Insight into β-Carotene Thermal Degradation in Oils with Multiresponse Modeling

The aim of this study was to gain further insight into β-carotene thermal degradation in oils. Multiresponse modeling was applied to experimental high-performance liquid chromatography–diode array detection (HPLC–DAD) data (trans-, 13-cis-, and 9-cis-β-carotene concentrations) during the heat treatments (120–180 °C) of two β-carotene-enriched oils, i.e., palm olein and copra. The test of different reaction schemes showed that β-carotene isomerization reactions were dominant and reversible. The resulting cis isomers and trans-β-carotene simultaneously underwent oxidation and cleavage reactions at the same rate constant. From the kinetic analysis, it appeared that—contrary to oxidation and cleavage reactions—isomerization rate constants did not follow the Arrhenius law. However, the isomerization equilibrium constant increased with temperature, favoring isomer production, particularly 9-cis-β-carotene. Its production was shown to be concomitant with oxidation and cleavage reactions, indicating that 9-cis-β-carotene could be a good degradation indicator during oil storage or processing.     

Calorimetric study of fluorinated methacrylic and vinyl polymer blends: part 2: correlation between miscibility, chemical structure and χ12 interaction parameter in binary systems

The miscibility of poly(methylmethacrylate) (PMMA) and (trifluoroethyl methacrylic ester-MMA) copolymers (MMA-MATRIFE) with poly(vinylidene fluoride) (PVDF) and VDF copolymers was studied by differential scanning calorimetry (DSC) as a function of the fluorinated copolymer crystallinity and fluoroalkyl methacrylic ester content in the methacrylic copolymer. Miscibility limits were found identical whatever be the blend preparation technique, although solution mixing induced some polymer fractionation, thus giving slightly higher blend glass transition temperature. The miscibility domain widths are reduced when using MMA-MATRIFE copolymers as compared to PMMA-containing blends and miscibility limits are dependent on the MATRIFE content in the methacrylic copolymer. Moreover, PVDF or VDF copolymer melting enthalpy decrease is associated to a partial dissolution of the semi-crystalline polymer in PMMA or MMA-MATRIFE copolymer above the total miscibility limit. The evolution of dynamic moduli as a function of blends composition confirms the miscibility limits determined by DSC. The Flory-Huggins interaction parameters were determined through the melting point depression analysis and compared to correlate the intensity of inter- or intra-molecular interactions between the polymers to the postulated ‘acidity’ of hydrogen atoms in various VDF-containing polymers. The interaction parameter χ₁₂ increases with the fluoroalkyl methacrylic ester content, corresponding to a prevalence of intra-molecular on inter-molecular interactions in these blends. Similarly, PVDF offers higher χ₁₂ values as compared to VDF-TFE or particularly to VDF-TrFE copolymers. These results highlight the importance of the nature of fluorinated polymers and of the inter- or intra-molecular character of dipolar interactions on both, copolymer miscibility and interaction parameter values.     

Thiol-ene “clickable” carbon-chain polymers based on diallyl cyclopropane-1,1-dicarboxylate

A novel type of clickable polymers with a very high local density of allyl side groups was developed. These polymers were obtained by the anionic ring-opening (co)polymerization of diallyl cyclopropane-1,1-dicarboxylate using as an initiating system a protic precursor whose acid–base reaction with the t-BuP₄ phosphazene base generated the initiator in situ. The obtained polymers display geminated allyl groups on every third carbon alongside the macromolecular backbone. Homopolymers as well as block and statistical copolymers have been synthesized, with controlled molecular weights and narrow molecular weight distributions. The coupling of mercaptans with the allyl CC double bonds has been investigated both thermally and photochemically, with the influence of the type of initiation on the efficiency of the polymer modification being discussed in comparison with other “clickable” systems. Further functionalization by several thiols was performed, leading to a range of functional poly(cyclopropane-1,1-dicarboxylate)s.     

Thioether Analogues of Disulfide‐Bridged Cyclic Peptides Targeting Death Receptor 5: Conformational Analysis,Dimerisation and Consequences for Receptor Activation

Cyclic peptides containing redox‐stable thioether bridges might provide a useful alternative to disulfide‐bridged bioactive peptides. We report the effect of replacing the disulfide bridge with a lanthionine linkage in a 16‐mer cyclic peptide that binds to death receptor 5 (DR5, TRAIL‐R2). Upon covalent oligomerisation, the disulfide‐bridged peptide has previously shown similar behaviour to that of TNF‐related apoptosis inducing ligand (TRAIL), by selectively triggering the DR5 cell death pathway. The structural and biological properties of the DR5‐binding peptide and its desulfurised analogue were compared. Surface plasmon resonance (SPR) data suggest that these peptides bind DR5 with comparable affinities. The same holds true for dimeric versions of these peptides: the thioether is able to induce DR5‐mediated apoptosis of BJAB lymphoma and tumorigenic BJELR cells, albeit to a slightly lower extent compared to its disulfide homologue. NMR analysis revealed subtle variation in the conformations of the two peptides and suggests that the thioether peptide is slightly less folded than its disulfide homologue. These observations could account for the different capability of the two dimers to cluster DR5 receptors on the cell surface and to trigger apoptosis. Nevertheless, our results suggest that the thioether peptide is a potential candidate for evaluation in animal models.     

Enzymatic Evidence for a Revised Congocidine Biosynthetic Pathway

Naturally produced pyrrolamides, such as congocidine, are nonribosomal peptides that bind to the minor groove of DNA. Efforts to delineate the biosynthetic machinery responsible for their assembly have mainly employed genetic methods, and the enzymes responsible for their biosynthesis remain largely uncharacterized. We report the biochemical characterization of four proteins involved in congocidine formation: the adenylation‐thiolation (A–T) di‐domain Cgc18(1–610), its MbtH‐like partner SAMR0548, the AMP‐binding enzyme Cgc3*, and the T domain Cgc19. We assayed the ATP‐dependent activation of various commercially available and chemically synthesized compounds with Cgc18(1–610) and Cgc3*. We report the revised substrate specificities of Cgc18(1–610) and Cgc3*, and loading of 4‐acetamidopyrrole‐2‐carboxylic acid onto Cgc19. Based on these biochemical studies, we suggest a revised congocidine biosynthetic pathway.     

Development of novel 1,2,3,4-tetrahydroisoquinoline derivatives and closely related compounds as potent and selective dopamine D3 receptor ligands

Based on N-alkylated 1,2,3,4-tetrahydroisoquinoline derivatives, which are structurally related to the partial agonist BP 897, a series of novel, selective dopamine D3 receptor antagonists has been synthesised. Derivatisation included changes in the arylamide moiety and the tetrahydroisoquinoline substructure leading to compounds with markedly improved selectivities and affinities in the low nanomolar concentration range. From the 55 structures presented here, (E)-3-(4-iodophenyl)-N-(4-(1,2,3,4-tetrahydroisoquinolin-2-yl)butyl)acrylamide (51) has high affinity (Ki(hD3)=12 nM) and a 123-fold preference for the D3 receptor relative to the D2 receptor subtype. Its pharmacological profile offers the prospect of a novel radioligand as a tool for various dopamine D3-receptor-related in vitro and in vivo investigations.     

8-oxoguanine DNA glycosylases: one lesion, three subfamilies

Amongst the four bases that form DNA, guanine is the most susceptible to oxidation, and its oxidation product, 7,8-dihydro-8-oxoguanine (8-oxoG) is the most prevalent base lesion found in DNA. Fortunately, throughout evolution cells have developed repair mechanisms, such as the 8-oxoguanine DNA glycosylases (OGG), which recognize and excise 8-oxoG from DNA thereby preventing the accumulation of deleterious mutations. OGG are divided into three subfamilies, OGG1, OGG2 and AGOG, which are all involved in the base excision repair (BER) pathway. The published structures of OGG1 and AGOG, as well as the recent availability of OGG2 structures in both apo- and liganded forms, provide an excellent opportunity to compare the structural and functional properties of the three OGG subfamilies. Among the observed differences, the three-dimensional fold varies considerably between OGG1 and OGG2 members, as the latter lack the A-domain involved in 8-oxoG binding. In addition, all three OGG subfamilies bind 8-oxoG in a different manner even though the crucial interaction between the enzyme and the protonated N7 of 8-oxoG is conserved. Finally, the three OGG subfamilies differ with respect to DNA binding properties, helix-hairpin-helix motifs, and specificity for the opposite base.     

The preparation of flat H–Si(111) surfaces in 40% NH4F revisited

The reasons why ideally flat H–Si(111) surface can be prepared by NH₄F etching are investigated from correlation between AFM observations and experimental conditions used for etching. It is shown that pitting may be completely suppressed if a one side polished wafer is immersed in an oxygen free solution. An analytical electrochemical study of the (111) and rough face of the same n-Si wafer is presented to yield insight into observations.     

A Survey of Autoencoder Algorithms to Pave the Diagnosis of Rare Diseases

Rare diseases (RDs) concern a broad range of disorders and can result from various origins. For a long time, the scientific community was unaware of RDs. Impressive progress has already been made for certain RDs; however, due to the lack of sufficient knowledge, many patients are not diagnosed. Nowadays, the advances in high-throughput sequencing technologies such as whole genome sequencing, single-cell and others, have boosted the understanding of RDs. To extract biological meaning using the data generated by these methods, different analysis techniques have been proposed, including machine learning algorithms. These methods have recently proven to be valuable in the medical field. Among such approaches, unsupervised learning methods via neural networks including autoencoders (AEs) or variational autoencoders (VAEs) have shown promising performances with applications on various type of data and in different contexts, from cancer to healthy patient tissues. In this review, we discuss how AEs and VAEs have been used in biomedical settings. Specifically, we discuss their current applications and the improvements achieved in diagnostic and survival of patients. We focus on the applications in the field of RDs, and we discuss how the employment of AEs and VAEs would enhance RD understanding and diagnosis.