Detection of irradiated beef by nuclear magnetic resonance lipid profiling combined with chemometric techniques

The combination of ¹H NMR lipid profiling with multivariate analysis was applied to differentiate irradiated and non-irradiated beef. Two pattern recognition chemometric procedures, stepwise linear discriminant analysis (sLDA) and artificial neural networks (ANNs), provided a successful discrimination between the groups investigated. sLDA allowed the classification of 100% of the samples into irradiated or non-irradiated beef groups; the same result was obtained by ANNs using the 1 kGy irradiation dose as discriminant value suggested by the network. Furthermore, sLDA allowed the classification of 81.9% of the beef samples according to the irradiation dose (0, 2.5, 4.5 and 8 kGy). ¹H NMR lipid profiling, coupled with multivariate analysis may be considered a suitable and promising screening tool for the rapid detection of irradiated meat in official control of food.     

Aggregation behaviour of a water-soluble ammonium-functionalized polythiophene: Luminescence enhancement induced by bile-acid anions

The water-soluble poly{trimethyl-[7-(3-thienylsulfanyl)heptyl]ammonium iodide-co-thiophene} (PTN⁺Me₃) forms aggregates whose size span a large range of values, depending on solvent, concentration and film formation conditions. Larger aggregates were detected by atomic force microscopy and dynamic light scattering, smaller ones by DOSY NMR, UV–visible and fluorescence. All techniques indicate a reduced aggregation of PTN⁺Me₃ in DMSO relative to water and a marked de-aggregation of PTN⁺Me₃ in water following addition of bile-acid anions such as deoxycholate and ursodeoxycholate. The latter effect shows itself through a very large enhancement of the polymer photoluminescence likely caused by disruption of aggregated non-emissive exciton traps. A tailored combination of electrostatic and hydrophobic interactions between the polymer and the bile-acid anions seems to be necessary to achieve this effect. These observations suggest that this polythiophene might provide a basis for the development of fluorescent sensors suitable for the detection of medium-sized amphiphilic biomolecules.     

A2A Receptor Dysregulation in Dystonia DYT1 Knock-Out Mice

We aimed to investigate A2A receptors in the basal ganglia of a DYT1 mouse model of dystonia. A2A was studied in control Tor1a+/+ and Tor1a+/− knock-out mice. A2A expression was assessed by anti-A2A antibody immunofluorescence and Western blotting. The co-localization of A2A was studied in striatal cholinergic interneurons identified by anti-choline-acetyltransferase (ChAT) antibody. A2A mRNA and cyclic adenosine monophosphate (cAMP) contents were also assessed. In Tor1a+/+, Western blotting detected an A2A 45 kDa band, which was stronger in the striatum and the globus pallidus than in the entopeduncular nucleus. Moreover, in Tor1a+/+, immunofluorescence showed A2A roundish aggregates, 0.3–0.4 μm in diameter, denser in the neuropil of the striatum and the globus pallidus than in the entopeduncular nucleus. In Tor1a+/−, A2A Western blotting expression and immunofluorescence aggregates appeared either increased in the striatum and the globus pallidus, or reduced in the entopeduncular nucleus. Moreover, in Tor1a+/−, A2A aggregates appeared increased in number on ChAT positive interneurons compared to Tor1a+/+. Finally, in Tor1a+/−, an increased content of cAMP signal was detected in the striatum, while significant levels of A2A mRNA were neo-expressed in the globus pallidus. In Tor1a+/−, opposite changes of A2A receptors’ expression in the striatal-pallidal complex and the entopeduncular nucleus suggest that the pathophysiology of dystonia is critically dependent on a composite functional imbalance of the indirect over the direct pathway in basal ganglia.     

Role of miRNA-19a in Cancer Diagnosis and Poor Prognosis

Cancer is a multifactorial disease that affects millions of people every year and is one of the most common causes of death in the world. The high mortality rate is very often linked to late diagnosis; in fact, nowadays there are a lack of efficient and specific markers for the early diagnosis and prognosis of cancer. In recent years, the discovery of new diagnostic markers, including microRNAs (miRNAs), has been an important turning point for cancer research. miRNAs are small, endogenous, non-coding RNAs that regulate gene expression. Compelling evidence has showed that many miRNAs are aberrantly expressed in human carcinomas and can act with either tumor-promoting or tumor-suppressing functions. miR-19a is one of the most investigated miRNAs, whose dysregulated expression is involved in different types of tumors and has been potentially associated with the prognosis of cancer patients. The aim of this review is to investigate the role of miR-19a in cancer, highlighting its involvement in cell proliferation, cell growth, cell death, tissue invasion and migration, as well as in angiogenesis. On these bases, miR-19a could prove to be truly useful as a potential diagnostic, prognostic, and therapeutic marker.     

The Importance of N186 in the Alpha-1-Antitrypsin Shutter Region Is Revealed by the Novel Bologna Deficiency Variant

Alpha-1-antitrypsin (AAT) deficiency causes pulmonary disease due to decreased levels of circulating AAT and consequently unbalanced protease activity in the lungs. Deposition of specific AAT variants, such as the common Z AAT, within hepatocytes may also result in liver disease. These deposits are comprised of ordered polymers of AAT formed by an inter-molecular domain swap. The discovery and characterization of rare variants of AAT and other serpins have historically played a crucial role in the dissection of the structural mechanisms leading to AAT polymer formation. Here, we report a severely deficient shutter region variant, Bologna AAT (N186Y), which was identified in five unrelated subjects with different geographical origins. We characterized the new variant by expression in cellular models in comparison with known polymerogenic AAT variants. Bologna AAT showed secretion deficiency and intracellular accumulation as detergent-insoluble polymers. Extracellular polymers were detected in both the culture media of cells expressing Bologna AAT and in the plasma of a patient homozygous for this variant. Structural modelling revealed that the mutation disrupts the hydrogen bonding network in the AAT shutter region. These data support a crucial coordinating role for asparagine 186 and the importance of this network in promoting formation of the native structure.     

Therapeutic Acellular Scaffolds for Limiting Left Ventricular Remodelling-Current Status and Future Directions

Myocardial infarction (MI) is one of the leading causes of heart-related deaths worldwide. Following MI, the hypoxic microenvironment triggers apoptosis, disrupts the extracellular matrix and forms a non-functional scar that leads towards adverse left ventricular (LV) remodelling. If left untreated this eventually leads to heart failure. Besides extensive advancement in medical therapy, complete functional recovery is never accomplished, as the heart possesses limited regenerative ability. In recent decades, the focus has shifted towards tissue engineering and regenerative strategies that provide an attractive option to improve cardiac regeneration, limit adverse LV remodelling and restore function in an infarcted heart. Acellular scaffolds possess attractive features that have made them a promising therapeutic candidate. Their application in infarcted areas has been shown to improve LV remodelling and enhance functional recovery in post-MI hearts. This review will summarise the updates on acellular scaffolds developed and tested in pre-clinical and clinical scenarios in the past five years with a focus on their ability to overcome damage caused by MI. It will also describe how acellular scaffolds alone or in combination with biomolecules have been employed for MI treatment. A better understanding of acellular scaffolds potentialities may guide the development of customised and optimised therapeutic strategies for MI treatment.     

State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer

Two-thirds of differentiated thyroid cancer (DTC) patients with distant metastases would be classified as radioactive iodine-refractory (RAIR-DTC), evolving into a poor outcome. Recent advances underlying DTC molecular mechanisms have shifted the therapy focus from the standard approach to targeting specific genetic dysregulations. Lenvatinib and sorafenib are first-line, multitargeted tyrosine kinase inhibitors (TKIs) approved to treat advanced, progressive RAIR-DTC. However, other anti-angiogenic drugs, including single targeted TKIs, are currently being evaluated as alternative or salvage therapy after the failure of first-line TKIs. Combinatorial therapy of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signalling cascade inhibitors has become a highly advocated strategy to improve the low efficiency of the single agent treatment. Recent studies pointed out targetable alternative pathways to overcome the resistance to MAPK and PI3K pathways’ inhibitors. Because radioiodine resistance originates in DTC loss of differentiation, redifferentiation therapies are currently being explored for efficacy. The present review will summarize the conventional management of DTC, the first-line and alternative TKIs in RAIR-DTC, and the approaches that seek to overcome the resistance to MAPK and PI3K pathways’ inhibitors. We also aim to emphasize the latest achievements in the research of redifferentiation therapy, immunotherapy, and agents targeting gene rearrangements in advanced DTC.     

Use of neural networks for quick and accurate auto-tuning of PID controller

With reference to a real industrial application of process control, some considerations are discussed concerning the accuracy of methods for auto-tuning of proportional, integral and derivative factor (PID). In particular, a theoretical–experimental approach is described, that allows to evaluate the adequateness of new methods for auto-tuning of PID, able to significantly reduce the time duration for auto-tuning with respect to traditional ones. This result has been achieved by using suitable techniques of experimental data processing, based on neural-networks algorithms, set for this specific application. The effect on described methodology of environmental and operating disturbances is also described.     

Chemical vapor generation atomic spectrometry using amineboranes and cyanotrihydroborate(III) reagents

Amineboranes of the type L-BH3 (L = NH3; tert-BuNH2; Me2NH; Me3N) and sodium cyanotrihydroborate(III) (NaBH3CN) have been tested as derivatization reagents in the generation of volatile hydrides and elemental mercury following aqueous phase reaction with ionic species of Hg(II), As(III), As(V), Sb(V), Sb(III), Bi(III), Se(IV), Se(VI), Te(IV), and Te(VI). Continuous flow generation atomic absorption spectrometry coupled with a flameless quartz tube atomizer (T = 25 degrees C) and a miniature argon-hydrogen diffusion flame atomizer were employed for the detection of mercury vapors and volatile hydrides, respectively. All of the reductants were able to reduce Hg(II) to the elemental state, giving sensitivities comparable to NaBH4 reduction. Under reaction conditions giving maximum sensitivity for hydride generation with NaBH4, only some amineboranes are able to produce volatile hydrides from all the elements. No evidence of hydride formation was observed from the Se(VI) and Te(VI). In general, the reducing power decreased in the order NaBH4 > H3N-BH3 > tert-BuNH2-BH3 > NaBH3CN > or = Me2HN-BH3 > Me3N-BH3. In comparison with THB, amineboranes and NaBH3CN allowed, in general, a better control of interference effects of Fe(III), Ni(II), Co(II), and Cu(II). Application to determination of mercury in certified reference material is reported. The most likely mechanism of reaction of borane complexes in chemical vapor generation is based on the direct action of hydrogen bound to boron.