Heterogeneity of the bone marrow niche in patients with myeloproliferative neoplasms: ActivinA secretion by mesenchymal stromal cells correlates with the degree of marrow fibrosis

Mesenchymal stromal cells (MSCs) represent an essential component of the bone marrow (BM) niche and display disease-specific alterations in several myeloid malignancies. The aim of this work was to study possible MSC abnormalities in Philadelphia-negative myeloproliferative neoplasms (MPNs) in relationship to the degree of BM fibrosis. MSCs were isolated from BM of 6 healthy donors (HD) and of 23 MPN patients, classified in 3 groups according to the diagnosis and the grade of BM fibrosis: polycythemia vera and essential thrombocythemia (PV/ET), low fibrosis myelofibrosis (LF-MF), and high fibrosis MF (HF-MF). MSC cultures were established from 21 of 23 MPN patients. MPN-derived MSCs did not exhibit any functional impairment in their adipogenic/osteogenic/chondrogenic differentiation potential and displayed a phenotype similar to HD-derived MSCs but with a decreased expression of CD146. All MPN-MSC lines were negative for the patient-specific hematopoietic clone mutations (JAK2, MPL, CALR). MSCs derived from HF-MF patients displayed a reduced clonogenic potential and a lower growth kinetic compared to MSCs from HD, LF-MF, and PV/ET patients. mRNA levels of hematopoiesis regulatory molecules were unaffected in MSCs from HF-MF compared to HD. Finally, in vitro ActivinA secretion by MSCs was increased in HF-MF compared to LF-MF patients, in association with a lower hemoglobin value. Increased ActivinA immunolabeling on stromal cells and erythroid precursors was also observed in HF-MF BM biopsies. In conclusion, higher grade of BM fibrosis is associated with functional impairment of MSCs and the increased secretion of ActivinA may represent a suitable target for anemia treatment in MF patients

REDUCTIVE DEHALOGENATION OF ALPHA-HALOKETONES PROMOTED BY HYDROIODIC ACID AND WITHOUT SOLVENT

Several alpha-haloketones have been transformed into the corresponding ketones by reaction with aqueous 57% HI, without solvent. The products are obtained in nearly quantitative yields and with high purity (>99%) even in the case of sterically hindered starting materials

FINKELSTEIN REACTION WITH AQUEOUS HYDROGEN HALIDES EFFICIENTLY CATALYZED BY LIPOPHILIC QUARTERNARY ONIUM SALTS

The rate of halogen metathesis between halogenoalkanes RX 1-4 (X = F, Cl, Br, I) and aqueous concentrated hydrogen halides HY (Y = Cl, Br, I) is strongly accelerated under phase-transfer catalysis conditions, without solvent. The amount and nature of the nucleophilic species in the organic phase were determined

Gender specific data in patients with acute appendicitis: a single center perspective

The influence of sex, socioeconomic status and other factors on outcomes from acute illness has been found recently with an increasing interest; acute appendicitis is the most frequent urgency in pediatric age. The aim of this study is to show any gender differences

1H- and 13C-NMR spectra of thiocolchicine and derivatives: A complete analysis

Complete and unambiguous assignments of the 1H- and 13C-nmr spectra of thiocolchicine [1], 3-demethylthiocolchicine [2], and the thiocolchicosides [3] and [4] were made through extensive nmr studies, inclusive of homonuclear COSY and COSYLR, BIRDREV, APT, HETCOR, nOe difference, INEPT, and JMODXH experiments

Isothiazoles. Part IV. Cycloaddition reactions of diaryl-oxazolones and munchnones to 3-diethylamino-4-(4-methoxyphenyl)-isothiazole 1,1-dioxide: A new synthesis of triarylpyrroles

3-Diethylamino-4-(4-methoxyphenyl)-isothiazole 1,1-dioxide (3) readily reacts with oxazolones 2 and munchnones 7 affording with satisfactory yield 3-diethylamino-4,6-diaryl-3a,4-dihydro-3a-(4-methoxyphenyl)-6aH-pyrrol o[3,4-d]isothiazole 1,1-dioxides 4 and 3-diethylamino-4,6-diaryl-5-alkyl-3a-(4-methoxyphenyl)-pyrrolo[3,4-d]i sothiazole 1,1-dioxides 8, respectively. The behaviour of the cycloadducts towards elevated temperatures and/or basic conditions was investigated. Under these conditions the primary products lost SO2 and diethylcyanamide affording 1-alkyl-2,3,5-triarylpyrroles 9 and 1H-2,3,5-triarylpyrroles 10. These latter were found to be better obtained through thermal decompression of N-protected cycloadducts 8 and subsequent deprotecting the final pyrroles

Farmers’ participation in territorial planning: a methodological approach for the case study of Huerta de Valencia

Participation in planning has become progressively important in territory management. As regards Territorial Planning, farmers are among the main stakeholders. In fact multifunctionality of agriculture admits a new role to primary sector. In particular the management of open areas is particularly strategic in peri-urban areas, where competition for resources is highest than in other areas, especially for the land. In this context, the involvement of farmers as privileged stakeholders to land management is even more important. This paper proposes a methodological approach for the evaluation of peri-urban land use plans by farmers, by means of direct surveys on a sample of Spanish farmers. In particular, it has been considered the "Territorial Action Plan of Valencia\u2019s Huerta\u201d (TAPVH)

Susceptibility to entomopathogens and modulation of basal immunity in two insect models at different temperatures.

Abstract In this work, we analysed the efficacy of different commercial bio-insecticides (Steinernema feltiae, Steinernema carpocapsae, Heterorhabditis bacteriophora and Bacillus thuringiensis) by valuating the mortality induced on two insect models, Galleria mellonella (Lepidoptera) and Sarcophaga africa (Diptera) after exposure to different temperatures (10, 20 and 30\u202f\ub0C). Moreover, we investigated the effects of temperature on the basal humoral immunity of the two target insects; particularly, phenoloxidase (PO) and lysozyme activity. Our results show that G. mellonella is susceptible to all bio-insecticides at all the examined temperatures, except when infected at 10\u202f\ub0C with S. carpocapsae and at 30\u202f\ub0C with S. feltiae and B. thuringiensis. S. africa is more susceptible at 30\u202f\ub0C to all bioinsecticides; whereas, when infected at 10 and 20\u202f\ub0C, H. bacteriophora is the most efficient. Temperature modulates PO activity of both G. mellonella and S. africa, otherwise variations in lysozyme activity is observed only in G. mellonella. Except for a possible correlation between the increased lysozyme activity and the delayed Bt efficacy recorded on G. mellonella at 30\u202f\ub0C, a different resistance to bio-insecticides at different temperatures does not seem to be associated to variations of the host basal immunity, probably due to immunoevasive and immunodepressive strategies of these entomopathogens

\u3b1-Pyrones. Part V. Structure effects on the intramolecular cyclization of functionalized 6-pyronylacetamides: synthesis of new 2,5,7-trioxo-pyrano[3,2-c]pyridines

Reaction of arylisocyanates 2 with methyl 2-oxo-2H-pyran-6-acetate 1 and with ylide 4 gave two classes of pyronylacetamides 3 and 5, respectively. Phosphoranes 5 were reduced to the corresponding acetamides 6 with zinc and acetic acid. Compounds 6 were alkylated under solid-liquid PTC conditions using anhydrous potassium carbonate as a base to give the C\u3b1-alkyl derivatives 7 in good yields. Intramolecular cyclization with different bases and solvents of acetamides 3,5-7 to give the new 2,5,7-trioxo-pyrano[3,2-c]pyridines has been studied