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1.
NPJ Microgravity ; 10(1): 79, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060303

RESUMEN

Spaceflight presents significant challenges to the physiological state of living organisms. This can be due to the microgravity environment experienced during long-term space missions, resulting in alterations in muscle structure and function, such as atrophy. However, a comprehensive understanding of the adaptive mechanisms of biological systems is required to devise potential solutions and therapeutic approaches for adapting to spaceflight conditions. This review examines the current understanding of the challenges posed by spaceflight on physiological changes, alterations in metabolism, dysregulation of pathways and the suitability and advantages of using the model organism Caenorhabditis elegans nematodes to study the effects of spaceflight. Research has shown that changes in the gene and protein composition of nematodes significantly occur across various larval stages and rearing environments, including both microgravity and Earth gravity settings, often mirroring changes observed in astronauts. Additionally, the review explores significant insights into the fundamental metabolic changes associated with muscle atrophy and growth, which could lead to the development of diagnostic biomarkers and innovative techniques to prevent and counteract muscle atrophy. These insights not only advance our understanding of microgravity-induced muscle atrophy but also lay the groundwork for the development of targeted interventions to mitigate its effects in the future.

2.
J Med Chem ; 67(13): 10774-10782, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38900970

RESUMEN

Antibiotic resistance is an urgent threat to global health, with the decreasing efficacy of conventional drugs underscoring the urgency for innovative therapeutic strategies. Antimicrobial peptides present as promising alternatives to conventional antibiotics. Gramicidin S is one such naturally occurring antimicrobial peptide that is effective against Staphylococcus aureus, with a minimum inhibitory concentration (MIC) of 4 µg/mL (3.6 µM). Despite this potent activity, its significant hemolytic toxicity restricts its clinical use to topical applications. Herein, we present rational modifications to the key ß-strand and ß-turn regions of gramicidin S to concurrently mitigate hemolytic effects, while maintaining potency. Critically, peptide 9 displayed negligible hemolytic toxicity, while possessing significant antibacterial potency against a panel of methicillin-sensitive and methicillin-resistant S. aureus clinical isolates (MIC of 8 µg/mL, 7.2 µM). Given the substantial antibacterial activity and near absence of cytotoxicity, 9 presents as a potential candidate for systemic administration in the treatment of S. aureus bacteremia/sepsis.


Asunto(s)
Antibacterianos , Gramicidina , Hemólisis , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Hemólisis/efectos de los fármacos , Gramicidina/farmacología , Gramicidina/análogos & derivados , Humanos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Relación Estructura-Actividad , Eritrocitos/efectos de los fármacos , Animales
3.
J Am Soc Mass Spectrom ; 35(3): 613-621, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38393825

RESUMEN

Deoxyribonucleic acid is a genetic biomacromolecule that contains the inherited information required to build and maintain a living organism. While the canonical duplex DNA structure is rigorously characterized, the structure and function of higher order DNA structures such as DNA triplexes are comparatively poorly understood. Previous literature has shown that these triplexes can form under physiological conditions, and native mass spectrometry offers a useful platform to study their formation and stability. However, experimental conditions including buffer salt concentration, pH, and instrumentation parameters such as ion mode can confound analysis by impacting the amount of triplex observed by mass spectrometry. Using model 30mer Y-type triplex sequences, we demonstrate the influence a range of experimental variables have on the detection of DNA triplex structures, informing suitable conditions for the study. When carefully considered conditions are used, mass spectrometry offers a powerful complementary tool for the analysis of higher order DNA assemblies.


Asunto(s)
ADN , Conformación de Ácido Nucleico , ADN/química , Espectrometría de Masas
4.
PeerJ Comput Sci ; 10: e1733, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38259882

RESUMEN

Fraud detection through auditors' manual review of accounting and financial records has traditionally relied on human experience and intuition. However, replicating this task using technological tools has represented a challenge for information security researchers. Natural language processing techniques, such as topic modeling, have been explored to extract information and categorize large sets of documents. Topic modeling, such as latent Dirichlet allocation (LDA) or non-negative matrix factorization (NMF), has recently gained popularity for discovering thematic structures in text collections. However, unsupervised topic modeling may not always produce the best results for specific tasks, such as fraud detection. Therefore, in the present work, we propose to use semi-supervised topic modeling, which allows the incorporation of specific knowledge of the study domain through the use of keywords to learn latent topics related to fraud. By leveraging relevant keywords, our proposed approach aims to identify patterns related to the vertices of the fraud triangle theory, providing more consistent and interpretable results for fraud detection. The model's performance was evaluated by training with several datasets and testing it with another one that did not intervene in its training. The results showed efficient performance averages with a 7% increase in performance compared to a previous job. Overall, the study emphasizes the importance of deepening the analysis of fraud behaviors and proposing strategies to identify them proactively.

5.
PeerJ Comput Sci ; 9: e1676, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38077534

RESUMEN

Many studies have shown that air quality in cities is affected due to emissions of carbon from vehicles. As a result, policymakers (e.g., municipalities) intensely search for new ways to reduce air pollution due to its relation to health diseases. With this concern, connected vehicle technologies can leverage alternative on-road emissions control policies. The present investigation studies the impact on air pollution by (i) updating vehicles' routes to avoid pollution exposure (route choice policy), (ii) updating vehicles' speed limits (speed control policy), and (iii) considering electric vehicles (EVs). Vehicles are informed in advance about route conditions (i.e., on-road emissions) using the vehicular network. We found that by updating vehicle routes, 7.43% less CO emissions are produced within the evaluated region. Also, we find no evidence of significant emissions reductions in the case of limiting vehicles' speed. Lastly, with 30% of EV penetration, safe CO emissions levels are reached.

6.
Biotechnol Prog ; 36(4): e2980, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32067358

RESUMEN

Catechin compounds have potential benefits for recombinant monoclonal antibody (Mab) production as chemical additives in cell culture media. In this study, four catechin compounds catechin (Cat), epicatechin (EC), gallocatechin-gallate (GCG), and epigallocatechin-gallate (EGCG) were added to cell culture media (at 50 µM) and their effects on the recombinant Chinese hamster ovary (CHO) cell culture, specific productivity, and Mab quality were assessed. The results indicate that the improvement of specific productivity was linked to cell growth inhibition. All catechins caused cell phase growth arrest by lowering the number of cells in the G1/G0 phase and increasing the cells in the S and G2/M phases. Late addition of the catechin resulted in a significantly higher final IgG concentration. Cat and EC caused an improvement in the final antibody titer of 1.5 ± 0.1 and 1.3 ± 0.1 fold, respectively. Catechins with a galloyl group (GCG and EGCG) arrested cell growth and reduced cell specific productivity at the concentrations tested. The Cat-treated IgG was found to have reduced acidic species with a corresponding increase in the main peak.


Asunto(s)
Anticuerpos Monoclonales/biosíntesis , Catequina/análogos & derivados , Catequina/farmacología , Medios de Cultivo/farmacología , Animales , Anticuerpos Monoclonales/efectos de los fármacos , Células CHO/efectos de los fármacos , Catequina/química , Cricetulus , Medios de Cultivo/química
7.
Biotechnol Prog ; 36(3): e2940, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31742929

RESUMEN

The effect of the addition of resveratrol to cell culture media during the production of monoclonal antibodies was investigated. Treatments of Chinese hamster ovary (CHO) cells expressing immunoglobulin G (IgG) with 25 and 50 µM resveratrol showed that resveratrol was capable of slowing cell growth while almost doubling cell-specific productivity to 4.7 ± 0.6 pg IgG/cell·day, resulting in up to a 1.37-fold increase of the final IgG titer. A resveratrol concentration of 50 µM slowed the progression through the cell cycle temporarily by trapping cells in the S-phase. Cation exchange chromatography showed no significant difference in the composition of acidic or basic IgG species and size exclusion chromatography indicated no change in fragmentation or aggregation of the recombinant IgG in the treatment groups. Resveratrol could be used as a chemical additive to CHO media where it would enhance IgG productivity and provide a degree of protection against hydroxyl and superoxide free radicals, expanding the range of options for process improvement available to monoclonal antibody manufacturers.


Asunto(s)
Anticuerpos Monoclonales/biosíntesis , Proliferación Celular/efectos de los fármacos , Medios de Cultivo/farmacología , Resveratrol/farmacología , Animales , Anticuerpos Monoclonales/efectos de los fármacos , Células CHO , Cricetulus , Medios de Cultivo/química , Humanos , Resveratrol/química
8.
Artículo en Inglés | MEDLINE | ID: mdl-31652771

RESUMEN

A significant number of children suffer injuries from falls. The current measures of prevention and education regarding falls are not sufficient, as falling is still the main cause of injury at this age. This study aimed to evaluate the risk of injury during a backward fall and assess the effect of the Safe Fall training program on this risk. 457 primary school children between the ages of 6 and 12 (mean age of 9) were enrolled in a 6-week randomized intervention. The program was carried out during physical education classes and consisted of an intervention group that followed the Safe Fall training program and a control group that was given equilibrium exercises. The risk of injury was assessed before and after the implementation using the Information Scale on Safe Ways of Falling observation scale, evaluating the responses of five different body parts (head, hip, knees, upper limbs and back). Students' natural response to falls was associated with a high risk of injury in more than 90% of the cases. The implementation of the Safe Fall program resulted in a considerable decrease in this risk, with percentages lowered to levels between 8.7% and 18.3%.


Asunto(s)
Prevención de Accidentes/métodos , Accidentes por Caídas/prevención & control , Promoción de la Salud/métodos , Educación y Entrenamiento Físico/métodos , Heridas y Lesiones/prevención & control , Niño , Femenino , Humanos , Masculino , Destreza Motora , Evaluación de Resultado en la Atención de Salud , Método Simple Ciego , Heridas y Lesiones/etiología
9.
Antioxidants (Basel) ; 8(6)2019 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-31163664

RESUMEN

This study identified several antioxidants that could be used in Chinese hamster ovary (CHO)cell culture media and benefit monoclonal antibody production. The flavan-3-ols, catechin, epicatechin, epigallocatechin gallate and gallocatechin gallate all had no detrimental effect on cell viability at the concentrations tested, and they reduced the final viable cell count with a resulting rise in the cell specific productivity. The flavone, luteolin behave similarly to the flavan-3-ols. Resveratrol at 50 µM concentration resulted in the most pronounced reduction in viable cell density with minimal decrease in IgG synthesis and the largest increase in cell specific productivity. Low concentrations of α-tocopherol (35 µM) reduced viable cell density and raised cell specific productivity, but at higher concentration it had little additional effect. As high concentrations of α-tocopherol are not toxic to CHO cells, its addition as an anti-oxidant has great potential. Kaempferol up to 50 µM, curcumin up to 20 µM and piceid up to 100 µM showed little effect on growth or IgG synthesis and could be useful as antioxidants. Caffeic acid phenethyl ester was toxic to CHO cell and of no interest. Seven of the phenolic compounds tested are potential cell cycle inhibitors as well as having intrinsic antioxidant properties.

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