Mechanisms of the FMR1 Repeat Instability: How Does the CGG Sequence Expand?

A dynamic mutation in exon 1 of the FMR1 gene causes Fragile X-related Disorders (FXDs), due to the expansion of an unstable CGG repeat sequence. Based on the CGG sequence size, two types of FMR1 alleles are possible: “premutation” (PM, with 56-200 CGGs) and “full mutation” (FM, with >200 triplets). Premutated females are at risk of transmitting a FM allele that, when methylated, epigenetically silences FMR1 and causes Fragile X syndrome (FXS), a very common form of inherited intellectual disability (ID). Expansions events of the CGG sequence are predominant over contractions and are responsible for meiotic and mitotic instability. The CGG repeat usually includes one or more AGG interspersed triplets that influence allele stability and the risk of transmitting FM to children through maternal meiosis. A unique mechanism responsible for repeat instability has not been identified, but several processes are under investigations using cellular and animal models. The formation of unusual secondary DNA structures at the expanded repeats are likely to occur and contribute to the CGG expansion. This review will focus on the current knowledge about CGG repeat instability addressing the CGG sequence expands.     

Two data structures for building tetrahedralizations

A polyhedral decomposition can be unambiguously described as the collection of four primitive elements (i.e., polyhedra, facets, edges, and vertices) plus their mutual adjacency relations. We consider here the problem of representing a specific kind of polyhedral decomposition, i.e., a tetrahedralization. We describe two different representations for a tetrahedralization. The first one can only model polyhedral decompositions with tetrahedral cells, while the second one is suitable for describing any partition of a volume into polyhedral cells with triangular facets. We present two sets of primitive Euler operators, which build and manipulate such representations while maintaining their topological integrity. The use of such operators is demonstrated in connection with two algorithms for building a Delaunay tetrahedralization, which show the different hedralization, which show the different uses of the two representations.     

Hypercholesterolemia in Cancer and in Anorexia Nervosa: A Hypothesis for a Crosstalk

The relationship between cholesterol and cancer has been widely demonstrated. Clinical studies have shown changes in blood cholesterol levels in cancer patients. In parallel, basic research studies have shown that cholesterol is involved in the mechanisms of onset and progression of the disease. On the other hand, anorexic patients have high cholesterol levels and a high susceptibility to cancer. In this review, we first present a brief background on the relations among nutrition, eating disorders and cancer. Using several notable examples, we then illustrate the changes in cholesterol in cancer and in anorexia nervosa, providing evidence for their important relationship. Finally, we show a new possible link between cholesterol disorder in cancer and in anorexia nervosa.     

Limited Accuracy of Pan-Trk Immunohistochemistry Screening for NTRK Rearrangements in Follicular-Derived Thyroid Carcinoma

Patients with advanced thyroid cancer harboring NTRK rearrangements can be treated with highly effective selective inhibitors. Immunohistochemistry (IHC) analysis, to detect Trk protein expression, represents an appealing screening strategy for NTRK rearrangements, but its efficacy has been poorly explored in thyroid cancer. The aim of this study is to investigate the diagnostic utility of Trk IHC in the identification of NTRK rearrangements. A series of 26 follicular-derived thyroid tumors, positive for NTRK rearrangements, and 28 NTRK fusion-negative controls were retrospectively analyzed by IHC using the pan-Trk monoclonal antibody (clone {"type":"entrez-protein","attrs":{"text":"EPR17341","term_id":"523383444","term_text":"EPR17341"}}EPR17341) on the Ventana system. Area under the curve (AUC), sensitivity and specificity were calculated by ROC analysis. Trk expression was detected in 25 samples, including 22 out of the 26 NTRK-rearranged (84.6%) and three out of 28 NTRK-negative samples (10.7%). Four out of twenty-six NTRK-rearranged thyroid tumors were negative for Trk expression (15.4%), all carrying the ETV6/NTRK3 fusion. The AUC, sensitivity and specificity were 0.87, 0.85 and 0.89, respectively. A screening based on IHC analysis showed limited sensitivity and specificity in the identification of NTRK-rearranged tumors. Since falsely negative results could preclude the administration of effective targeted drugs, alternative detection strategies should be considered for thyroid cancer.     

Relevance of AIF/CypA Lethal Pathway in SH-SY5Y Cells Treated with Staurosporine

The AIF/CypA complex exerts a lethal activity in several rodent models of acute brain injury. Upon formation, it translocates into the nucleus of cells receiving apoptotic stimuli, inducing chromatin condensation, DNA fragmentation, and cell death by a caspase-independent mechanism. Inhibition of this complex in a model of glutamate-induced cell death in HT-22 neuronal cells by an AIF peptide (AIF(370-394)) mimicking the binding site on CypA, restores cell survival and prevents brain injury in neonatal mice undergoing hypoxia-ischemia without apparent toxicity. Here, we explore the effects of the peptide on SH-SY5Y neuroblastoma cells stimulated with staurosporine (STS), a cellular model widely used to study Parkinson’s disease (PD). This will pave the way to understanding the role of the complex and the potential therapeutic efficacy of inhibitors in PD. We find that AIF(370-394) confers resistance to STS-induced apoptosis in SH-SY5Y cells similar to that observed with CypA silencing and that the peptide works on the AIF/CypA translocation pathway and not on caspases activation. These findings suggest that the AIF/CypA complex is a promising target for developing novel therapeutic strategies against PD.     

Effect of Formulation on Physicochemical Properties and Water Status of Nutritionally Enriched Fresh Pasta

A standard fresh pasta formulation (STD, the control sample) was modified by introducing soy and carrot ingredients both in dry and in liquid forms (soy and carrot flour and soy milk and carrot juice) to obtain eight nutritionally enriched fresh pasta samples with different formulations. The effect of formulation on selected physicochemical properties and water status of fresh pasta were studied. Colour, texture (force at rupture and extensibility), and cooking loss were found significantly affected by the formulation. Soy and carrot decreased the force at rupture and extensibility of fresh pasta and increased the solids loss during cooking. Improper gluten network development due to either a steric hindrance of soy and carrot solids or improper water availability for gluten hydration due to different water–solid interaction developed were hypothesized. Soy and carrot ingredients significantly altered the water dynamics in the pasta matrix at different space-time levels (macroscopic, moisture content and water activity; macromolecular, frozen water content; molecular, proton nuclear magnetic resonance relaxometry) of fresh pasta in a manner dependent upon the physical state of the added ingredient. Soy flour increased both the frozen water content and the overall proton mobility (¹H FID, ¹H T ₁ and T ₂) of fresh pasta while these parameters did not markedly differed from STD when soy milk was used. The presence of both carrot flour and carrot juice decreased significantly the frozen water content of fresh pasta but, at a molecular level, carrot flour altered the proton molecular mobility, while carrot juice did not.     

Syngas from sugarcane pyrolysis: An experimental study for fuel cell applications

The use of biomass for the production of electrical energy is a promising technological solution for those countries where there are problems with the disposal of agricultural waste and/or the production of low-cost energy. The gasification and/or pyrolysis of the biomass produces a gas rich in hydrogen that can be used in a fuel cell system to produce electrical energy with reduced environmental impact and significant energy recovery.In this work, a study of the pyrolysis of Brazilian sugarcane bagasse was carried out. The experimental process consisted of the pyrolysis of the biomass material in a batch pyrolysis reactor. In some runs the biomass was dry, while in others it was pre-treated by the addition of water. It was noted that the water added to the biomass before the pyrolysis process resulted in a decrease in the quantity of steam added to the fuel cell feeding gas, necessary to avoid carbon deposition, and in an increase in cell power, but, at the same time, caused a decrease in the quantity of syngas produced.Then, the composition of the gas obtained from the experimental pyrolysis of the sugarcane was inserted in a simulation tool of a molten carbonate fuel cell system in order to estimate the feasibility of the entire process in terms of operating conditions and electrical performance.The present study indicates that the syngas obtained from the sugarcane biomass (about 40%) can be converted into electricity using a fuel cell system with a high efficiency.     

Co and Ni supported on CeO2 as selective bimetallic catalyst for dry reforming of methane

Co/CeO₂ (Co 7.5 wt.%), Ni/CeO₂ (Ni 7.5 wt.%) and Co–Ni/CeO₂ (Co 3.75 wt.%, Ni 3.75 wt.%) catalysts were prepared by surfactant assisted co-precipitation method. Samples were characterized by X-Ray diffraction, BET surface areas measurements, temperature programmed reduction and tested for the dry reforming of methane CH₄ + CO₂ → 2CO + 2H₂ in the temperature range 600–800 °C with a CH₄:CO₂:Ar 20:20:60 vol.% feed mixture and a total flow rate of 50 cm³ min⁻¹ (GHSW = 30,000 mL g⁻¹ h⁻¹). The bimetallic Co–Ni/CeO₂ catalyst showed higher CH₄ conversion in comparison with monometallic systems in the whole temperature range, being 50% at 600 °C and 97% at 800 °C. H₂/CO selectivity decreased in the following order: Co–Ni/CeO₂ > Ni/CeO₂ > Co/CeO₂. Carbon deposition on spent catalysts was analyzed by thermal analysis (TG-DTA). After 20 h under stream at 750 °C, cobalt-containing catalysts, Co/CeO₂ and Co–Ni/CeO₂, showed a stable operation in presence of a deposited amorphous carbon of 6 wt.%, whereas Ni/CeO₂ showed an 8% decrease of catalytic activity due to a massive presence of amorphous and graphitic carbon (25 wt.%).     

Persistent organic pollutants in farmed European sea bass (Dicentrarchus labrax,Linnaeus, 1758) from Sicily (Italy)

Farmed European sea bass (Dicentrarchus labrax, Linnaeus, 1758) were collected during 2016 from one Sicilian fish farm that uses two different rearing systems – sea cage and concrete tank – for determination of polychlorinated biphenyls (PCB), organochlorine pesticides (OCP) and polycyclic aromatic hydrocarbons (PAH) residues by HRGC-MS/MS. Moreover, commercial feed was analysed. This study aimed to determine whether the different rearing systems affect the concentration of these compounds, and to assess the safety of cultured fish. PCBs represent the pollutants with the highest concentration; in particular, PCB138 and 153 have the highest concentration in almost all samples. Among OCPs, only 4,4′-DDE, 4,4′-DDD and 4,4′-DDT residues have been detected. Concerning PAHs, only fluorene and phenanthrene were detected, in both rearing systems. Although some residues of organic pollutants were found in the analysed samples, they were always below the MRLs, so the results suggest that farmed sea bass are safe for human consumption.