ABSTRACT
Objective: To review the hoaxes' characteristics spread through WhatsApp in Spain during COVID-19 lockdown and identify what kind of substances were promoted for consumption or application. Method: A phone number was activated to receive hoaxes via WhatsApp. A total of 2353 messages were collected, and among those 584 different hoaxes were identified and validated, between March 18 and April 18, 2020. From these 584 hoaxes, a sub-sample of 126 was selected, exclusively related to the object of study, and a content analysis table with fourteen registration fields was applied. Besides, the averages and medians of the quantitative fields were extracted. Results: Most of the messages received were texts (39%) and videos (30%). In the majority, the acting subject was presented as medical personnel (36.5%) or as an anonymous person (30.9%). The videos lasted between 2' 40 and 18' 18, while the audios ranged between 1' 35 and 7' 48. Regarding the gender of the informant, there was a significant difference, with 45.2% being male, and 13.5%, female and 41.3% non-identifiable. Conclusions: One out of five false health claims received was about prevention or cure of the coronavirus, based on the principle of medical authority, and basically promoting the use and consumption of substances of natural origin. (AUº)
Objetivo: Examinar las características de los bulos difundidos por WhatsApp en España durante el confinamiento por la pandemia de COVID-19 e identificar qué tipo de sustancias se promovieron para su ingesta o uso. Método: Se habilitó un número de teléfono para recibir bulos por WhatsApp. Se recibieron 2353 mensajes, de los que se identificaron y validaron 584 bulos distintos, entre el 18 de marzo y el 18 de abril de 2020. De los 584 bulos, se seleccionó una submuestra de 126 relacionados con el objeto de estudio y se aplicó una ficha de análisis de contenido con 14 campos de registro. Además, se extrajeron las medias y medianas de los campos cuantitativos. Resultados: La mayor parte de los mensajes fueron cadenas de texto (39%) y vídeos (30%). En la mayoría, el sujeto se presentaba como personal médico (36,5%) o como persona anónima (30,9%). Los vídeos tuvieron una duración de entre 2' 40 y 18' 18, mientras que los audios fueron de entre 1' 35 y 7' 48. Con respecto al sexo, se apreció una gran diferencia: el 45,2% de los protagonistas fueron hombres, frente al 13,5% de mujeres; el 41,3% no era identificable. Conclusiones: Uno de cada cinco bulos recibidos fue sobre prevención o curación del coronavirus, argumentados sobre el principio de autoridad médica y básicamente promoviendo el uso y consumo de sustancias de origen natural. (AU)
Subject(s)
Pandemics , Coronavirus Infections/epidemiology , Spain , Severe acute respiratory syndrome-related coronavirus , Communicable Disease Control , DeceptionABSTRACT
OBJECTIVE: To review the hoaxes' characteristics spread through WhatsApp in Spain during COVID-19 lockdown and identify what kind of substances were promoted for consumption or application. METHOD: A phone number was activated to receive hoaxes via WhatsApp. A total of 2353 messages were collected, and among those 584 different hoaxes were identified and validated, between March 18 and April 18, 2020. From these 584 hoaxes, a sub-sample of 126 was selected, exclusively related to the object of study, and a content analysis table with fourteen registration fields was applied. Besides, the averages and medians of the quantitative fields were extracted. RESULTS: Most of the messages received were texts (39%) and videos (30%). In the majority, the acting subject was presented as medical personnel (36.5%) or as an anonymous person (30.9%). The videos lasted between 2' 40" and 18' 18", while the audios ranged between 1' 35" and 7' 48". Regarding the gender of the informant, there was a significant difference, with 45.2% being male, and 13.5%, female and 41.3% non-identifiable. CONCLUSIONS: One out of five false health claims received was about prevention or cure of the coronavirus, based on the principle of medical authority, and basically promoting the use and consumption of substances of natural origin.
Subject(s)
COVID-19 , Communicable Disease Control , Deception , Female , Humans , Male , SARS-CoV-2 , SpainABSTRACT
OBJETIVO: Examinar las características de los bulos difundidos por WhatsApp en España durante el confinamiento por la pandemia de COVID-19 e identificar qué tipo de sustancias se promovieron para su ingesta o uso. MÉTODO: Se habilitó un número de teléfono para recibir bulos por WhatsApp. Se recibieron 2353 mensajes, de los que se identificaron y validaron 584 bulos distintos, entre el 18 de marzo y el 18 de abril de 2020. De los 584 bulos, se seleccionó una submuestra de 126 relacionados con el objeto de estudio y se aplicó una ficha de análisis de contenido con 14 campos de registro. Además, se extrajeron las medias y medianas de los campos cuantitativos. RESULTADOS: La mayor parte de los mensajes fueron cadenas de texto (39%) y vídeos (30%). En la mayoría, el sujeto se presentaba como personal médico (36,5%) o como persona anónima (30,9%). Los vídeos tuvieron una duración de entre 2' 40" y 18' 18", mientras que los audios fueron de entre 1' 35" y 7' 48". Con respecto al sexo, se apreció una gran diferencia: el 45,2% de los protagonistas fueron hombres, frente al 13,5% de mujeres; el 41,3% no era identificable. CONCLUSIONES: Uno de cada cinco bulos recibidos fue sobre prevención o curación del coronavirus, argumentados sobre el principio de autoridad médica y básicamente promoviendo el uso y consumo de sustancias de origen natural
OBJECTIVE: To review the hoaxes' characteristics spread through WhatsApp in Spain during COVID-19 lockdown and identify what kind of substances were promoted for consumption or application. METHOD: A phone number was activated to receive hoaxes via WhatsApp. A total of 2353 messages were collected, and among those 584 different hoaxes were identified and validated, between March 18 and April 18, 2020. From these 584 hoaxes, a sub-sample of 126 was selected, exclusively related to the object of study, and a content analysis table with fourteen registration fields was applied. Besides, the averages and medians of the quantitative fields were extracted. RESULTS: Most of the messages received were texts (39%) and videos (30%). In the majority, the acting subject was presented as medical personnel (36.5%) or as an anonymous person (30.9%). The videos lasted between 2' 40" and 18' 18", while the audios ranged between 1' 35" and 7' 48". Regarding the gender of the informant, there was a significant difference, with 45.2% being male, and 13.5%, female and 41.3% non-identifiable. CONCLUSIONS: One out of five false health claims received was about prevention or cure of the coronavirus, based on the principle of medical authority, and basically promoting the use and consumption of substances of natural origin
Subject(s)
Humans , Coronavirus Infections/epidemiology , Quackery/statistics & numerical data , Pandemics/statistics & numerical data , Social Networking , Access to Information/ethics , Information Dissemination/ethics , Health Communication/methodsABSTRACT
Fluorescent dye labeling of DNA oligonucleotides and nanostructures is one of the most used techniques to track their fate and cellular localization inside cells. Here, we report that intracellular fluorescence, and even FRET signals, cannot be correlated with the cellular uptake of intact DNA structures. Live cell imaging revealed high colocalization of cyanine-labeled DNA oligos and nanostructures with phosphorylated small-molecule cyanine dyes, one of the degradation products from these DNA compounds. Nuclease degradation of the strands outside and inside the cell results in a misleading intracellular fluorescent signal. The signal is saturated by the fluorescence of the degradation product (phosphorylated dye). To test our hypothesis, we synthesized a range of DNA structures, including Cy3- and Cy5-labeled DNA cubes and DNA tetrahedra, and oligonucleotides with different stabilities toward nucleases. All give fluorescence signals within the mitochondria after cellular uptake and strongly colocalize with a free phosphorylated dye control. Kinetics experiments revealed that uptake of stable DNA structures is delayed. We also studied several parameters influencing fluorescent data: stability of the DNA strand, fixation methods that can wash away the signal, position of the dye on the DNA strand, and design of FRET experiments. DNA nanostructures hold tremendous potential for biomedical applications and biotechnology because of their biocompatibility, programmability, and easy synthesis. However, few examples of successful DNA machines in vivo have been reported. We believe this contribution can be used as a guide to design better cellular uptake experiments when using fluorescent dyes, in order to further propel the biological development, and application of DNA nanostructures.
ABSTRACT
Recently, we studied glucose-nucleobase pairs, a binding motif found in aminoglycoside-RNA recognition. DNA duplexes with glucose as a nucleobase were able to hybridize and were selective for purines. They were less stable than natural DNA but still fit well on regular B-DNA. These results opened up the possible use of glucose as a non-aromatic DNA base mimic. Here, we have studied the incorporation and thermal stability of glucose with different types of anchoring units and alternative apolar sugar-nucleobase pairs. When we explored butanetriol instead of glycerol as a wider anchoring unit, we did not gain duplex thermal stability. This result confirmed the necessity of a more conformationally restricted linker to increase the overall duplex stability. Permethylated glucose-nucleobase pairs showed similar stability to glucoside-nucleobase pairs but no selectivity for a specific nucleobase, possibly due to the absence of hydrogen bonds between them. The three-dimensional structure of the duplex solved by NMR located both, the hydrophobic permethylated glucose and the nucleobase, inside the DNA helix as in the case of glucose-nucleobase pairs. Quantum chemical calculations on glucose-nucleobase pairs indicate that the attachment of the sugar to the DNA skeleton through the OH1 or OH4 positions yields the highest binding energies. Moreover, glucose was very selective for guanine when attached through OH1 or OH4 to the DNA. Finally, we examined DNA polymerase insertion of nucleotides in front of the saccharide unit. KF- polymerase from E. coli inserted A and G opposite glc and 6dglc with low efficiency but notable selectivity. It is even capable of extending the new pair although its efficiency depended on the DNA sequence. In contrast, Bst 2.0, SIII and BIOTAQ™ DNA polymerases seem to display a loop-out mechanism possibly due to the flexible glycerol linker used instead of deoxyribose.
ABSTRACT
Natural systems combine different supramolecular interactions in a hierarchical manner to build structures. In contrast, DNA nanotechnology relies almost exclusively on DNA base pairing for structure generation. Introducing other supramolecular interactions can expand the structural and functional range of DNA assemblies, but this requires an understanding of the interplay between these interactions. Here, an economic strategy to build DNA nanotubes functionalized with lipid-like polymers is reported. When these polymers are linked to the nanotube using a spacer, they fold inside to create a hydrophobic environment within the nanotube; the nanotube can encapsulate small molecules and conditionally release them when specific DNA strands are added, as monitored by single-molecule fluorescence microscopy. When the polymers are directly linked to the nanostructure without spacers, they interact intermolecularly to form a network of DNA bundles. This morphological switch can be directly observed using a strand displacement strategy. The two association modes result in different cellular uptake behavior. Nanotubes with internal hydrophobic association show dye-mediated mitochondrial colocalization inside cells; while the bundles disassemble into smaller polymer-coated structures that reduce the extent of nonspecific cellular uptake. This approach uncovers parameters to direct the hierarchical assembly of DNA nanostructures, and produces promising materials for targeted drug delivery.
Subject(s)
Coated Materials, Biocompatible , DNA , Drug Delivery Systems/methods , Nanotubes/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , DNA/chemistry , DNA/pharmacology , HeLa Cells , Humans , Hydrophobic and Hydrophilic Interactions , Nanotechnology/methodsABSTRACT
A library of 5-arylthiosubstituted 2-amino-4,6-diaryl-3-cyano-4H-pyrans has been synthesized as a new family of non-peptide NK1 receptor ligands by a one-pot cascade process. Their biological effects via interaction with the NK1 receptor were experimentally determined as percentage of inhibition (for antagonists) and percentage of activation (for agonists), compared to the substance P (SP) effect, in IPone assay. A set of these amino compounds was found to inhibit the action of SP, and therefore can be considered as a new family of SP-antagonists. Interestingly, the acylation of the 2-amino position causes a switch from antagonist to agonist activity. The 5-phenylsulfonyl-2-amino derivative 17 showed the highest antagonist activity, while the 5-p-tolylsulfenyl-2-trifluoroacetamide derivative 20R showed the highest agonist effect. As expected, in the case of the 5-sulfinylderivatives, there was an enantiomeric discrimination in favor of one of the two enantiomers, specifically those with (SS,RC) configuration. The anticancer activity studies assessed by using human A-549 lung cancer cells and MRC-5 non-malignant lung fibroblasts, revealed a statistically significant selective cytotoxic effect of some of these 2-amino-4H-pyran derivatives toward the lung cancer cells. These studies demonstrated that the newly synthesized 4H-pyran derivatives can be used as a starting point for the synthesis of novel SP-antagonists with higher anticancer activity in the future.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Neurokinin-1 Receptor Antagonists/pharmacology , Pyrans/pharmacology , Receptors, Neurokinin-1/agonists , Receptors, Neurokinin-1/metabolism , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Ligands , Molecular Structure , Neurokinin-1 Receptor Antagonists/chemical synthesis , Neurokinin-1 Receptor Antagonists/chemistry , Pyrans/chemical synthesis , Pyrans/chemistry , Structure-Activity RelationshipABSTRACT
Galactose-modified thymidine, LNA-T, and 2'-amino-LNA-T nucleosides were synthesized, converted into the corresponding phosphoramidite derivatives and introduced into short oligonucleotides. Compared to the unmodified control strands, the galactose-modified oligonucleotides in general, and the N2'-functionalized 2'-amino-LNA derivatives in particular, showed improved duplex thermal stability against DNA and RNA complements and increased ability to discriminate mismatches. In addition, the 2'-amino-LNA-T derivatives induced remarkable 3'-exonuclease resistance. These results were further investigated using molecular modeling studies.
Subject(s)
DNA/chemistry , Galactose/chemistry , Oligonucleotides/chemistry , Biophysical Phenomena , Carbon-13 Magnetic Resonance Spectroscopy , Models, Molecular , Nucleic Acid Denaturation , Proton Magnetic Resonance Spectroscopy , Spectrometry, Mass, Electrospray Ionization , TemperatureABSTRACT
Noncovalent forces rule the interactions between biomolecules. Inspired by a biomolecular interaction found in aminoglycoside-RNA recognition, glucose-nucleobase pairs have been examined. Deoxyoligonucleotides with a 6-deoxyglucose insertion are able to hybridize with their complementary strand, thus exhibiting a preference for purine nucleobases. Although the resulting double helices are less stable than natural ones, they present only minor local distortions. 6-Deoxyglucose stays fully integrated in the double helix and its OH groups form two hydrogen bonds with the opposing guanine. This 6-deoxyglucose-guanine pair closely resembles a purine-pyrimidine geometry. Quantum chemical calculations indicate that glucose-purine pairs are as stable as a natural T-A pair.
Subject(s)
DNA/metabolism , Deoxyglucose/analogs & derivatives , N-Glycosyl Hydrolases/metabolism , Base Pairing , DNA/chemistry , Deoxyglucose/chemistry , Deoxyglucose/metabolism , Guanine/chemistry , Guanine/metabolism , Hydrogen Bonding , Magnetic Resonance Spectroscopy , N-Glycosyl Hydrolases/chemistry , Nucleic Acid Conformation , Paromomycin/chemistry , Paromomycin/metabolism , Quantum Theory , Thermodynamics , Transition TemperatureABSTRACT
Carbohydrate-aromatic interactions are highly relevant for many biological processes. Nevertheless, experimental data in aqueous solution relating structure and energetics for sugar-arene stacking interactions are very scarce. Here, we evaluate how structural variations in a monosaccharide including carboxyl, N-acetyl, fluorine, and methyl groups affect stacking interactions with aromatic DNA bases. We find small differences on stacking interaction among the natural carbohydrates examined. The presence of fluorine atoms within the pyranose ring slightly increases the interaction with the C-G DNA base pair. Carbohydrate hydrophobicity is the most determinant factor. However, gradual increase in hydrophobicity of the carbohydrate does not translate directly into a steady growth in stacking interaction. The energetics correlates better with the amount of apolar surface buried upon sugar stacking on top of the aromatic DNA base pair.
Subject(s)
Carbohydrates/chemistry , DNA/chemistry , Hydrocarbons, Fluorinated/chemistry , Water/chemistry , Base Pairing , Hydrophobic and Hydrophilic Interactions , Magnetic Resonance Spectroscopy , Models, Molecular , ThermodynamicsABSTRACT
Oligoribonucleotide conjugates carrying apolar carbohydrates at the 5'-end and the corresponding siRNA duplexes have been prepared using phosphoramidite chemistry. All the carbohydrate-siRNA derivatives were compatible with RNA interference machinery if transfected with oligofectamine. In the absence of a transfection agent, some of them exerted certain reduction of gene expression. Double-tailed permethylated glucose conjugated to siRNA through a long spacer inhibited gene expression up to 26% compared to the scrambled duplex. Such modifications contribute positively to the stability of oligoribonucleotides against 5'-exonuclease degradation.
Subject(s)
Carbohydrates/chemistry , RNA, Small Interfering/chemical synthesis , Animals , HeLa Cells , Humans , Luciferases, Renilla/antagonists & inhibitors , Luciferases, Renilla/genetics , Luciferases, Renilla/metabolism , Phosphodiesterase I/metabolism , RNA Interference , RNA, Small Interfering/metabolism , Renilla/enzymology , TransfectionABSTRACT
Quadruplex DNA structures are attracting an enormous interest in many areas of chemistry, ranging from chemical biology, supramolecular chemistry to nanoscience. We have prepared carbohydrate-DNA conjugates containing the oligonucleotide sequences of G-quadruplexes (thrombin binding aptamer (TBA) and human telomere (TEL)), measured their thermal stability and studied their structure in solution by using NMR and molecular dynamics. The solution structure of a fucose-TBA conjugate shows stacking interactions between the carbohydrate and the DNA G-tetrad in addition to hydrogen bonding and hydrophobic contacts. We have also shown that attaching carbohydrates at the 5'-end of a quadruplex telomeric sequence can alter its folding topology. These results suggest the possibility of modulating the folding of the G-quadruplex by linking carbohydrates and have clear implications in molecular recognition and the design of new G-quadruplex ligands.
Subject(s)
Aptamers, Nucleotide/chemistry , Carbohydrates/chemistry , DNA/chemistry , Telomere/chemistry , Aptamers, Nucleotide/metabolism , DNA/metabolism , G-Quadruplexes , Humans , Hydrogen Bonding , Ligands , Magnetic Resonance Spectroscopy , Molecular Structure , Solutions , Telomere/metabolismABSTRACT
Mono- and disaccharides have been shown to stack on top of DNA duplexes stabilizing sequences with terminal C-G base pairs. Here we present an apolar version of glucose and cellobiose as new capping agents that stack on DNA increasing considerably its stability with respect to their natural polyhydroxylated mono- and disaccharide DNA conjugates.