miRNA Expression Is Increased in Serum from Patients with Semantic Variant Primary Progressive Aphasia

Primary progressive aphasia (PPA) damages the parts of the brain that control speech and language. There are three clinical PPA variants: nonfluent/agrammatic (nfvPPA), logopenic (lvPPA) and semantic (svPPA). The pathophysiology underlying PPA variants is not fully understood, including the role of micro (mi)RNAs which were previously shown to play a role in several neurodegenerative diseases. Using a two-step analysis (array and validation through real-time PCR), we investigated the miRNA expression pattern in serum from 54 PPA patients and 18 controls. In the svPPA cohort, we observed a generalized upregulation of miRNAs with miR-106b-5p and miR-133a-3p reaching statistical significance (miR-106b-5p: 2.69 ± 0.89 mean ± SD vs. 1.18 ± 0.28, p < 0.0001; miR-133a-3p: 2.09 ± 0.10 vs. 0.74 ± 0.11 mean ± SD, p = 0.0002). Conversely, in lvPPA, the majority of miRNAs were downregulated. GO enrichment and KEGG pathway analyses revealed that target genes of both miRNAs are involved in pathways potentially relevant for the pathogenesis of neurodegenerative diseases. This is the first study that investigates the expression profile of circulating miRNAs in PPA variant patients. We identified a specific miRNA expression profile in svPPA that could differentiate this pathological condition from other PPA variants. Nevertheless, these preliminary results need to be confirmed in a larger independent cohort.     

5-Hydroxytryptamine Modulates Maturation and Mitochondria Function of Human Oligodendrocyte Progenitor M03-13 Cells

Inside the adult CNS, oligodendrocyte progenitor cells (OPC_S) are able to proliferate, migrate and differentiate into mature oligodendrocytes (OLs) which are responsible for the production of myelin sheet and energy supply for neurons. Moreover, in demyelinating diseases, OPCs are recruited to the lesion areas where they undergo differentiation and myelin synthesis. Serotonin (5-hydroxytryptamine, 5-HT) is involved in OLs’ development and myelination, but so far the molecular mechanisms involved or the effects of 5-HT on mitochondria function have not yet been well documented. Our data show that 5-HT inhibits migration and proliferation committing cells toward differentiation in an immortalized human oligodendrocyte precursor cell line, M03-13. Migration blockage is mediated by reactive oxygen species (ROS) generation since antioxidants, such as Vit C and Cu-Zn superoxide dismutase, prevent the inhibitory effects of 5-HT on cell migration. 5-HT inhibits OPC migration and proliferation and increases OL phenotypic markers myelin basic protein (MBP) and Olig-2 via protein kinase C (PKC) activation since the inhibitor of PKC, bis-indolyl-maleimide (BIM), counteracts 5-HT effects. NOX inhibitors as well, reverse the effects of 5-HT, indicating that 5-HT influences the maturation process of OPCs by NOX-dependent ROS production. Finally, 5-HT increases mitochondria function and antioxidant activity. The identification of the molecular mechanisms underlying the effects of 5-HT on maturation and energy metabolism of OPCs could pave the way for the development of new treatments for autoimmune demyelinating diseases such as Multiple Sclerosis where oligodendrocytes are the primary target of immune attack.     

A Fluorescent Silver(I) Carbene Complex with Anticancer Properties: Synthesis,Characterization, and Biological Studies

The silver(I) N-heterocyclic carbene (NHC) complex bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) silver chloride ([Ag(EIA)₂]Cl), bearing two anthracenyl fluorescent probes, has been synthesized and characterized. [Ag(EIA)₂]Cl is stable in organic solvents and under physiological conditions, and shows potent cytotoxic effects in vitro toward human SH-SY5Y neuroblastoma cells. The interactions of [Ag(EIA)₂]Cl with a few model biological targets have been studied as well as its ability to be internalized in cells. The in vitro anticancer activity is apparently related to the level of drug internalization. Notably, [Ag(EIA)₂]Cl does not react with a few model proteins, but is capable of binding the C-terminal dodecapeptide of thioredoxin reductase hTrxR(488–499) and to strongly inhibit the activity of this enzyme. Binding occurs through an unconventional process leading to covalent binding of one or two carbene ligands to the C-terminal dodecapeptide with concomitant release of the silver cation. To the best of our knowledge, this mode of interaction is reported here for the first time for Ag(NHC)₂ complexes.     

Dynamic malware detection and phylogeny analysis using process mining

International Journal of Information Security - In the last years, mobile phones have become essential communication and productivity tools used daily to access business services and exchange...     

DataMock: An Agile Approach for Building Data Models from User Interface Mockups

Software and Systems Modeling - In modern software development, much time is devoted and much attention is paid to the activity of data modeling and the translation of data models into databases....     

Factors associated with herd bulk milk composition and technological traits in the Italian dairy industry

The aim of the present study was to investigate sources of variation of milk composition and technological characteristics routinely collected in field conditions in the Italian dairy industry. A total of 40,896 bulk milk records from 620 herds and 10 regions across Italy were analyzed. Composition traits were fat, protein, and casein percentages, urea content, and somatic cell score; and technological characteristics were rennet coagulation time, curd firming time, curd firmness 30 min after rennet addition to milk, and titratable acidity. Data of herd bulk milks were analyzed using a model that included fixed effects of region, herd nested within region, and season of milk analysis. An average good milk quality was reported in the dairy industry (especially concerning fat, protein, and casein percentages), and moderate to high correlations between composition and technological traits were observed. All factors included in the statistical model were significant in explaining the variation of the studied traits except for region effect in the analysis of casein and somatic cell score. Northeast and central-southern Italian regions showed the best performance for composition and technological features, respectively. Traits varied greatly across regions, which could reflect differences in herd management and strategies. Overall, less suitable milk for dairy processing was observed in summer. Results of the present study suggested that a constant monitoring of technological traits in the dairy industry is necessary to improve production quality at herd level and it may be a way to segregate milk according to its processing characteristics.     

Bisphenol A,octylphenols and nonylphenols in fish muscle determined by LC/ESI-MS/MS after affinity chromatography clean up

ABSTRACT

An analytical method is applied to simultaneously determine bisphenol A, 4-octylphenol, 4-tert-octylphenol, 4-nonylphenol and tert-nonylphenol in fish muscle. The method consisted of a cleanup on molecularly imprinted polymers cartridges (MIPs) followed by liquid chromatography coupled to a tandem mass spectrometer. The method is rapid, specific, reliable and very sensitive, allowing for quantification down to 0.5 ng/g for all studied compounds. After in-house validation, the method was employed to monitor the concentration levels of BPA and four target alkylphenols in 44 marine fish, collected from third countries in the frame of official control activities. The results showed that 27 samples (61.4%) were contaminated by at least one target compound. Bisphenol A was determined in 11 samples in the range 0.6–7.1 ng/g, 4-tert-octylphenol in 8 samples (0.5–1.6 ng/g) and tert-nonylphenol in 14 samples (0.8–8.9 ng/g). 4-Octylphenol and 4-nonylphenol were not detected at all.     

Possible Prognostic and Therapeutic Significance of c-Kit Expression,Mast Cell Count and Microvessel Density in Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most frequent renal tumor and its incidence is increasing worldwide. Tumor angiogenesis is known to play a crucial role in the etiopathogenesis of RCC and over the last few years an even deeper knowledge of its contribution in metastatic RCC development has led to the development of numerous molecular targeting agents (such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib). The above agents are principally directed against vascular endothelial growth factor receptor (VEGFR) members and also against c-Kit receptor (c-KitR). The role of c-kitR inhibition on clear cell RCC (ccRCC), the main RCC subtype, is less well established. Whether c-kitR activation through its ligand, stem cell factor (SCF) contributes significantly to the effects of tyrosine kinase inhibitors (TKIs) treatment remains to be established. It is important to underscore that the c-KitR is expressed on mast cells (MCs) and cancer cells. After an examination of the c-KitR/SCF pathway, we review here the principal studies that have evaluated c-Kit expression in RCC. Moreover, we summarize some investigations that have observed the distribution of MCs in primary renal cancer and in adjacent normal tissue with appropriate histological immunohistochemical techniques. We also focus on few studies that have evaluated the correlation between RCC proliferation, MC count and microvessel density (MVD), as hallmarks of tumor angiogenesis. Thus, the aim of this review of the literature is to clarify if c-KitR expression, MC count and MVD could have prognostic significance and the possible predictive therapeutic implications in RCC.     

Precipitation and hardening behaviour of the Fe20Co18W alloy aged at 800 °C

The hardness and the microstructure evolution are studied in the Fe20Co18W (mass %) alloy aged at 800 °C after a solution treatment at 1380 °C. The hardness strongly increases at the onset of the annealing treatment then decreases. The precipitation sequence is characterized using X-ray diffraction and transmission electron microscopy. Several phases are identified during the annealing: nanometric W rich clusters, FeCoW ordered domains, nanometric plate shaped precipitates of Laves phase then micrometric Laves phase precipitates. The specific effect of Co addition on mechanical properties of FeCoW alloys is likely due to the formation of the FeCoW ordered compound at the beginning of aging and to the larger stability domain of the Laves phase in these alloys.