Pharmacogenetics Biomarkers and Their Specific Role in Neoadjuvant Chemoradiotherapy Treatments: An Exploratory Study on Rectal Cancer Patients

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses.     

Capillary electrophoretic profiling of tryptic digests of water soluble proteins from Bacillus thuringiensis-transgenic and non-transgenic maize species

Capillary zone electrophoresis (CZE) has been applied to separation and characterisation of enzymatic (tryptic) hydrolysates of water-soluble proteins from Bacillus thuringiensis (Bt)-transgenic (Aristis-Bt) and two native non-transgenic (Aristis and Coventry) maize varieties. Water-soluble proteins were extracted from the flour of these maize species and digested by bovine pancreatic trypsin immobilised on agarose gel in 100 mM ammonium hydrocarbonate buffer, pH 7.9. The yielded tryptic digests of proteins were analysed by CZE in four acidic background electrolytes (BGEs) (100 mM H₃PO₄, 50 mM Tris, pH 2.25; 500 mM acetic acid, pH 2.54; 200 mM formic acid, 200 mM acetic acid, pH 2.05; and 200 mM iminodiacetic acid, pH 2.26) using a lab-made CZE apparatus equipped with bare fused silica capillary and UV-absorption detector operating at 206 nm. Among the tested BGEs, the best resolution of the tryptic peptides of extracted proteins of the above three maize species was obtained in isoelectric BGE, 200 mM iminodiacetic acid, pH 2.26. Selected resolved tryptic peptides of proteins were characterised by effective electrophoretic mobilities and corrected (migration times normalised) peak areas. Some significant relative qualitative and quantitative differences in CZE-UV profiling of tryptic protein digests were found, which can be potentially used to differentiate transgenic Aristis Bt and non-transgenic Aristis varieties or two native non-transgenic varieties, Aristis and Coventry.     

Thermally induced microstructure and morphology transformations in molybdenum disulfide–octadecyltrimethylammonim layered nanocomposite

Microstructure of layered nanocomposite compound consisting of molybdenum disulfide single layers and the layers of octadecyltrimethylammonium molecules as well as the structure of destruction products of this hybrid compound were studied by high resolution transmission electron microscopy (HRTEM) and powder X-ray diffraction (XRD) techniques. Changes in composition, ordering and morphology of the host and guest layers of the compound occurring due to release of organic guest from the interlayer space of MoS₂ on heating or on action of electronic beam have been revealed. Removal of the guest was found to initiate formation in the initial layered structure of the packets consisting of a few MoS₂ layers which come close together within the distances of ca. 1–1.5 nm and 0.6–0.7 nm after heating at 250 °C and 400 °C, respectively. Leaving the guest also causes deformations of MoS₂ layers resulting in their non-flat geometry. At 400 °C, strong bending of a part of the sulfide layers with the radius as small as 3–4 nm was observed.     

Changes in the free amino acids and the biogenic amine contents during lactic acid fermentation of different lupin species

The aim of the work was to evaluate the profile of free amino acids (FAA) as the possible precursors of biogenic amines (BAs) in different varieties and hybrid lines of Lupinus luteus and Lupinus angustifolius and its changes during fermentation. Lupins have high amounts of FAA, and therefore, significant contents of BAs by the action of bacterial amino acid decarboxylases can be formed. In view of this, the effect of three Pediococcus pentosaceus strains KTU05‐8, KTU05‐9 and KTU05‐10 on BA formation during lupin fermentation was studied. The formation of BAs was monitored during 48‐h fermentation at solid‐state conditions and compared with that in samples after submerged fermentation and in the control nonfermented samples. The lupin variety, fermentation conditions and the Pediococcus strain were found to have the significant effect on the FAA profile and BA contents in fermented lupin; the interaction between analysed factors was F(5.989) = 1755.321 (P < 0.0001) and F(5.660) = 130.736 (P < 0.0001), respectively. A weak correlation was found between amino acid His and histamine (r = 0.3709; P = 0.0005) and between Phe and phenylethylamine (r = 0.3914, P = 0.0002) in lupin samples, but the significant correlations between amino acid Tyr and tyramine and between Lys and cadaverine were not found. By optimising the fermentation technology, it is possible to increase the nutritional value and functionality of lupin.     

Fluorescent Amines as a New Tool for Study of Siliceous Sponges

Siliceous sponges (Hexactinellida and Demospongiae classes) are aquatic invertebrates which are important both for marine and freshwater ecology and also as the source of biologically active compounds. The sponge skeleton consists of spicules - needle-like or branched composite structures based on silicon dioxide. Mechanisms of silicon assimilation and synthesis of high-ordered glass-like structures at ambient temperatures by sponges are intriguing for biologists, chemists and nanotechnologists. Fluorescent amines are in-vivo dyes that stain growing siliceous frustules of diatom algae so the use of these agents for the sponge study was attempted. We found that cultivation of the Lubomirskia baicalensis (Pallas, 1773) sponge in the presence of fluorescent tracers of biosilica - N¹,N³,N³-trimethyl-N¹-(7-nitro-2,1,3- benzoxadiazol-4-yl)propane-1,3-diamine and N¹,N³-dime thyl-N¹-[3-(dimethylamino)propyl]-N³-(7-nitro-2,1,3-benz oxadiazo-4yl)propane-1,3-diamine results in the staining of growing siliceous spicules. This finding shows that amine dyes accompany silicon from the environment to sponges spicules which opens a new way to study of silicon assimilation by sponges. Fluorescent staining of the growing spicules following with the confocal microscopy can be a powerful tool for morphological studies, revealing information about the dynamics of spiculogenesis and for bio-fabrication of new fluorescent materials.     

Onset of virus systemic infection in plants is determined by speed of cell-to-cell movement and number of primary infection foci

The cornerstone of today''s plant virology consists of deciphering the molecular and mechanistic basis of host–pathogen interactions. Among these interactions, the onset of systemic infection is a fundamental variable in studying both within- and between-host infection dynamics, with implications in epidemiology. Here, we developed a mechanistic model using probabilistic and spatio-temporal concepts to explain dynamic signatures of virus systemic infection. The model dealt with the inherent characteristic of plant viruses to use two different and sequential stages for their within-host propagation: cell-to-cell movement from the initial infected cell and systemic spread by reaching the vascular system. We identified the speed of cell-to-cell movement and the number of primary infection foci in the inoculated leaf as the key factors governing this dynamic process. Our results allowed us to quantitatively understand the timing of the onset of systemic infection, describing this global process as a consequence of local spread of viral populations. Finally, we considered the significance of our predictions for the evolution of plant RNA viruses.     

Trifluoromethylation of [60]- and [70]Fullerene in the Ionization Chamber of a Mass Spectrometer

Abstract

Both [60]- and [70]fullerene react with either the Scherer radical (perfluorodiisopropylethylmethyl, C₉F₁₉), a mixture of branched perfluorononenes (C₉F₁₈, the product of hexafluoropropene trimerization), or β-fluorosulphatotetrafluoroethyldiheptafluoroisopropylmethyl radical (C₉F₁₈OSO₂F) in the ionization chamber of a mass spectrometer to give the positive parent ions of trifluoromethylation products, the reaction being accompanied by hydrogen addition. The reaction occurs at least partly on the walls of the ionization chamber, by a radical mechanism employing CF₃ radicals formed from the radical reactants both thermally and under electron impact; only the latter route occurs with the perfluorononenes.     

Nano-to-macroporous TiO2 (anatase) by cold sintering process

Cold Sintering Process (CSP) was applied on commercial nanopowders to produce nanostructured TiO₂ anatase with nano-to-macro porosity. Nanoporous TiO₂ based materials were obtained by applying CSP at 150 °C and pressures up to 500 MPa on three TiO₂ nanopowders with different specific surface area (s.s.a. = 50, 90 and 370 m²/g), using water as transient aqueous environment. Although TiO₂ is insoluble in water, a density of 68% and s.s.a. = 117 m²/g were achieved from the powder with the highest specific surface area. A post annealing process at 500 °C increased the density up to 73% with a s.s.a. = 59 m²/g, and the crystallites dimensions passed from 110 Å in the powder to 130 Å in CSP material and 172 Å after post annealing. Finally, macroporosity was produced by using thermoplastic polymer beads as sacrificial templates within TiO₂ nanopowder during CSP, followed by a debonding at 500 °C.