β-cyclodextrin (βCyD) derivatives equipped with aromatic appendages at the secondary face exhibit tailorable self-assembling capabilities. The aromatic modules can participate in inclusion phenomena ...and/or aromatic–aromatic interactions. Supramolecular species can thus form that, at their turn, can engage in further co-assembling with third components in a highly regulated manner; the design of nonviral gene delivery systems is an illustrative example. Endowing such systems with stimuli responsiveness while keeping diastereomeric purity and a low synthetic effort is a highly wanted advancement. Here, we show that an azobenzene moiety can be “clicked” to a single secondary O-2 position of βCyD affording 1,2,3-triazole-linked βCyD-azobenzene derivatives that undergo reversible light-controlled self-organization into dimers where the monomer components face their secondary rims. Their photoswitching and supramolecular properties have been thoroughly characterized by UV–vis absorption, induced circular dichroism, nuclear magnetic resonance, and computational techniques. As model processes, the formation of inclusion complexes between a water-soluble triazolylazobenzene derivative and βCyD as well as the assembly of native βCyD/βCyD-azobenzene derivative heterodimers have been investigated in parallel. The stability of the host–guest supramolecules has been challenged against the competitor guest adamantylamine and the decrease of the medium polarity using methanol–water mixtures. The collective data support that the E-configured βCyD-azobenzene derivatives, in aqueous solution, form dimers stabilized by the interplay of aromatic–aromatic and aromatic-βCyD cavity interactions after partial reciprocal inclusion. Photoswitching to the Z-isomer disrupts the dimers into monomeric species, offering opportunity for the spatiotemporal control of the organizational status by light.
Melon shows a broad diversity in fruit morphology and quality, which is still underexploited in breeding programs. The knowledge of the genetic basis of fruit quality traits is important for ...identifying new alleles that may be introduced in elite material by highly efficient molecular breeding tools.
In order to identify QTLs controlling fruit quality, a recombinant inbred line population was developed using two commercial cultivars as parental lines: "Védrantais", from the cantalupensis group, and "Piel de Sapo", from the inodorus group. Both have desirable quality traits for the market, but their fruits differ in traits such as rind and flesh color, sugar content, ripening behavior, size and shape. We used a genotyping-by-sequencing strategy to construct a dense genetic map, which included around five thousand variants distributed in 824 bins. The RIL population was phenotyped for quality and morphology traits, and we mapped 33 stable QTLs involved in sugar and carotenoid content, fruit and seed morphology and major loci controlling external color of immature fruit and mottled rind. The median confidence interval of the QTLs was 942 kb, suggesting that the high density of the genetic map helped in increasing the mapping resolution. Some of these intervals contained less than a hundred annotated genes, and an integrative strategy combining gene expression and resequencing data enabled identification of candidate genes for some of these traits.
Several QTLs controlling fruit quality traits in melon were identified and delimited to narrow genomic intervals, using a RIL population and a GBS-based genetic map.
The only glaciers existing today in the Iberian Peninsula are small features located in the Pyrenees, though their number and extension has undergone significant changes over the Late Quaternary. The ...wide range of glacial landforms and deposits distributed across different Iberian ranges suggests the occurrence of several past periods with larger glacial systems. The objective of this research is to summarize the current knowledge on the spatial and temporal patterns of glacial activity in the Iberian mountains during the Late Quaternary. To this purpose, the chronological framework was divided in six periods: glaciations prior to the Last Glacial Cycle (Middle Pleistocene), Last Glacial Cycle (Late Pleistocene), Termination-1, Holocene, Little Ice Age (LIA) and present-day. The data were geographically divided considering the mountain systems where glacial evidence exists: Pyrenees, Cantabrian Range, NW ranges, Central Range, Iberian Range and Sierra Nevada. During Quaternary cold stages, ice accumulated in the head valleys of these mountain ranges and glaciers flowed down-valleys. In all cases, glaciers remained confined within the mountain systems and did not reach the surrounding lowlands. Depending on the combination of temperatures and moisture conditions, more or less ice was stored. In some ranges, there is evidence of Middle Pleistocene glaciations, one potentially correlating with marine isotope stage (MIS) 12 and another correlating with MIS 6 with glaciation dated to ca. 130-170 ka. However, most of the glacial records correspond to the Last Glacial Cycle and subsequent Termination. The maximum glacial expansion of this last Pleistocene glaciation stage occurred well before the global Last Glacial Maximum (LGM) between 30 and 60 ka in the Cantabrian Mountains and Pyrenees, at ca. 30 ka in Sierra Nevada and NW ranges, and (almost) synchronously to the LGM in the Central Range and Iberian Range. A massive glacial retreat occurred in all ranges at 19-20 ka, but the long-term deglaciation process was interrupted by cold intervals, such as the Oldest and Younger Dryas, which favoured glacial expansion in the highest mountains. Temperature increase recorded during the Holocene conditioned the melting of glaciers, which only reappeared in the highest massifs during the coldest periods, such as the LIA. However, post-LIA warming led to glacier disappearance in the Cantabrian Mountains, Sierra Nevada and most massifs of the Pyrenees, together with an accelerated shrinkage of the small glaciers still existing in this range at elevations near 3000 m.
Cyclodextrin-based gene delivery systems Ortiz Mellet, Carmen; García Fernández, José M; Benito, Juan M
Chemical Society reviews
40, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Cyclodextrin (CD) history has been largely dominated by their unique ability to form inclusion complexes with guests fitting in their hydrophobic cavity. Chemical funcionalization was soon recognized ...as a powerful mean for improving CD applications in a wide range of fields, including drug delivery, sensing or enzyme mimicking. However, 100 years after their discovery, CDs are still perceived as novel nanoobjects of undeveloped potential. This critical review provides an overview of different strategies to promote interactions between CD conjugates and genetic material by fully exploiting the inside-outside/upper-lower face anisotropy of the CD nanometric platform. Covalent modification, self-assembling and supramolecular ligation can be put forward with the ultimate goal to build artificial viruses for programmed and efficient gene therapy (222 references).
sp2-Iminosugar glycolipids (sp2-IGLs) represent a consolidated family of glycoconjugate mimetics encompassing a monosaccharide-like glycone moiety with a pseudoamide-type nitrogen replacing the ...endocyclic oxygen atom of carbohydrates and an axially-oriented lipid chain anchored at the pseudoanomeric position. The combination of these structural features makes them promising candidates for the treatment of a variety of conditions, spanning from cancer and inflammatory disorders to parasite infections. The exacerbated anomeric effect associated to the putative sp2-hybridized N-atom imparts chemical and enzymatic stability to sp2-IGLs and warrants total α-anomeric stereoselectivity in the key glycoconjugation step. A variety of O-, N-, C- and S-pseudoglycosides, differing in glycone configurational patterns and lipid nature, have been previously prepared and evaluated. Here we expand the chemical space of sp2-IGLs by reporting the synthesis of α-d-gluco-configured analogs with a bicyclic (5N,6O-oxomethylidene)nojirimycin (ONJ) core incorporating selenium at the glycosidic position. Structure–activity relationship studies in three different scenarios, namely cancer, Leishmaniasis and inflammation, convey that the therapeutic potential of the sp2-IGLs is highly dependent, not only on the length of the lipid chain (linear aliphatic C12 vs. C8), but also on the nature of the glycosidic atom (nitrogen vs. sulfur vs. selenium). The ensemble of results highlights the α-dodecylseleno-ONJ-glycoside as a promising multitarget drug candidate.
•Melatonin is synthesised by non-Saccharomyces strains.•Red Fruit strain produces more melatonin than others included in this study.•Non-Saccharomyces synthesised Tryptophan ethyl ester during the ...fermentation process.•Melatonin synthesis took place at end of the exponential growth phase.•Saccharomyces strains consumed Tryptophan faster than non-Saccharomyces.
Melatonin is a neurohormone involved in the regulation of circadian rhythms in humans. Evidence has recently been found of its occurrence in wines and its role in the winemaking process. The yeast Saccharomyces cerevisiae is consequently thought to be important in Melatonin synthesis, but limited data and reference texts are available on this synthetic pathway.
This paper aims to elucidate whether the synthetic pathway of Melatonin in Saccharomyces and non-Saccharomyces strains involves these intermediates. To this end, seven commercial strains comprising Saccharomyces cerevisiae (Red Fruit, ES488, Lalvin QA23, Uvaferm BC, and Lalvin ICV GRE) and non-Saccharomyces (Torulaspora delbrueckii and Metschnikowia pulcherrima) were monitored, under controlled fermentation conditions, in synthetic must, for seven days. Samples were analysed using a UHPLC—HRMS system (Qexactive).
Five out of the seven strains formed Melatonin during the fermentation process: three S. cerevisiae strains and the two non-Saccharomyces. Additionally, other compounds derived from l-tryptophan occurred during fermentation.
The discovery of charge-density-wave-related effects in the resonant inelastic x-ray scattering spectra of cuprates holds the tantalizing promise of clarifying the interactions that stabilize the ...electronic order. Here, we report a comprehensive resonant inelastic x-ray scattering study of La2−xSrxCuO4 finding that charge-density wave effects persist up to a remarkably high doping level of x=0.21 before disappearing at x=0.25. The inelastic excitation spectra remain essentially unchanged with doping despite crossing a topological transition in the Fermi surface. This indicates that the spectra contain little or no direct coupling to electronic excitations near the Fermi surface, rather they are dominated by the resonant cross section for phonons and charge-density-wave-induced phonon softening. We interpret our results in terms of a charge-density wave that is generated by strong correlations and a phonon response that is driven by the charge-density-wave-induced modification of the lattice.
The current COVID-19 pandemic has made patent the need for rapid and cost-effective diagnostic tests, crucial for future infectious outbreaks. Loop-mediated isothermal amplification (LAMP) is a ...promising and decentralized alternative to qPCR. In this work we have developed a sensitive, fast, and simple innovative methodology for quantification of SARS-CoV-2 RNA copies, combining reverse-transcription LAMP with electrochemical detection. This is based on the oxidation of phenol red (PR), a visual and electroactive LAMP indicator, which oxidation peak potential (Ep) changes with the progress of the LAMP reaction. Using that Ep shift as analytical signal, a calibration curve was obtained for fragment N1 copies of SARS-CoV2 (which provided better results than N or S fragments), with a potential shift of 16.2 mV per order of magnitude, and a practical limit of detection of 21 copies·μL−1. Moreover, the precision of Ep is excellent (RSD < 2%): 557 ± 5 mV for negative and 602 ± 7 mV for positive (2148 N fragment RNA copies·µL-1·-1) LAMP controls. This methodology has been applied to the analysis of nasopharyngeal swab samples, resulting in total concordance with clinical RT-qPCR results. Advances towards fully decentralization have been achieved by designing and fabricating a small portable heater for isothermal procedures, obtaining comparable results to those from a commercial benchtop thermal cycler.
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•The electrochemical process of phenol red is used for quantitating LAMP reactions.•SARS-CoV-2 copies are quantitated by RT-LAMP with electrochemical detection.•21 copies of SARS-CoV-2 are detected electrochemically in 40 min by RT-LAMP.•A quantitative SARS-CoV-2 RT-LAMP method has been developed without extra reagents.•A portable LAMP heater has been developed to decentralize SARS-CoV-2 detection.
We generated mice deficient in Lon protease (LONP1), a major enzyme of the mitochondrial quality control machinery. Homozygous deletion of Lonp1 causes early embryonic lethality, whereas its ...haploinsufficiency protects against colorectal and skin tumors. Furthermore, LONP1 knockdown inhibits cellular proliferation and tumor and metastasis formation, whereas its overexpression increases tumorigenesis. Clinical studies indicate that high levels of LONP1 are a poor prognosis marker in human colorectal cancer and melanoma. Additionally, functional analyses show that LONP1 plays a key role in metabolic reprogramming by remodeling OXPHOS complexes and protecting against senescence. Our findings demonstrate the relevance of LONP1 for cellular and organismal viability and identify this protease as a central regulator of mitochondrial activity in oncogenesis.
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•LONP1 is a mitochondrial protease essential for embryonic development•LONP1 is upregulated in human colorectal and melanoma tumors•Loss of LONP1 induces mitochondrial dysfunction and triggers cellular senescence•LONP1 regulates metabolic reprogramming through remodeling mitochondrial function
In this study, Quiros et al. identify LONP1 as an essential gatekeeper protease for ensuring cellular and organismal fitness. LONP1 deficiency causes embryonic lethality in mice, and haploinsufficiency protects against colorectal and skin tumors. LONP1 participates in OXPHOS remodeling and allows efficient mitochondrial and cellular reprogramming, thus facilitating the tumorigenic properties of cancer cells. This study provides essential functional knowledge about LONP1 and suggests new opportunities for therapeutic intervention in cancer.
Inflammatory processes play a central role in the pathogenesis of diabetic nephropathy (DN) in the early stages of the disease. The authors demonstrate that the glycolipid mimetic (Ss)-DS-ONJ is able ...to abolish inflammation via the induction of autophagy flux and provokes the inhibition of inflammasome complex in ex vivo and in vitro models, using adult kidney explants from BB rats. The contribution of (Ss)-DS-ONJ to reducing inflammatory events is mediated by the inhibition of classical stress kinase pathways and the blocking of inflammasome complex activation. The (Ss)-DS-ONJ treatment is able to inhibit the epithelial-to-mesenchymal transition (EMT) progression, but only when the IL18 levels are reduced by the treatment. These findings suggest that (Ss)-DS-ONJ could be a novel, and multifactorial treatment for DN.
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