The role of miRNA-221 and miRNA-126 in patients with benign metastasizing leiomyoma of the lung: an overview with new interesting scenarios

Molecular Biology Reports - Benign metastasizing leiomyoma (BML) is a rare disease characterized by extrauterine benign leiomyomatosis in patients with a previous or concomitant history of uterine...     

Speciation-rate dependence in species–area relationships

The general tendency for species number (S) to increase with sampled area (A) constitutes one of the most robust empirical laws of ecology, quantified by species–area relationships (SAR). In many ecosystems, SAR curves display a power-law dependence, S∝A^z. The exponent z is always less than one but shows significant variation in different ecosystems. We study the multitype voter model as one of the simplest models able to reproduce SAR similar to those observed in real ecosystems in terms of basic ecological processes such as birth, dispersal and speciation. Within the model, the species–area exponent z depends on the dimensionless speciation rate ν, even though the detailed dependence is still matter of controversy. We present extensive numerical simulations in a broad range of speciation rates from ν=10^-3 down to ν=10^-11, where the model reproduces values of the exponent observed in nature. In particular, we show that the inverse of the species–area exponent linearly depends on the logarithm of ν. Further, we compare the model outcomes with field data collected from previous studies, for which we separate the effect of the speciation rate from that of the different species lifespans. We find a good linear relationship between inverse exponents and logarithm of species lifespans. However, the slope sets bounds on the speciation rates that can hardly be justified on evolutionary basis, suggesting that additional effects should be taken into account to consistently interpret the observed exponents.     

Synthesis of 6-deoxy-6-chloro and 6-deoxy-6-bromo derivatives of scleroglucan as intermediates for conjugation with methotrexate and other carboxylate containing compounds

Polysaccharides are widely used as carriers in the field of drug delivery. We present a methodology to obtain water soluble drug-conjugates based on scleroglucan. Selective C-6 halogenation gives access to C-6 esters; conjugates between methotrexate and scleroglucan are described, potentially useful for antitumour therapy or in rheumatoid arthritis treatment.     

Thymus‐specific deletion of insulin induces autoimmune diabetes

Insulin expression in the thymus has been implicated in regulating the negative selection of autoreactive T cells and in mediating the central immune tolerance towards pancreatic β‐cells. To further explore the function of this ectopic insulin expression, we knocked out the mouse Ins2 gene specifically in the Aire‐expressing medullary thymic epithelial cells (mTECs), without affecting its expression in the β‐cells. When further crossed to the Ins1 knockout background, both male and female pups (designated as ID‐TEC mice for insulin‐deleted mTEC) developed diabetes spontaneously around 3 weeks after birth. β‐cell‐specific autoimmune destruction was observed, as well as islet‐specific T cell infiltration. The presence of insulin‐specific effector T cells was shown using ELISPOT assays and adoptive T cell transfer experiments. Results from thymus transplantation experiments proved further that depletion of Ins2 expression in mTECs was sufficient to break central tolerance and induce anti‐insulin autoimmunity. Our observations may explain the rare cases of type 1 diabetes onset in very young children carrying diabetes‐resistant HLA class II alleles. ID‐TEC mice could serve as a new model for studying this pathology.     

Gene Expression Profiles of APP and BACE1 in Tg SOD1G93A Cortical Cells

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease defined by motor neuron loss. Transgenic mouse model (Tg SOD1G93A) shows pathological features that closely mimic those seen in ALS patients. An hypothetic link between AD and ALS was suggested by finding an higher amount of amyloid precursor protein (APP) in the spinal cord anterior horn neurons, and of Aβ peptides in ALS patients skin. In this work, we have investigated the expression of some genes involved in Alzheimer’s disease, as APP, β- and γ-secretase, in an animal model of ALS, to understand some possible common molecular mechanisms between these two pathologies. For gene expression analysis, we carried out a quantitative RT-PCR in ALS mice and in transgenic mice over-expressing human wild-type SOD1 (Tg hSOD1). We found that APP and BACE1 mRNA levels were increased 1.5-fold in cortical cells of Tg SOD1G93A mice respect to Tg hSOD1, whereas the expression of γ-secretase genes, as PSEN1, PSEN2, Nicastrin, and APH1a, showed no statistical differences between wild-type and ALS mice. Biochemical analysis carried out by immunostaining and western blotting, did not show any significant modulation of the protein expression compared to the genes, suggesting the existence of post-translational mechanisms that modify protein levels.     

Localization patterns of fibroblast growth factor 1 and its receptors FGFR1 and FGFR2 in postnatal mouse retina

Fibroblast growth factors (FGFs) exert basic functions both during embryonic development and in the adult. The expression of FGFs and their receptors has been reported in mammalian retinas, although information on the organization of the FGF system is still incomplete. Here, we report a detailed double-label immunohistochemical investigation of the localization patterns of FGF1 and its receptors FGFR1 and FGFR2 in adult and early postnatal mouse retinas. In adult retinas, FGF1 is localized to ganglion cells, horizontal cells, and photoreceptor inner and outer segments. FGFR1 is found in ganglion cells and Müller cells, whereas FGFR2 is primarily located in ganglion cells, the nuclei of Müller cells, and glycine-containing amacrine cells. During postnatal development, the patterns of FGF1, FGFR1, and FGFR2 immunostaining are similar to those in the adult, although transient FGF1-expressing cells have been detected in the proximal inner nuclear layer before eye opening. These patterns are consistent with a major involvement of FGF1, FGFR1, and FGFR2 in ganglion cell maturation (during development) and survival (in the adult). Moreover, FGF1 may affect amacrine cell development, whereas Müller cells appear to be regulated via both FGFR1 and FGFR2 throughout postnatal life. In immature retinas, large numbers of amacrine cells, including those containing calbindin and glycine, display both FGF1 and FGFR2 immunoreactivities in their nuclei, suggesting an action of FGF1 on FGFR2 leading to the maturation of these amacrine cells during a restricted period of postnatal development. This work was supported by funding from the Italian Ministry of Education.     

8-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones: Dual-acting 5-HT1 receptor antagonists and serotonin reuptake inhibitors—Part II

8-[2-(4-Aryl-1-piperazinyl)ethyl]-2H-1,4-benzoxazin-3(4H)-ones have been identified as highly potent 5-HT_1A/B/D receptor antagonists with and without additional SerT activity and a high degree of selectivity over hERG potassium channels. Modulation of the different target activities gave compounds with a range of profiles suitable for further in vivo characterization.     

Properly substituted 1,4-dioxane nucleus favours the selective M3 muscarinic receptor activation

Novel analogues of cis-N,N,N-trimethyl-(6-methyl-1,4-dioxan-2-yl)methanaminium iodide (2a) were synthesized by inserting methyl groups alternatively or simultaneously in positions 5 and 6 of the 1,4-dioxane nucleus in all combinations. Their biological profile was assessed by receptor binding assays at human muscarinic M₁–M₅ receptors stably expressed in CHO cells and by functional studies performed on classical isolated organ preparations, namely, rabbit electrically stimulated vas deferens, and guinea pig electrically stimulated left atrium, ileum, and lung strips. The results showed that the simultaneous presence of one methyl group in both positions 5 and 6 with a trans stereochemical relationship with each other (diastereomers 4 and 5) or the geminal dimethylation in position 6 (compound 8) favour the selective activation of M₃ receptors. Compounds 4, 5, and 8 might be valuable tools in the characterization of the M₃ receptor, as well as provide useful information for the design and development of novel selective M₃ antagonists.