (MCs). She tested negative for the KIT D816V mutation, without any sign of organ damage (no B- or C-findings) and only few mediator-related symptoms. She was treated with antihistamine alone and then with imatinib for the appearance of anemia. She maintained stable tryptase level and a very indolent clinical course for twenty-two months; then, she suddenly progressed to acute MCL with a serum tryptase level up to 12960 μg/L. The patient died due to haemorrhagic diathesis twenty-four months after diagnosis. This clinical case maybe represents an example of the chronic form of mast cell leukemia, described as unpredictable disease, in which the serum total tryptase level has confirmed itself as a reliable marker of mast cells burden regardless of the presence of other signs or symptoms.

2-methyl-8-ethylquinoline (MEQUI) was synthesized from ethylene glycol and an excess of 2-ethylaniline, operating in the vapour phase on K10 montmorillonite. Its structure was confirmed by 1H-NMR (200 MHz) spectra recorded in CDCl3 and DMSO. The synthesis of MEQUI is favoured by increasing the reaction temperature and amount of ethylene glycol, operating in a partially reducing atmosphere and feeding small amounts of water inside the organic feed. A possible reaction pathway proposed was confirmed by feeding a 2-ethylaniline/crotonaldehyde mixture.

Nicaltica new genus and new species (N. selvanegra Konstantinov, Chamorro-Lacayo and Savini) from moss habitat in Nicaragua are described and illustrated. Nicaltica is compared to Kiskeya Konstantinov and Chamorro-Lacayo, Monotalla Bechyné, and Normaltica Konstantinov.

Raman spectroscopy has already proved to be a powerful tool for studying the properties of single graphene layers. It is now shown that this technique can also provide information on the interaction between graphene sheets in multilayered graphene structures. In particular, a Raman peak corresponding to the interlayer shear mode, and probably linked to the interlayer coupling, is unveiled. The quest for materials capable of realizing the next generation of electronic and photonic devices continues to fuel research on the electronic, optical and vibrational properties of graphene. Few-layer graphene (FLG) flakes with less than ten layers each show a distinctive band structure. Thus, there is an increasing interest in the physics and applications of FLGs. Raman spectroscopy is one of the most useful and versatile tools to probe graphene samples. Here, we uncover the interlayer shear mode of FLGs, ranging from bilayer graphene (BLG) to bulk graphite, and suggest that the corresponding Raman peak measures the interlayer coupling. This peak scales from ~43 cm −1 in bulk graphite to ~31 cm −1 in BLG. Its low energy makes it sensitive to near-Dirac point quasiparticles. Similar shear modes are expected in all layered materials, providing a direct probe of interlayer interactions.

Invasive aspergillosis is a common opportunistic infection, causing >50% mortality in infected immunocompromised patients. The specific molecular mechanisms of the innate immune system that prevent pathogenesis of invasive aspergillosis in immunocompetent individuals are not fully understood. Here, we used a zebrafish larva- Aspergillus infection model to identify cyclooxygenase (COX) enzyme signaling as one mechanism that promotes host survival. Larvae exposed to the pan-COX inhibitor indomethacin succumb to infection at a significantly higher rate than control larvae. COX signaling is both macrophage- and neutrophil-mediated. However, indomethacin treatment has no effect on phagocyte recruitment. Instead, COX signaling promotes phagocyte-mediated inhibition of germination and invasive hyphal growth. Increased germination and invasive hyphal growth is also observed in infected F0 crispant larvae with mutations in genes encoding for COX enzymes ( ptgs2a/b ). Protective COX-mediated signaling requires the receptor EP2 and exogenous prostaglandin E 2 (PGE 2 ) rescues indomethacin-induced decreased immune control of fungal growth. Collectively, we find that COX signaling activates the PGE 2 -EP2 pathway to increase control A . fumigatus hyphal growth by phagocytes in zebrafish larvae.

Dietary mono-unsaturated fatty acids (MUFAs) are linked to longevity in several species. But the mechanisms by which MUFAs extend lifespan remain unclear. Here we show that an organelle network involving lipid droplets and peroxisomes is critical for MUFA-induced longevity in Caenorhabditis elegans . MUFAs upregulate the number of lipid droplets in fat storage tissues. Increased lipid droplet number is necessary for MUFA-induced longevity and predicts remaining lifespan. Lipidomics datasets reveal that MUFAs also modify the ratio of membrane lipids and ether lipids—a signature associated with decreased lipid oxidation. In agreement with this, MUFAs decrease lipid oxidation in middle-aged individuals. Intriguingly, MUFAs upregulate not only lipid droplet number but also peroxisome number. A targeted screen identifies genes involved in the co-regulation of lipid droplets and peroxisomes, and reveals that induction of both organelles is optimal for longevity. Our study uncovers an organelle network involved in lipid homeostasis and lifespan regulation, opening new avenues for interventions to delay aging. Papsdorf et al. show that mono-unsaturated fatty acids extend lifespan of C. elegans through induction of peroxisomes and lipid droplets in fat tissues and of a lipid signature predictive of decreased lipid oxidation.