Characterization of Several Small Biologically Relevant Molecules by Infrared Multiple Photon Dissociation Spectroscopy and Electronic Structure Calculations

Infrared multiple photon dissociation (IRMPD) spectroscopy has been coupled with electronic structure calculations in order to elucidate the structures of several small biological molecules including: uracil, 5-fluorouracil, 5-fluorocytosine, ferulic acid, and a number of their related analogs. IRMPD is a powerful technique, that when combined with electronic structure calculations can provide convincing evidence for the structural characterization of ions in the gas phase. Isomers of uracil and 5-fluorouracil (5-FU) have been characterized by calculations performed at the MP2(full)/aug-cc-pVTZ level of theory; however, infrared multiple photon dissociation spectroscopy experiments proved to be unsuccessful for these species. Geometry optimization and frequency calculations have isolated the dominant isomer(s) for neutral and deprotonated uracil and 5-fluorouracil, along with several cluster interactions involving water, methanol, ammonia, and methylamine. For both uracil and 5-FU, a single relevant neutral isomer was determined, with each isomer existing in the diketo, as opposed to the enol form. Following the deprotonation of this neutral isomer, both uracil and 5-FU were permitted to form anionic cluster ions with water, methanol, ammonia, or methylamine, and based on the relative Gibbs free energies (298 K) of the calculated isomers, relevant cluster interactions were determined. For each cluster, several sites of intramolecular interaction were found to exist; however, interaction at the site of deprotonation was the most favourable in every instance. Ionic hydrogen bond interactions have been found in several clusters formed by 5-fluorocytosine (5-FC). The chloride and trimethylammonium cluster ions, in addition to the cationic and anionic dimers have been characterized by infrared multiple photon dissociation (IRMPD) spectroscopy and electronic structure calculations performed at the B2PLYP/aug-cc-pVTZ//B3LYP/6-311+G(d,p) level of theory. IRMPD spectra in combination with calculated spectra and relative energetics have indicated, quite conclusively, that a single isomer for each 5-FC cluster that is likely being observed experimentally except in the case of the anionic dimer, in which a combination of isomers is probable. For the 5-FC-trimethylammonium cluster specifically, the calculated spectrum of the lowest energy isomer matches the experimental spectrum remarkably well. Interestingly, the cationic dimer of 5-FC was found to have a single energetically relevant isomer (Cationic-IV) in which a unique tridentate ionic hydrogen bond interaction is formed. The three sites of intramolecular ionic hydrogen bonds in this isomer interact very efficiently, leading to a significantly large calculated enthalpy of binding of 180 kJ/mol. The magnitude of the calculated binding energy for this species, in combination with the strong correlation between the simulated and IRMPD spectra, indicates that the tridentate-bound dimer is observed predominantly in experiment. Comparison of the calculated relative Gibbs free energies (298 K) for this species with several of the other isomers considered also supports the likelihood of the dominant protonated dimer existing as Cationic-IV. Protonated ferulic acid has been characterized using infrared multiple photon dissociation spectroscopy and electronic structure calculations at the B3LYP/6-311+G(d,p) level of theory. Neutral ferulic acid has been determined to undergo protonation on the carbonyl oxygen of the acid group, forming an ion of m/z 195. Due to its extensively conjugated structure, protonated ferulic acid (m/z 195) is observed to yield three stable fragment ions in IRMPD experiments. It is proposed that two parallel fragmentation pathways of protonated ferulic acid are being observed. First, proton transfer occurs from the carbonyl oxygen to the hydroxyl oxygen within the acid group, resulting in the loss of water and subsequently carbon monoxide, forming ions of m/z 177 and 149, respectively. The second proposed fragmentation pathway undergoes proton transfer from the phenolic group to the methoxy group resulting in loss of methanol and rearrangement to a five-membered ring of m/z 163. IRMPD spectra have been obtained for the ions m/z 195 and m/z 177, and anharmonic calculations have been performed on these species at the B3LYP/6-311+G(d,p) level of theory. The calculated anharmonic spectra for these ions match the experimental spectrum exceptionally well and strongly support the proposed fragmentation mechanisms

Image formation in the scanning helium microscope

The scanning helium microscope (SHeM) is a new addition to the array of available microscopies, particularly for delicate materials that may suffer damage under techniques utilising light or charged particles. As with all other microscopies, the specifics of image formation within the instrument are required to gain a full understanding of the produced micrographs. We present work detailing the basics of the subject for the SHeM, including the specific nature of the projection distortions that arise due to the scattering geometry. Extension of these concepts allowed for an iterative ray tracing Monte Carlo model replicating diffuse scattering from a sample surface to be constructed. Comparisons between experimental data and simulations yielded a minimum resolvable step height of (67 ± 5) µm and a minimum resolvable planar angle of (4.3 ± 0.3)° for the instrument in question.acceptedVersio

Atg4 proteolytic activity can be inhibited by Atg1 phosphorylation

The biogenesis of autophagosomes depends on the conjugation of Atg8-like proteins with phosphatidylethanolamine. Atg8 processing by the cysteine protease Atg4 is required for its covalent linkage to phosphatidylethanolamine, but it is also necessary for Atg8 deconjugation from this lipid to release it from membranes. How these two cleavage steps are coordinated is unknown. Here we show that phosphorylation by Atg1 inhibits Atg4 function, an event that appears to exclusively occur at the site of autophagosome biogenesis. These results are consistent with a model where the Atg8-phosphatidylethanolamine pool essential for autophagosome formation is protected at least in part by Atg4 phosphorylation by Atg1 while newly synthesized cytoplasmic Atg8 remains susceptible to constitutive Atg4 processing

PAPEL DA INTELIGÊNCIA ARTIFICIAL NA PREDIÇÃO DE EVENTOS CARDÍACOS

Artificial Intelligence (AI) plays a crucial role in predicting cardiac events, offering advanced analytical tools to evaluate medical data. By processing large sets of information, AI identifies subtle patterns, enabling early detection of potential heart risks. This innovative approach not only improves diagnostic accuracy but also contributes to more effective preventive interventions by promoting proactive management of cardiovascular health. Objectives: Explore the crucial role played by artificial intelligence in predicting cardiac events. Methodology: Data collection was conducted through the following databases: Nursing Database (BDENF), Scientific Electronic Library Online (SCIELO), PubMed, Latin American Caribbean Literature in Health Sciences (LILACS). Various types of publications were consulted, including scientific articles, monographs and magazines, with the aim of obtaining relevant information on the topic. Results and Discussions: The effectiveness of Artificial Intelligence in predicting cardiac events, demonstrating remarkable accuracy rates and an ability to identify complex patterns in medical data. This approach offers a promising prospect for improving the prevention and management of cardiac conditions. In the discussion, it is relevant to consider potential challenges, such as clinical interpretation of results and the continued need for large-scale validation. The integration of AI into clinical practice suggests significant advances, but ethical and regulatory issues also deserve attention to ensure the responsible implementation of this technology. Conclusion: In summary, the use of Artificial Intelligence in predicting cardiac events demonstrates promising effectiveness, providing valuable insights for medical practice. While the results are encouraging, it is imperative to continue refining and validating these approaches while carefully considering ethical and regulatory aspects. The potential positive impact of AI on cardiovascular health is evident, pointing to significant developments in the prevention and treatment of heart conditions.A Inteligência Artificial (IA) desempenha um papel crucial na predição de eventos cardíacos, oferecendo avançadas ferramentas analíticas para avaliar dados médicos. Ao processar grandes conjuntos de informações, a IA identifica padrões sutis, permitindo uma detecção precoce de potenciais riscos cardíacos. Esta abordagem inovadora não apenas aprimora a precisão diagnóstica, mas também contribui para intervenções preventivas mais eficazes, promovendo uma gestão proativa da saúde cardiovascular. Objetivos: Explorar o papel crucial desempenhado pela inteligência artificial na predição de eventos cardíacos. Materiais e Métodos: A coleta de dados foi conduzida por meio dos bancos de dados: Base de Dados em Enfermagem (BDENF), Scientific Electronic Library Online (SCIELO), PubMed, Literatura Latino-Americana do Caribe em Ciências da Saúde (LILACS). Foram consultados diversos tipos de publicações, incluindo artigos científicos, monografias e revistas, com o objetivo de obter informações relevantes sobre o tema. Resultados e Discussões: A eficácia da Inteligência Artificial na predição de eventos cardíacos, evidenciando taxas de acertos notáveis e uma capacidade de identificar padrões complexos nos dados médicos. Essa abordagem oferece uma perspectiva promissora para melhorar a prevenção e o gerenciamento de condições cardíacas. Na discussão, é relevante considerar desafios potenciais, como a interpretação clínica dos resultados e a necessidade contínua de validação em larga escala. A integração da IA na prática clínica sugere avanços significativos, mas questões éticas e regulatórias também merecem atenção para garantir a implementação responsável dessa tecnologia. Conclusão: Em resumo, a utilização da Inteligência Artificial na predição de eventos cardíacos demonstra promissora eficácia, proporcionando insights valiosos para a prática médica. Embora os resultados sejam encorajadores, é imperativo continuar refinando e validando essas abordagens, considerando cuidadosamente os aspectos éticos e regulatórios. O potencial impacto positivo da IA na saúde cardiovascular é evidente, apontando para uma evolução significativa na prevenção e no tratamento de condições cardíacas

Heart transplantation surgery in children and young adults with congenital heart disease

Abstract Background Pediatric cardiac transplantation remains a surgical challenge as a variety of cardiac and vessel malformation are present in patients with congenital heart disease (CHD). Despite limited availability and acceptability of donor hearts, the number of heart transplantations remains on a stable level with improved survival and quality of life. Observation As treatment options for CHD continue to improve and the chances of survival increase, more adult CHD patients are listed for transplantation. This review focuses on the clinical challenges and modified techniques of pediatric heart transplantations. Conclusion Not only knowledge of the exact anatomy, but above all careful planning, interdisciplinary cooperation and surgical experience are prerequisites for surgical success

Impact of Different In Vitro Electron Donor/Acceptor Conditions on Potential Chemolithoautotrophic Communities from Marine Pelagic Redoxclines

Anaerobic or microaerophilic chemolithoautotrophic bacteria have been considered to be responsible for CO(2) dark fixation in different pelagic redoxclines worldwide, but their involvement in redox processes is still not fully resolved. We investigated the impact of 17 different electron donor/acceptor combinations in water of pelagic redoxclines from the central Baltic Sea on the stimulation of bacterial CO(2) dark fixation as well as on the development of chemolithoautotrophic populations. In situ, the highest CO(2) dark fixation rates, ranging from 0.7 to 1.4 μmol liter(−1) day(−1), were measured directly below the redoxcline. In enrichment experiments, chemolithoautotrophic CO(2) dark fixation was maximally stimulated by the addition of thiosulfate, reaching values of up to 9.7 μmol liter(−1) CO(2) day(−1). Chemolithoautotrophic nitrate reduction proved to be an important process, with rates of up to 33.5 μmol liter(−1) NO(3)(−) day(−1). Reduction of Fe(III) or Mn(IV) was not detected; nevertheless, the presence of these potential electron acceptors influenced the development of stimulated microbial assemblages. Potential chemolithoautotrophic bacteria in the enrichment experiments were displayed on 16S ribosomal complementary DNA single-strand-conformation polymorphism fingerprints and identified by sequencing of excised bands. Sequences were closely related to chemolithoautotrophic Thiomicrospira psychrophila and Maorithyas hadalis gill symbiont (both Gammaproteobacteria) and to an uncultured nitrate-reducing Helicobacteraceae bacterium (Epsilonproteobacteria). Our data indicate that this Helicobacteraceae bacterium could be of general importance or even a key organism for autotrophic nitrate reduction in pelagic redoxclines

Image formation in the scanning helium microscope

The scanning helium microscope (SHeM) is a new addition to the array of available microscopies, particularly for delicate materials that may suffer damage under techniques utilising light or charged particles. As with all other microscopies, the specifics of image formation within the instrument are required to gain a full understanding of the produced micrographs. We present work detailing the basics of the subject for the SHeM, including the specific nature of the projection distortions that arise due to the scattering geometry. Extension of these concepts allowed for an iterative ray tracing Monte Carlo model replicating diffuse scattering from a sample surface to be constructed. Comparisons between experimental data and simulations yielded a minimum resolvable step height of (67 ± 5) µm and a minimum resolvable planar angle of (4.3 ± 0.3)° for the instrument in question

Taxonomy through the lens of neutral helium microscopy

The field of taxonomy is critically important for the identification, conservation, and ecology of biological species. Modern taxonomists increasingly need to employ advanced imaging techniques to classify organisms according to their observed morphological features. Moreover, the generation of three-dimensional datasets is of growing interest; moving beyond qualitative analysis to true quantitative classification. Unfortunately, biological samples are highly vulnerable to degradation under the energetic probes often used to generate these datasets. Neutral atom beam microscopes avoid such damage due to the gentle nature of their low energy probe, but to date have not been capable of producing three-dimensional data. Here we demonstrate a means to recover the height information for samples imaged in the scanning helium microscope (SHeM) via the process of stereophotogrammetry. The extended capabilities, namely sparse three-dimensional reconstructions of features, were showcased via taxonomic studies of both flora (Arabidopsis thaliana) and fauna (Heterodontus portusjacksoni). In concert with the delicate nature of neutral helium atom beam microscopy, the stereophotogrammetry technique provides the means to derive comprehensive taxonomical data without the risk of sample degradation due to the imaging process

Taxonomy through the lens of neutral helium microscopy

Abstract The field of taxonomy is critically important for the identification, conservation, and ecology of biological species. Modern taxonomists increasingly need to employ advanced imaging techniques to classify organisms according to their observed morphological features. Moreover, the generation of three-dimensional datasets is of growing interest; moving beyond qualitative analysis to true quantitative classification. Unfortunately, biological samples are highly vulnerable to degradation under the energetic probes often used to generate these datasets. Neutral atom beam microscopes avoid such damage due to the gentle nature of their low energy probe, but to date have not been capable of producing three-dimensional data. Here we demonstrate a means to recover the height information for samples imaged in the scanning helium microscope (SHeM) via the process of stereophotogrammetry. The extended capabilities, namely sparse three-dimensional reconstructions of features, were showcased via taxonomic studies of both flora (Arabidopsis thaliana) and fauna (Heterodontus portusjacksoni). In concert with the delicate nature of neutral helium atom beam microscopy, the stereophotogrammetry technique provides the means to derive comprehensive taxonomical data without the risk of sample degradation due to the imaging process

Calcium channel blockers and clinical outcomes in patients with continuous‐flow left ventricular assist devices

Abstract Aims Current guidelines suggest calcium channel blockers (CCBs) as the second or third option for blood pressure management in patients with left ventricular assist device (LVAD). However, the clinical outcomes of patients with LVAD who receive CCBs remain unclear. Our study aims to analyse the association of CCBs with clinical outcomes in patients after LVAD implantation. Methods and results This is a retrospective analysis based on the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2006 to 2017, and adult patients who were alive with LVAD and CCB treatment information at 6 months after implantation were included. Among 10 717 patients, 1369 received CCBs 6 months after implantation, and there was an increasing trend of CCB use after LVAD. Patients receiving CCB therapy at 6 months had a similar 5 year survival rate to those not receiving CCB [49.6%, 95% confidence interval (CI): 47.5–51.7% vs. 51.1%, 95% CI: 45.3–56.7%]. In both Cox and competing risk regressions after adjusting for confounding factors, CCB treatment at 6 months after implantation was not associated with long‐term mortality [hazard ratio (HR): 1.03, 95% CI: 0.91–1.17, P = 0.624 and subdistribution HR (SHR): 1.07, 95% CI: 0.95–1.22, P = 0.260]. Consistently, in time‐varying models, CCB treatment was not linked to long‐term mortality (HR: 0.97, 95% CI: 0.87–1.09, P = 0.682 and SHR: 1.05, 95% CI: 0.94–1.18, P = 0.359). This null association remained in subgroup analysis according to device strategy and propensity‐matching analyses. Neurological dysfunction, stroke, bleeding, rehospitalization, and renal dysfunction were more likely to occur among those with CCB when compared with those without CCB treatment. Conclusions In patients with LVAD, CCB therapy fails to show benefits in long‐term survival and is associated with increased incidences of neurological dysfunction, bleeding, renal dysfunction, and rehospitalization