Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.240
Filtrar
1.
Skelet Muscle ; 14(1): 21, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39354597

RESUMEN

BACKGROUND: Gene editing therapies in development for correcting out-of-frame DMD mutations in Duchenne muscular dystrophy aim to replicate benign spontaneous deletions. Deletion of 45-55 DMD exons (del45-55) was described in asymptomatic subjects, but recently serious skeletal and cardiac complications have been reported. Uncovering why a single mutation like del45-55 is able to induce diverse phenotypes and grades of severity may impact the strategies of emerging therapies. Cellular models are essential for this purpose, but their availability is compromised by scarce muscle biopsies. METHODS: We introduced, as a proof-of-concept, using CRISPR-Cas9 edition, a del45-55 mimicking the intronic breakpoints harboured by a subset of patients of this form of dystrophinopathy (designing specific gRNAs), into a Duchenne patient's cell line. The edited cell line was characterized evaluating the dystrophin expression and the myogenic status. RESULTS: Dystrophin expression was restored, and the myogenic defects were ameliorated in the edited myoblasts harbouring a specific del45-55. Besides confirming the potential of CRISPR-Cas9 to create tailored mutations (despite the low cleavage efficiency of our gRNAs) as a useful approach to generate in vitro models, we also generated an immortalized myoblast line derived from a patient with a specific del45-55. CONCLUSIONS: Overall, we provide helpful resources to deepen into unknown factors responsible for DMD-pathophysiology.


Asunto(s)
Sistemas CRISPR-Cas , Distrofina , Exones , Edición Génica , Terapia Genética , Distrofia Muscular de Duchenne , Humanos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Distrofina/genética , Edición Génica/métodos , Terapia Genética/métodos , Línea Celular , Eliminación de Secuencia , Mioblastos/metabolismo
2.
bioRxiv ; 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39282381

RESUMEN

Systems vaccinology studies have been used to build computational models that predict individual vaccine responses and identify the factors contributing to differences in outcome. Comparing such models is challenging due to variability in study designs. To address this, we established a community resource to compare models predicting B. pertussis booster responses and generate experimental data for the explicit purpose of model evaluation. We here describe our second computational prediction challenge using this resource, where we benchmarked 49 algorithms from 53 scientists. We found that the most successful models stood out in their handling of nonlinearities, reducing large feature sets to representative subsets, and advanced data preprocessing. In contrast, we found that models adopted from literature that were developed to predict vaccine antibody responses in other settings performed poorly, reinforcing the need for purpose-built models. Overall, this demonstrates the value of purpose-generated datasets for rigorous and open model evaluations to identify features that improve the reliability and applicability of computational models in vaccine response prediction.

3.
Ecol Evol ; 14(9): e70291, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39279788

RESUMEN

Understanding the movements and mortality of individuals across different life stages is crucial for the effective conservation of wild populations. We used data from 32 Egyptian vultures (Neophron percnopterus) tagged with GPS transmitters as nestlings in three Iberian breeding areas to study their dependence period, migration routes, movements in Africa, and mortality at each stage. Our results show no significant differences in the timing of nest departure or the duration of the dependence period between individuals of different sexes or breeding nuclei. Most juveniles migrated to sub-Saharan Africa in their first year, but some (3 of 32, 9.4%) remained in the Iberian Peninsula. Individuals that migrated to Africa did so annually, while those remaining in Iberia never migrated to the Sahel, indicating distinct migratory and non-migratory strategies. Non-migratory individuals consistently moved northward during the breeding season to their natal territories. Siblings did not coordinate their migration strategy or timing. All juveniles showed extensive overlap in the vast areas used in Africa, where females arrived before males, and in the Iberian Peninsula. Our study also revealed that no juveniles died immediately after fledging, but that none of the tagged individuals lived more than 7 years or were recruited as breeders. Although most casualties occurred during the longer stay in the Sahel, the mortality rate was highest during the few days of the first migration. Our results show that despite small variations in movement patterns between breeding nuclei and sexes, Egyptian vultures face similar challenges during the years before recruitment as breeders, mostly determined by their migratory strategy. These findings are relevant for designing conservation strategies, both in breeding areas and, more importantly, in wintering areas and along migration pathways. Such strategies will significantly impact the entire Iberian population of this endangered species.

4.
Sci Rep ; 14(1): 22550, 2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39343947

RESUMEN

Patterned polarizers are prepared using liquid crystals (LC) doped with a black dichroic dye and in combination with a linear polarizer. The pattern is achieved with a nanostructured LC alignment surface, that is generated using a two-photon polymerization direct laser write (2PP-DLW). This technique creates a pattern of high-resolution grooves in the photoresist at any arbitrary angle. The angle governs the LC orientation at any substrate surface point, determining the transmitted light linear polarization angle. This paper presents the first use of a 2PP-DLW cured positive tone photoresist for dichroic dye-doped LC alignment. Two complementary photoresists have been employed: conventional negative tone SU-8 photoresist and, in this context novel, positive tone S1805 photoresist. The alignment quality of the polarizers has been assessed by analyzing the transmission using an additional polarizer. For SU-8, the resulting grayscale pattern and a contrast ratio (CR) of 14 has measured. The uniformity of the alignment has been measured to be 65% using normalized Shannon entropy (H). For S1805, a CR of 37 was measured, and a uniformity of 63% was obtained. 2PP-DLW allows for shaping complex patterns in submicron dimensions and for the fabrication of arbitrarily patterned polarizers and other LC devices.

5.
Transl Anim Sci ; 8: txae131, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39346700

RESUMEN

This study aimed to evaluate the effects of a blend of different sources of magnesium oxide associated or not with monensin, on productive, ruminal, and nutritional parameters of steers. Eighty-four Nellore steers with an initial body weight (BW) of 367.3 ±â€…37.9 kg were allocated to one of 28 pens, with three steers per pen. Each pen was considered an experimental unit. Using a completely randomized design with a 2 × 2 factorial arrangement, the following treatments were assigned to each pen: 1) Control (CON)-a basal diet without additive inclusion; 2) Magnesium oxide blend (MG)-basal diet plus a magnesium-based product (pHix-up, Timab Magnesium, Dinard, France) provided at 0.50% of dry matter (DM); 3) Monensin (MON)-basal diet plus 25 mg/ kg of DM of sodium monensin (Rumensin, Elanco Animal Health, Greenfield, IN); and 4) MG association with MON-basal diet plus MG + MON, at the same doses of the individual treatments. The experimental period lasted 100 d. Blood samples were collected on days 0, 13, and 70 to determine d-lactate levels. Daily feed intake was recorded, and animal ingestive behavior was visually observed on days 66 and 67. On day 70, skeletal muscle tissue samples were obtained through biopsy for gene expression analysis. At the end of the experimental period, carcass ultrasonography was conducted. Subsequently, the steers were slaughtered, and rumen epithelium samples were collected for morphometric analysis. The use of monensin, of magnesium oxide blend, and their interactions, were treated as fixed effects, while the pens were considered as a random effect. Statistical differences were considered when P < 0.05. Steers-fed MG-containing diets consumed approximately 0.6 kg more DM per day than those fed diets without this additive (P = 0.01; 11.3 vs. 11.9 kg/d). The inclusion of MG in the diet increased (P = 0.02) the average daily gain. There was a greater Longissimus muscle area (LMA) and LMA per 100 kg of BW (P ≤ 0.03) for steers-fed diets with MG. Steers-fed MON exhibited reduced mRNA expression of the Atrogin-1 and mTOR compared to steers-fed MG + MON diets (MON × MG: P ≤ 0.04). Steers-fed MON had 6.9% greater feed efficiency (P = 0.02). Papillae width was lesser for CON than other treatments (MON × MG: P = 0.02). In conclusion, the magnesium oxide blend improved performance and carcass traits in high-energy feedlot diets, while monensin enhanced feed efficiency, suggesting potential for their use as alternatives or complements in beef cattle nutrition.

6.
ACS Appl Mater Interfaces ; 16(38): 50679-50689, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39268861

RESUMEN

Ferroionic materials combine ferroelectric properties and spontaneous polarization with ionic phenomena of fast charge recombination and electrodic functionalities. In this paper, we propose the concept of tunable polarization in CeO2-δ (ceria) thin (5 nm) films induced by built-in remnant polarization of a BaTiO3 (BTO) ferroelectric thin film interface, which is buried under the ceria layer. Upward and downward fixed polarizations at the BTO thin film (10 nm) are achieved by the lattice termination engineering of the SrO or TiO2 terminated Nb:SrTiO3 (NSTO or STN) substrate. We find that the ceria layer punctually replicates the polarization of the BTO interface via a dynamic reconfiguration of its intrinsic defects, i.e., oxygen vacancies and small polarons. Tunable oxidative or reducing properties (redox) also arise at the surface from the built-in polarization. Opposite polarities at the ceria termination tune the chemo-physical dynamics toward water molecule adsorbates. The inversion of the surface potential leads to a modulation of the water adsorption-desorption equilibrium and water ionization (splitting) redox overpotentials within ±400 mV at room temperature, depending on the ceria termination's charges. Such tunability opens up the perspectives of using ferroionics for wireless electrochemically enhanced catalysis.

7.
Bioresour Technol ; 413: 131529, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39321934

RESUMEN

Acclimating mesophilic biomass to low temperatures have been used to start-up psychrophilic anaerobic reactors, but limited microbial information is available during the acclimation. To investigate microbial responses to temperature reductions, duplicate lab-scale anaerobic digestion (AD) reactors were operated for 166 days, with the temperature being reduced from 37°C to 15°C, using synthetic long chain fatty acid (LCFA)-containing wastewater as the feedstock. The acclimated biomass at 15°C exhibited efficient removal of organic matter (total COD>75%, soluble COD>88%, and LCFA>99%). Temperature reductions lead to significant reductions in microbiome diversity. Fermentative bacteria were highly dynamic and functional redundant during temperature reductions. Smithella was the dominant syntrophic bacteria involved in LCFA degradation coupled with Methanothrix and Methanocorpusculum at 15°C. Membrane modifications and compatible cellular solutes production were triggered by temperature reductions as microbial response to cold stress. This study provided molecular insights in microbial acclimation to low temperatures for psychrophilic AD.

8.
J Clin Med ; 13(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39274496

RESUMEN

Background: Oral anticoagulation (OAC) is pivotal in the clinical management of atrial fibrillation (AF) patients. Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) prevent thromboembolic events, but information about the quality of life (QoL) and patient satisfaction in relation with the anticoagulant treatment is limited. Methods: REGUEIFA is a prospective, observational, and multicentre study that included patients with AF treated by cardiologists. We included patients treated with VKAs or DOACs. The EuroQol-5D (EQ-5D) questionnaire evaluated QoL, and the Anti-Clot Treatment Scale (ACTS) questionnaire investigated patient satisfaction with OAC. Results: A total of 904 patients were included (532 on VKA and 372 on DOACs). A total of 846 patients completed the EQ-5D questionnaire, with results significantly worse in patients on VKAs than on DOACs: more mobility limitations (37.6% vs. 24.2%, p < 0.001), more restriction in usual activities (24.7% vs. 18.3%, p = 0.026), more pain/discomfort (31.8% vs. 24.2%, p = 0.015), a lower visual analogue scale (VAS) score (66.4 ± 16.21 vs. 70.8 ± 15.6), and a lower EQ-D5 index (0.79 ± 0.21 vs. 0.85 ± 0.2, p < 0.001). After adjusting for baseline characteristics, VKA treatment was not an independent factor towards worse EQ-5D results. Also, 738 patients completed the ACTS questionnaire, and burden and profit scores were lower in patients on VKAs than for DOACs (52.1 ± 8.4 vs. 55.5 ± 6.8, p < 0.001 and 11.1 ± 2.4 vs. 11.8 ± 2.6, p < 0.001, respectively). The negative impact score was higher for VKAs than for DOACs (1.8 ± 1.02 vs. 1.6 ± 0.99, p < 0.001), with a general positive impact score lower for VKAs than for DOACs (3.6 ± 0.96 vs. 3.8 ± 1.02, p < 0.001). Conclusions: Patients on VKA have more comorbidity and worse EQ-5D and VAS scores than those on DOACs. VKA has a greater burden and higher negative impact on the patient's life than DOACs.

9.
Animals (Basel) ; 14(17)2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39272397

RESUMEN

The effect of including micronised fibre sources (FS) differing in fermentability and hydration capacity (HC) on growth performance, faecal digestibility, and caecal fermentation was investigated in piglets. There were four dietary treatments: a control diet (CON) and three treatments differing in the HC and fermentability of FS added at 1.5% to prestarter (28-42 d) and starter (42-61 d) diets. These were: LHC (low-HC by-product-based insoluble fibre (IF) with a prebiotic fraction (PF) from chicory root); MHC (medium-HC by-product-based IF with a PF); and HHC (high-HC non-fermentable wood-based IF with no PF). There were eight replicates per treatment. Over the entire period, LHC and MHC piglets showed a 10% increase in daily growth and feed intake (p ≤ 0.019) and tended to have a reduced feed conversion ratio (p = 0.087) compared to HHC piglets. At 42 d, faecal protein digestibility increased by 5% in the LHC and MHC groups compared with the HHC group (p = 0.035) and did not differ from the CON group. Both LHC and MHC fibres were more fermented in vitro with caecal inocula from 61 d old piglets than HHC fibre (p ≤ 0.003). These results suggest that balanced soluble and insoluble fibre concentrates can improve piglet performance.

10.
J Asthma Allergy ; 17: 879-887, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39309478

RESUMEN

Objective: To describe the clinical management of asthmatic patients and the level of compliance with the Guía Española para el Manejo del Asma (GEMA, Spanish Guidelines for Asthma Management) in the influential al area of Virgen de la Victoria University Hospital, Málaga (Spain). Materials and Methods: Descriptive, cross-sectional study in asthma patients from the Virgen de la Victoria University Hospital influential area, Málaga (Spain). Asthma Control Test (ACT) results, demographic and clinical characteristics, and GEMA indicators of quality asthma care were obtained from each participating patient. Results: Two hundred and eighty-eight patients (64.2% woman, mean age 48.6 years) were included in the study. The evaluation of the level of compliance with the GEMA quality indicators showed that in 20.8% of the patients the diagnosis of asthma was confirmed by spirometry and bronchodilator test, and 52.5% of the patients with suspicion of allergic asthma performed a sensitization test. Among the smoker patients, 76.3% were recommended to stop smoking; 14.2% of the patients received a paper-based educational plan. Regarding asthma treatment, 92.3% of patients with persistent asthma received inhaled glucocorticoids (IGC). IGC and LABA were the most common treatments for asthma, used in combination (ICG + LABA) in 139 (48.3%) patients; 32.6% discontinued SABA treatment during the study period. Asthma was well controlled in 54.9% of the patients (ACT score ≥20), and 13.9% of the patients registered exacerbations during the previous year with a mean (SD) of 1.38 (0.74) events. Conclusion: Most of the GEMA quality indicators of asthma care are not followed in real-world clinical practice. Specialists select the best option among the available treatments but there is an unmet need for training plans in other relevant aspects, such as diagnosis and/or disease monitoring.

11.
Res Sq ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39315258

RESUMEN

Identifying and refining clinically significant patient stratification is a critical step toward realizing the promise of precision medicine in asthma. Several peripheral blood hallmarks, including total peripheral blood eosinophil count (BEC) and immunoglobulin E (IgE) levels, are routinely used in asthma clinical practice for endotype classification and predicting response to state-of-the-art targeted biologic drugs. However, these biomarkers appear ineffective in predicting treatment outcomes in some patients, and they differ in distribution between racially and ethnically diverse populations, potentially compromising medical care and hindering health equity due to biases in drug eligibility. Here, we propose constructing an unbiased patient stratification score based on DNA methylation (DNAm) and utilizing it to refine the efficacy of hallmark biomarkers for predicting drug response. We developed Phenotype Aware Component Analysis (PACA), a novel contrastive machine-learning method for learning combinations of DNAm sites reflecting biomedically meaningful patient stratifications. Leveraging whole-blood DNAm from Latino (discovery; n=1,016) and African American (replication; n=756) pediatric asthma case-control cohorts, we applied PACA to refine the prediction of bronchodilator response (BDR) to the short-acting ß2-agonist albuterol, the most used drug to treat acute bronchospasm worldwide. While BEC and IgE correlate with BDR in the general patient population, our PACA-derived DNAm score renders these biomarkers predictive of drug response only in patients with high DNAm scores. BEC correlates with BDR in patients with upper-quartile DNAm scores (OR 1.12; 95% CI [1.04, 1.22]; P=7.9 e-4) but not in patients with lower-quartile scores (OR 1.05; 95% CI [0.95, 1.17]; P=0.21); and IgE correlates with BDR in above-median (OR for response 1.42; 95% CI [1.24, 1.63]; P=3.9e-7) but not in below-median patients (OR 1.05; 95% CI [0.92, 1.2]; P=0.57). These results hold within the commonly recognized type 2 (T2)-high asthma endotype but not in T2-low patients, suggesting that our DNAm score primarily represents an unknown variation of T2 asthma. Among T2-high patients with high DNAm scores, elevated BEC or IgE also corresponds to baseline clinical presentation that is known to benefit more from biologic treatment, including higher exacerbation scores, higher allergen sensitization, lower BMI, more recent oral corticosteroids prescription, and lower lung function. Our findings suggest that BEC and IgE, the traditional asthma biomarkers of T2-high asthma, are poor biomarkers for millions worldwide. Revisiting existing drug eligibility criteria relying on these biomarkers in asthma medical care may enhance precision and equity in treatment.

12.
Endocrinol Diabetes Nutr (Engl Ed) ; 71(7): 278-289, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39095283

RESUMEN

INTRODUCTION: All-cause mortality and cardiovascular mortality (CVM) risk can be very high in adults with type 2 diabetes mellitus (DM2) with previous cardiovascular disease (CVD). Our objective was to determine this risk among the different clinical spectrum of CVD. MATERIAL AND METHODS: The DIABET-IC trial is a multicenter, prospective, observational, and analytical study. Consecutive subjects with DM2 attending our outpatients' clinics were recruited. Data on clinical features, lab test results, and echocardiographic measures were collected. Patients were categorized depending on the presence and type of CVD: heart failure (HF), coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD). All-cause mortality and CVM were the dependent variables analyzed. Mortality rate was expressed as deaths per 1000 patients-year. Cox proportional hazards regressions models were used to establish the mortality risk associated with every type of CVD. RESULTS: We studied a total of 1246 patients (mean age, 6.3 (SD, 9.9) years; 31.6%, female) with an initial prevalence of CVD of 59.3%. A total of 122 deaths (46 due to CVD) occurred at the 2.6-year follow-up. All-cause and MCV rates associated with the presence of PAD (85.6/1000 and 33.6/1000, respectively) and HF (72.9/1000 and 28.7/1000 respectively) were the most elevated of all. In multivariate analysis, HF increased all-cause mortality risk (HR, 1.63; CI 95% 1.03-2.58; P=.037) and the risk of CVM (HR, 3.41; 95% CI, 1.68-6.93; P=.001). CONCLUSIONS: Mortality among DM2 patients is highly increased in the presence of HF and PAD. This justifies the screening of these conditions to intensify therapeutic strategies.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Masculino , Estudios Prospectivos , Enfermedades Cardiovasculares/mortalidad , Persona de Mediana Edad , Anciano , Causas de Muerte , Enfermedad Arterial Periférica/mortalidad , Angiopatías Diabéticas/mortalidad , Insuficiencia Cardíaca/mortalidad , Adulto
13.
Sensors (Basel) ; 24(15)2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39123816

RESUMEN

Gait monitoring using hip joint angles offers a promising approach for person identification, leveraging the capabilities of smartphone inertial measurement units (IMUs). This study investigates the use of smartphone IMUs to extract hip joint angles for distinguishing individuals based on their gait patterns. The data were collected from 10 healthy subjects (8 males, 2 females) walking on a treadmill at 4 km/h for 10 min. A sensor fusion technique that combined accelerometer, gyroscope, and magnetometer data was used to derive meaningful hip joint angles. We employed various machine learning algorithms within the WEKA environment to classify subjects based on their hip joint pattern and achieved a classification accuracy of 88.9%. Our findings demonstrate the feasibility of using hip joint angles for person identification, providing a baseline for future research in gait analysis for biometric applications. This work underscores the potential of smartphone-based gait analysis in personal identification systems.


Asunto(s)
Marcha , Articulación de la Cadera , Teléfono Inteligente , Humanos , Masculino , Femenino , Articulación de la Cadera/fisiología , Marcha/fisiología , Adulto , Acelerometría/instrumentación , Acelerometría/métodos , Algoritmos , Aprendizaje Automático , Análisis de la Marcha/métodos , Análisis de la Marcha/instrumentación , Caminata/fisiología , Adulto Joven
14.
ACS Appl Mater Interfaces ; 16(32): 42198-42209, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39091093

RESUMEN

Rare-earth doped CeO2 materials find extensive application in high-temperature energy conversion devices such as solid oxide fuel cells and electrolyzers. However, understanding the complex relationship between structural and electrical properties, particularly concerning rare-earth ionic size and content, remains a subject of ongoing debate, with conflicting published results. In this study, we have conducted comprehensive long-range and local order structural characterization of Ce1-xLnxO2-x/2 samples (x ≤ 0.6; Ln = La, Nd, Sm, Gd, and Yb) using X-ray and neutron powder diffraction, Raman spectroscopy, and electron diffraction. The increase in the rare-earth dopant content leads to a progressive phase transformation from a disordered fluorite structure to a C-type ordered superstructure, accompanied by reduced ionic conductivity. Samples with low dopant content (x = 0.2) exhibit higher ionic conductivity in Gd3+ and Sm3+ series due to lower lattice cell distortion. Conversely, highly doped samples (x = 0.6) exhibit superior conductivity for larger rare-earth dopant cations. Thermogravimetric analysis confirms increased water uptake and proton conductivity with increasing dopant concentration, while the electronic conductivity remains relatively unaffected, resulting in reduced ionic transport numbers. These findings offer insights into the relationship between transport properties and defect-induced local distortions in rare-earth doped CeO2, suggesting the potential for developing new functional materials with mixed ionic oxide, proton, and electronic conductivity for high-temperature energy systems.

15.
Small ; : e2404720, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39162223

RESUMEN

DNA nanostructures designed to interact with bilayer membranes are of fundamental interest as they mimic biological cytoskeletons and other membrane-associated proteins for applications in synthetic biology, biosensing, and biological research. Yet, there is limited insight into how the binary interactions are influenced by steric effects produced by 3D geometries of DNA structures and membranes. This work uses a 3D DNA nanostructure with membrane anchors in four different steric environments to elucidate the interaction with membrane vesicles of varying sizes and different local bilayer morphology. It is found that interactions are significantly affected by the steric environments of the anchors -often against predicted accessibility- as well as local nanoscale morphology of bilayers rather than on the usually considered global vesicle size. Furthermore, anchor-mediated bilayer interactions are co-controlled by weak contacts with non-lipidated DNA regions, as showcased by pioneering size discrimination between 50 and 200 nm vesicles. This study extends DNA nanotechnology to controlled bilayer interactions and can facilitate the design of nanodevices for vesicle-based diagnostics, biosensing, and protocells.

16.
J Neurosci ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39214705

RESUMEN

As evidence mounts that the cardiac-sympathetic nervous system reacts to challenging cognitive settings, we ask if these responses are epiphenomenal companions or if there is evidence suggesting a more intertwined role of this system with cognitive function. Healthy male and female human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous electroencephalographic (EEG) and cardiac-sympathetic signals. Participants were reward sensitive, but also experienced approach-avoidance "conflict" when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters suggested that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics were consistent with widening decision boundaries serving to combat reward-sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac "contractility" (an index of sympathetically mediated positive inotropy). We also saw evidence of conflict-specific "collaboration" between the neural and cardiac-sympathetic signals. In states of high conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signal's singular association. Cross-trial coherence analyses provided additional evidence that the autonomic systems controlling cardiac-sympathetics might influence the assessment of information streams during conflict by disrupting or overriding reward processing. We conclude that cardiac-sympathetic control might play a critical role, in collaboration with cognitive processes, during the approach-avoidance conflict in humans.Significance statement Complex behavior likely involves coordination across multiple branches of the human nervous system. We know much of how cortical systems of the brain adapt to cognitive challenges. In parallel, we are beginning to understand that autonomic mediated responses in peripheral organ (cardiac-sympathetic) systems might also play an adaptive role in cognition, particularly complex decisions. We probed if such signals have separate or collaborative associations with behavior, using computational models of decision behavior, brain (electroencephalography) and cardiac-sympathetic (contractility) data. Our evidence suggests that these systems might work together, as humans attend to all available information when resolving particularly conflicting decisions. The cardiac-sympathetic system may be part of a coordinated response that helps balance the human tendency to overly focus on rewards.

17.
Water Sci Technol ; 90(4): 1239-1249, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39215735

RESUMEN

The fast-growing global population has led to a substantial increase in food production, which generates large volumes of wastewater during the process. Despite most industrial wastewater being discharged at lower ambient temperatures (<20 °C), majority of the high-rate anaerobic reactors are operated at mesophilic temperatures (>30 °C). High-rate low-temperature anaerobic digestion (LtAD) has proven successful in treating industrial wastewater both at laboratory and pilot scales, boasting efficient organic removal and biogas production. In this study, we demonstrated the feasibility of two full-scale high-rate LtAD bioreactors treating meat processing and dairy wastewater, and the microbial communities in both reactors were examined. Both reactors exhibited rapid start-up, achieving considerable chemical oxygen demand (COD) removal efficiencies (total COD removal >80%) and generating high-quality biogas (CH4% in biogas >75%). Long-term operations (6-12 months) underscored the robustness of LtAD bioreactors even during winter periods (average temperature <12 °C), as evidenced by sustained high COD removal rates (total COD removal >80%). The stable performance was underpinned by a resilient microbial community comprising active acetoclastic methanogens, hydrolytic, and fermentative bacteria. These findings underscore the feasibility of high-rate low-temperature anaerobic wastewater treatment, offering promising solutions to the zero-emission wastewater treatment challenge.


Asunto(s)
Reactores Biológicos , Eliminación de Residuos Líquidos , Aguas Residuales , Anaerobiosis , Eliminación de Residuos Líquidos/métodos , Temperatura , Análisis de la Demanda Biológica de Oxígeno , Bacterias/metabolismo , Bacterias/clasificación , Biocombustibles , Residuos Industriales
18.
Microbiol Spectr ; : e0025424, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39194291

RESUMEN

Klebsiella pneumoniae is one of the most threatening multi-drug-resistant pathogens today, with phage therapy being a promising alternative for personalized treatments. However, the intrinsic capsule diversity in Klebsiella spp. poses a substantial barrier to the phage host range, complicating the development of broad-spectrum phage-based treatments. Here, we have isolated and genomically characterized phages capable of infecting each of the acquired 77 reference serotypes of Klebsiella spp., including capsular types widespread among high-risk K. pneumoniae clones causing nosocomial infections. We demonstrated the possibility of isolating phages for all capsular types in the collection, revealing high capsular specificity among taxonomically related phages, in contrast to a few phages that exhibited broad-spectrum infection capabilities. To decipher the determinants of the specificity of these phages, we focused on their receptor-binding proteins, with particular attention to depolymerases. We also explored the possibility of designing a broad-spectrum phage cocktail based on phages isolated in reference capsular-type strains and determining the ability to lyse relevant clinical isolates. A combination of 12 phages capable of infecting 55% of the reference Klebsiella spp. serotypes was tested on a panel of carbapenem-resistant K. pneumoniae clinical isolates. Thirty-one percent of isolates were susceptible to the phage cocktail. However, our results suggest that in a highly variable encapsulated bacterial host, phage hunting must be directed to the specific Klebsiella isolates. This work is a step forward in the understanding of the complexity of phage-host interactions and highlights the importance of implementing precise and phage-specific strategies to treat K. pneumoniae infections worldwide.IMPORTANCEThe emergence of resistant bacteria is a serious global health problem. In the absence of effective treatments, phages are a personalized and effective therapeutic alternative. However, little is still known about phage-host interactions, which are key to implementing effective strategies. Here, we focus on the study of Klebsiella pneumoniae, a highly pathogenic encapsulated bacterium. The complexity and variability of the capsule, where in most cases phage receptors are found, make it difficult for phage-based treatments. Here, we isolated a large collection of Klebsiella phages against all the reference strains and in a cohort of clinical isolates. Our results suggest that clinical isolates represent a challenge, especially high-risk clones. Thus, we propose targeted phage hunting as an effective strategy to implement phage-derived therapies. Our results are a step forward for new phage-based strategies to control K. pneumoniae infections, highlighting the importance of understanding phage-host interactions to design personalized treatments against Klebsiella spp.

19.
Front Oncol ; 14: 1398411, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39193388

RESUMEN

Background: Prostate cancer (PCa) is a leading cause of cancer-related deaths in European men, emphasizing the urgent need for effective risk assessment strategies. The TP53 gene, a tumor suppressor gene frequently mutated in cancer, commonly harbors the rs1042522 single nucleotide polymorphism (SNP), known as the P72R SNP, which may influence PCa susceptibility. This study investigated the prevalence of the P72R SNP in European Caucasian PCa samples and its association with PCa risk. Methods: Genotyping was conducted on 12 hormone-naïve aggressive PCa cultures (hnPCs) from untreated patients (Gleason ≥8), 11 radical prostatectomies (RP), and 94 serum samples using DNA Sanger sequencing and melting curve analysis. Comparative analysis utilized data from the GnomAD database's European Caucasian non-cancer population. Results: Our results demonstrate a significantly higher frequency of the P72R SNP in PCa samples and serums compared to the general European non-cancer population. A robust and statistically significant association (p < 0.0001) between the SNP and prostate cancer risk was identified, with an odds ratio of 7.937 (95% CI 5.37-11.00). Notably, the G allele (R72) showed a pronounced prevalence in high Gleason score (≥8) patients, although statistical significance was not reached. These results highlight a potential association with undifferentiated and malignant PCa lesions. Conclusion: The compelling association between the P72R SNP and prostate cancer risk underscores the potential utility of this marker for the early identification of patients at risk of aggressive metastatic prostate cancer. This insight could empower further research to intervene at an early stage by offering enhanced opportunities for timely and targeted interventions.

20.
Oral Oncol ; 157: 106971, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39067262

RESUMEN

BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon skin cancer that in more than 90 % of cases develops within the head and neck region. MCC is an aggressive disease with a dismal prognosis before the advent of immunotherapy. Avelumab, an anti-PDL1 agent is approved since 2017 for the treatment of advanced MCC after demonstrating a high response rate and favorable impact in survival. METHODS: Next generation sequencing (NGS) of the primary tumor biopsy from initial diagnosis (Foundation One CDx, Roche Diagnostics) as well as from plasma samples (Foundation One Liquid, Roche Diagnostics) obtained before and during treatment with avelumab were performed. RESULTS: We present the case of a patient with a metastatic MCC developing in the left parotid gland / pre-auricular area in an 80-year-old male with a long-lasting history of high UV exposure. After two cycles of avelumab 10 mg/kg/q2wk a near complete metabolic response and a major radiological response occurred in parallel to a brisk reduction in the ctDNA tumor fraction as well as variant-allele frequencies (VAFs) of all the mutations detected before the start of avelumab. CONCLUSION: Avelumab may achieve rapid and major responses in metastatic MCC. Our study demonstrates that ctDNA mirrors radiological responses and may serve as an ideal companion for diagnosis and disease monitoring in MCC.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma de Células de Merkel , ADN Tumoral Circulante , Neoplasias de Cabeza y Cuello , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/tratamiento farmacológico , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/farmacología , Anciano de 80 o más Años , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/genética , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA