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1.
mBio ; : e0226424, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39283084

RESUMEN

Sexual reproduction in fungi allows genetic recombination and increases genetic diversity, allowing adaptation and survival. The velvet complex is a fungal-specific protein assembly that regulates development, pathogenesis, and secondary metabolism in response to environmental cues, such as light. In Neurospora crassa, this complex comprises VE-1, VE-2, and LAE-1. Deletion of ve-1 or ve-2, but not lae-1, leads to increased conidiation (asexual spore formation) and reduced sexual development. Mutants lacking ve-1 and/or ve-2 are female sterile and male fertile, indicating that a VE-1/VE-2 complex regulates the development of female structures. During sexual development, we observed differential regulation of 2,117 genes in dark and 4,364 genes in light between the wild type and the ∆ve-1 strain. The pheromone response and cell wall integrity pathways were downregulated in the ∆ve-1 mutant, especially in light. Additionally, we found reduced levels of both total and phosphorylated MAK-1 and MAK-2 kinases. In vitro experiments demonstrated the binding of VE-1 and VE-2 to the promoters of mak-1 and mak-2, suggesting a direct regulatory role of VE-1/VE-2 in the transcriptional control of MAPK genes to regulate sexual development. Deletion of the photosensor gene white-collar 1 prevented the light-dependent inhibition of sexual development in the ∆ve-1 mutant by increasing transcription of the pheromone response and cell wall integrity pathway genes to the levels in the dark. Our results support the proposal that the regulation of the MAP kinase pathways by the VE-1/VE-2 complex is a key element in transcriptional regulation that occurs during sexual development. IMPORTANCE: Sexual reproduction generates new gene combinations and novel phenotypic traits and facilitates evolution. Induction of sexual development in fungi is often regulated by environmental conditions, such as the presence of light and nutrients. The velvet protein complex coordinates internal cues and environmental signals to regulate development. We have found that VE-1, a component of the velvet complex, regulates transcription during sexual development in the fungus Neurospora crassa. VE-1 regulates the transcription of many genes, including those involved in mitogen-activated protein kinase (MAPK) signaling pathways that are essential in the regulation of sexual development, and regulates the activity of the MAPK pathway. Our findings provide valuable insights into how fungi respond to environmental signals and integrate them into their reproductive processes.

2.
Data Brief ; 56: 110857, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39281012

RESUMEN

This dataset results from controlled experiments that assess the tolerance of Urochloa spp. and Megathyrsus maximus grasses to nymphal and adult spittlebug damage, particularly from Aeneolamia varia, which significantly impacts forage production in Neotropical regions. Data were collected under standardized conditions using high-throughput phenotyping methods, integrating image-capture techniques and analyses to ensure precise and consistent data acquisition. The dataset serves as a foundational resource for developing and validating computer vision models aimed at automated phenotyping, enabling accurate and high-throughput assessment of plant tolerance to spittlebug damage. Researchers can use the dataset to benchmark and compare different methodologies for plant damage assessment, fostering standardization and reproducibility in phenotyping studies.

3.
J Extracell Biol ; 3(9): e170, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39290459

RESUMEN

Background: Current definition of chronic kidney disease (CKD) identifies only advanced stages, but effective management demands early detection. Urinary albumin-to-creatinine ratio (ACR) 30 mg/g is a cut-off point for CKD clinical diagnosis. Patients with lower values (normoalbuminuria) and eGFR > 60 mL/min/1.73 m2 are considered at no increased cardiorenal risk. However, higher incidence of renal function decline and cardiovascular events have been shown within the normoalbuminuria range. Novel subclinical indicators may help to identify higher-risk patients. Urinary extracellular vesicles (uEVs) are sentinels of renal function non-invasively. Here we aimed to approach the early assessment of cardiorenal risk by investigating the protein cargo of uEVs. Methods: Hypertensive patients were classified in control group (C) with ACR < 10 mg/g, and high-normal group (HN) with ACR 10-30 mg/g. Isolated uEVs were characterized by western blotting and electron microscopy and the protein cargo was analyzed by untargeted proteomics (LC-MS/MS) in a first discovery cohort. Protein confirmation was performed in a different cohort by ExoView. Immunohistochemistry of human kidney biopsies was also performed to evaluate the potential of uEVs to reflect renal damage. Results: HN albuminuria does not affect the uEVs concentration, size, or tetraspanin profile. Among >6200 uEVs proteins identified, 43 define a panel significantly altered in HN patients without variation in urine, mostly annotated in the tubule (39 out of 43). The tubular transporter long-chain fatty acid transport protein 2 (SLC27A2) and the apical membrane protein amnionless (AMN) confirmed their alteration in HN patients evidencing impaired tubular reabsorption. SLC27A2 showed tubular expression and significantly reduced levels in patients with diagnostic criteria for CKD. Conclusions: Alterations in the EV-mediated molecular profile are evident before pathological ACR levels are reached. Direct quantitation of SLC27A2 and AMN in uEVs helps identifying normoalbuminuric subjects with higher cardiorenal risk in early monitoring of CKD.

5.
Heliyon ; 10(16): e36284, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39262974

RESUMEN

The relevance of atmospheric particulate matter (PM) to health and the environment is widely known. Long-term studies are necessary for understanding current and future trends in air quality management. This study aimed to assess the long-term PM concentration in the Magdalena department (Colombia). It focused on the following aspects: i) spatiotemporal patterns, ii) correlation with meteorology, iii) compliance with standards, iv) temporal trends over time, v) impact on health, and vi) impact of policy management. Fifteen stations from 2003 to 2021 were analyzed. Spearman-Rho and Mann-Kendall methods were used to correlate concentration with meteorology. The temporal and five-year moving trends were determined, and the trend magnitude was calculated using Teil-Sen. Acute respiratory infection odd ratios and risk of cancer associated with PM concentration were used to assess the impact on health. The study found that the maximum PM10 concentration was 194.5 µg/m3, and the minimum was 3 µg/m3. In all stations, a negative correlation was observed between PM10 and atmospheric water content, while the wind speed and temperature showed a positive correlation. The global trends indicated an increasing value, with five fluctuations in five-year moving trends, consistent with PM sources and socio-economic behavior. PM concentrations were found to comply with national standard; however, the results showed a potential impact on population health. The management regulation had a limited impact on increasing concentration. Considering that national regulations tend to converge towards WHO standards, the study area must create a management program to ensure compliance.

6.
J Neurosurg Spine ; : 1-7, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39270317

RESUMEN

OBJECTIVE: The aim of this study was to compare the rate of achievement of the minimal clinically important difference (MCID) in patient-reported outcomes (PROs) and satisfaction between cervical spondylotic myelopathy (CSM) patients with and without class III obesity who underwent surgery. METHODS: The authors analyzed patients from the 14 highest-enrolling sites in the prospective Quality Outcomes Database CSM cohort. Patients were dichotomized based on whether or not they were obese (class III, BMI ≥ 35 kg/m2). PROs including visual analog scale (VAS) neck and arm pain, Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA), EQ-5D, and North American Spine Society patient satisfaction scores were collected at baseline and 24 months after cervical spine surgery. RESULTS: Of the 1141 patients with CSM who underwent surgery, 230 (20.2%) were obese and 911 (79.8%) were not. The 24-month follow-up rate was 87.4% for PROs. Patients who were obese were younger (58.1 ± 12.1 years vs 61.2 ± 11.6 years, p = 0.001), more frequently female (57.4% vs 44.9%, p = 0.001), and African American (22.6% vs 13.4%, p = 0.002) and had a lower education level (high school or less: 49.1% vs 40.8%, p = 0.002) and a higher American Society of Anesthesiologists grade (2.7 ± 0.5 vs 2.5 ± 0.6, p < 0.001). Clinically at baseline, the obese group had worse neck pain (VAS score: 5.7 ± 3.2 vs 5.1 ± 3.3), arm pain (VAS score: 5.4 ± 3.5 vs 4.8 ± 3.5), disability (NDI score: 42.7 ± 20.4 vs 37.4 ± 20.7), quality of life (EQ-5D score: 0.54 ± 0.22 vs 0.56 ± 0.22), and function (mJOA score: 11.6 ± 2.8 vs 12.2 ± 2.8) (all p < 0.05). At the 24-month follow-up, however, there was no difference in the change in PROs between the two groups. Even after accounting for relevant covariates, no significant difference in achievement of MCID and satisfaction was observed between the two groups at 24 months. CONCLUSIONS: Despite the class III obese group having worse baseline clinical presentations, the two cohorts achieved similar rates of satisfaction and MCID in PROs. Class III obesity should not preclude and/or delay surgical management for patients who would otherwise benefit from surgery for CSM.

7.
Nat Commun ; 15(1): 7114, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237504

RESUMEN

Culturing and genomic sequencing of Mycobacterium tuberculosis (MTB) from tuberculosis (TB) cases is the basis for many research and clinical applications. The alternative, culture-free sequencing from diagnostic samples, is promising but poses challenges to obtain and analyse the MTB genome. Paradoxically, culture is assumed to impose a diversity bottleneck, which, if true, would entail unexplored consequences. To unravel this paradox we generate high-quality genomes of sputum-culture pairs from two different settings after developing a workflow for sequencing from sputum and a tailored bioinformatics analysis. Careful downstream comparisons reveal sources of sputum-culture incongruences due to false positive/negative variation associated with factors like low input MTB DNA or variable genomic depths. After accounting for these factors, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants' frequency (0.98). The combined analysis from five different settings and more than 100 available samples shows that our results can be extrapolated to different TB epidemic scenarios, demonstrating that for the cases tested culture accurately mirrors clinical samples.


Asunto(s)
Variación Genética , Mycobacterium tuberculosis , Esputo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Esputo/microbiología , Humanos , Tuberculosis/microbiología , Tuberculosis/diagnóstico , Genoma Bacteriano , ADN Bacteriano/genética , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/diagnóstico
8.
Mater Today Bio ; 28: 101187, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39221198

RESUMEN

Silica-based scaffolds are promising in Tissue Engineering by enabling personalized scaffolds, boosting exceptional bioactivity and osteogenic characteristics. Moreover, silica materials are highly tunable, allowing for controlled drug release to enhance tissue regeneration. In this study, we developed a 3D printable silica material with controlled mesoporosity, achieved through the sol-gel reaction of tetraethyl orthosilicate (TEOS) at mild temperatures with the addition of different calcium concentrations. The resultant silica inks exhibited high printability and shape fidelity, while maintaining bioactivity and biocompatibility. Notably, the increased mesopore size enhanced the incorporation and release of large molecules, using cytochrome C as a drug model. Due to the varying surface charge of silica depending on the pH, a pH-dependent control release was obtained between pH 2.5 and 7.5, with maximum release in acidic conditions. Therefore, silica with controlled mesoporosity could be 3D printed, acting as a pH stimuli responsive platform with therapeutic potential.

9.
ESC Heart Fail ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39226189

RESUMEN

AIMS: Left ventricular hypertrophy (LVH) has been associated with an increased risk of cardiovascular (CV) disease and linked to increased morbidity and mortality. In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), hypertension is common, and patients with these co-morbidities additionally have a high prevalence of LVH. This analysis of the prespecified pooled FIDELITY analysis comprising the randomized, double-blind, placebo-controlled, multicentre FIDELIO-DKD and FIGARO-DKD phase III studies aimed to explore the CV and kidney effects of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in patients with CKD and T2D stratified by a diagnosis of LVH at baseline. METHODS AND RESULTS: A diagnosis of LVH in the FIDELITY patient population was determined at baseline using investigator-reported electrocardiogram (ECG) findings. The two efficacy outcomes, assessed by baseline LVH, were the composite CV outcome of time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure (HHF), and a composite kidney outcome of time to onset of kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) ≥57% from baseline over ≥4 weeks, or kidney-related death. Safety outcomes by baseline LVH were reported as treatment-emergent adverse events. At baseline out of 13 026 patients in FIDELITY, 96.5% had hypertension and 9.6% had investigator-reported LVH. The relative risk reduction for the composite CV and kidney outcomes with finerenone versus placebo was lower in the LVH subgroup; however, the treatment effect of finerenone was not modified by baseline LVH for either outcome (Pinteraction = 0.1075 for composite CV outcome and Pinteraction = 0.1782 for composite kidney outcome). Analysis of the composite CV outcome components showed a greater reduction in the risk of HHF versus placebo for patients with baseline LVH compared with those without (Pinteraction = 0.0024). Overall safety events were comparable between the LVH subgroups and treatment arms. Treatment-emergent hyperkalaemia was observed more frequently with finerenone versus placebo, but discontinuation rates were low in both treatment arms and between LVH subgroups. CONCLUSIONS: In conclusion, the overall CV and kidney benefits of finerenone versus placebo were not modified by the presence of LVH at baseline, with overall safety findings being similar between LVH subgroups. A greater benefit was observed for HHF in patients with versus without LVH, suggesting that LVH may be a predictor of the treatment effect of finerenone on HHF.

10.
Hypertension ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39247961

RESUMEN

BACKGROUND: Resistant hypertension is characterized by elevated blood pressure (BP) despite using 3 antihypertensive agents. Ambulatory BP monitoring (ABPM) detects the presence of white-coat resistant hypertension (24-hour BP <130/80 mm Hg). The aim of the study was to evaluate risks of death in resistant hypertension compared with controlled hypertension, as well as in ABPM-confirmed (24-hour BP ≥130 or 80 mm Hg), versus white-coat resistant hypertension. METHODS: We selected 8146 patients with controlled hypertension (office BP <140/90 mm Hg while being treated with ≤3 antihypertensive drugs) and 8577 with resistant hypertension (BP ≥140 or ≥90 mm Hg while being treated with ≥3 drugs). All-cause and cardiovascular mortalities (median follow-up, 9.7 years) were compared between groups, as well as between patients with white-coat (3289) and ABPM-confirmed (5288) resistant hypertension. Hazard ratios (HRs) from Cox models after adjustment for clinical confounders were used for comparisons. RESULTS: Compared with controlled hypertension, resistant hypertension was associated with an increased risk in all-cause (HR, 1.21 [95% CI, 1.12-1.30]) and cardiovascular mortalities (HR, 1.33 [95% CI, 1.17-1.51]) in confounder-adjusted models. Compared with white-coat, ABPM-confirmed resistant hypertension was associated with an increased risk of all-cause (HR, 1.45 [95% CI, 1.32-1.60]) and cardiovascular (HR, 1.68 [95% CI, 1.43-1.98]) mortalities. When ABPM-confirmed and white-coat resistant hypertension were separately compared with controlled hypertension, only the former was associated with an increased risk of death and cardiovascular death (HR, 1.36 [95% CI, 1.26-1.48] and 1.56 [95% CI, 1.36-1.79]), respectively. CONCLUSIONS: ABPM-confirmed resistant hypertension is associated with an increased risk of death and cardiovascular death with respect to both controlled hypertension and white-coat resistant hypertension.

11.
J Neurosurg Spine ; : 1-12, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39241256

RESUMEN

OBJECTIVE: Myelopathy in the cervical spine can present with diverse symptoms, many of which can be debilitating for patients. Patients with radiculopathy symptoms demonstrate added complexity because of the overlapping symptoms and treatment considerations. The authors sought to assess outcomes in patients with myelopathy presenting with or without concurrent radiculopathy. METHODS: The Quality Outcomes Database, a prospectively collected multi-institutional database, was used to analyze demographic, clinical, and surgical variables of patients presenting with myelopathy or myeloradiculopathy as a result of degenerative pathology. Outcome measures included arm (VAS-arm) and neck (VAS-neck) visual analog scale (VAS) scores, modified Japanese Orthopaedic Association (mJOA) scale score, EuroQol VAS (EQ-VAS) score, and Neck Disability Index (NDI) at 3, 12, and 24 months compared with baseline. RESULTS: A total of 1015 patients were included in the study: 289 patients with myelopathy alone (M0), 239 with myeloradiculopathy but no arm pain (MRAP-), and 487 patients with myeloradiculopathy and arm pain (MRAP+). M0 patients were older than the myeloradiculopathy cohorts combined (M0 64.2 vs MRAP- + MRAP+ 59.5 years, p < 0.001), whereas MRAP+ patients had higher BMI and a greater incidence of current smoking compared with the other cohorts. There were more anterior approaches used in in MRAP+ patients and more posterior approaches used in M0 patients. In severely myelopathic patients (mJOA scale score ≤ 10), posterior approaches were used more often for M0 (p < 0.0001) and MRAP+ (p < 0.0001) patients. Patients with myelopathy and myeloradiculopathy both exhibited significant improvement at 1 and 2 years across all outcome domains. The amount of improvement did not vary based on surgical approach. In comparing cohort outcomes, postoperative outcome differences were associated with patient-reported scores at baseline. CONCLUSIONS: Patients with myelopathy and those with myeloradiculopathy demonstrated significant and similar improvement in arm and neck pain scores, myelopathy, disability, and quality of life at 3 months that was sustained at 1- and 2-year follow-up intervals. More radicular symptoms and arm pain increased the likelihood of a surgeon choosing an anterior approach, whereas more severe myelopathy increased the likelihood of approaching posteriorly. Surgical approach itself was not an independent predictor of outcome.

12.
Nat Med ; 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39218030

RESUMEN

Cardiovascular-kidney-metabolic syndrome is an emerging entity that connects cardiovascular diseases, chronic kidney disease, and diabetes. The non-steroidal mineralocorticoid receptor antagonist, finerenone, has been studied in three prospective randomized clinical trials of patients with cardio-kidney-metabolic syndrome: FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF. In light of the strong epidemiological overlap and shared mechanistic drivers of clinical outcomes across cardio-kidney-metabolic syndrome, we summarize the efficacy and safety of finerenone on cardiovascular, kidney, and mortality outcomes in this prespecified participant-level pooled analysis. The three trials included 18,991 participants (mean age 67 ± 10 years; 35% women). During 2.9 years median follow-up, the primary outcome of cardiovascular death occurred in 421 (4.4%) assigned to finerenone and 471 (5.0%) assigned to placebo (HR 0.89; 95% CI 0.78-1.01; P = 0.076). Death from any cause occurred in 1,042 (11.0%) participants in the finerenone arm and 1,136 (12.0%) in the placebo arm (HR 0.91; 95% CI 0.84-0.99; P = 0.027). Finerenone further reduced the risk of HF hospitalization (HR 0.83; 95% CI 0.75-0.92; P < 0.001) and the composite kidney outcome (HR 0.80; 95% CI 0.72-0.90; P < 0.001). While this pooled analysis failed to demonstrate significant reductions in cardiovascular death, finerenone was associated with significantly lower deaths of any cause, cardiovascular events, and kidney outcomes. PROSPERO identifier: CRD42024570467.

13.
Angew Chem Int Ed Engl ; : e202411861, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110601

RESUMEN

Starphenes are structurally appealing three-fold symmetric polycyclic aromatic compounds with potential interesting applications in molecular electronics and nanotechnology. This family of star-shaped polyarenes can be regarded as three acenes that are connected through a single benzene ring. In fact, just like acenes, unsubstituted large starphenes are poorly soluble and highly reactive molecules under ambient conditions making their synthesis difficult to achieve. Herein, we report two different synthetic strategies to obtain a starphene formed by 19 cata-fused benzene rings distributed within three hexacene branches. This molecule, which is the largest starphene that has been obtained to date, was prepared by combining solution-phase and on-surface synthesis. [19]Starphene was characterized by high-resolution scanning tunneling microscopy (STM) and spectroscopy (STS) showing a remarkable small HOMO-LUMO transport gap (0.9 eV).

14.
J Med Syst ; 48(1): 77, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39172169

RESUMEN

Increased patient access to electronic medical records and resources has resulted in higher volumes of health-related questions posed to clinical staff, while physicians' rising clinical workloads have resulted in less time for comprehensive, thoughtful responses to patient questions. Artificial intelligence chatbots powered by large language models (LLMs) such as ChatGPT could help anesthesiologists efficiently respond to electronic patient inquiries, but their ability to do so is unclear. A cross-sectional exploratory survey-based study comprised of 100 anesthesia-related patient question/response sets based on two fictitious simple clinical scenarios was performed. Each question was answered by an independent board-certified anesthesiologist and ChatGPT (GPT-3.5 model, August 3, 2023 version). The responses were randomized and evaluated via survey by three blinded board-certified anesthesiologists for various quality and empathy measures. On a 5-point Likert scale, ChatGPT received similar overall quality ratings (4.2 vs. 4.1, p = .81) and significantly higher overall empathy ratings (3.7 vs. 3.4, p < .01) compared to the anesthesiologist. ChatGPT underperformed the anesthesiologist regarding rate of responses in agreement with scientific consensus (96.6% vs. 99.3%, p = .02) and possibility of harm (4.7% vs. 1.7%, p = .04), but performed similarly in other measures (percentage of responses with inappropriate/incorrect information (5.7% vs. 2.7%, p = .07) and missing information (10.0% vs. 7.0%, p = .19)). In conclusion, LLMs show great potential in healthcare, but additional improvement is needed to decrease the risk of patient harm and reduce the need for close physician oversight. Further research with more complex clinical scenarios, clinicians, and live patients is necessary to validate their role in healthcare.


Asunto(s)
Anestesiólogos , Humanos , Estudios Transversales , Registros Electrónicos de Salud/normas , Inteligencia Artificial , Empatía , Encuestas y Cuestionarios , Femenino , Masculino , Anestesiología/normas
15.
Environ Int ; 190: 108907, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39121825

RESUMEN

Environmental exposures and gene-exposure interactions are the major causes of some diseases. Early-life exposome studies are needed to elucidate the role of environmental exposures and their complex interactions with biological mechanisms involved in childhood health. This study aimed to determine the contribution of early-life exposome to DNA damage and the modifying effect of genetic polymorphisms involved in air pollutants metabolism, antioxidant defense, and DNA repair. We conducted a cohort study in 416 Colombian children under five years. Blood samples at baseline were collected to measure DNA damage by the Comet assay and to determine GSTT1, GSTM1, CYP1A1, H2AX, OGG1, and SOD2 genetic polymorphisms. The exposome was estimated using geographic information systems, remote sensing, LUR models, and questionnaires. The association exposome-DNA damage was estimated using the Elastic Net linear regression with log link. Our results suggest that exposure to PM2.5 one year before the blood draw (BBD) (0.83, 95 %CI: 0.76; 0.91), soft drinks consumption (0.94, 0.89; 0.98), and GSTM1 null genotype (0.05, 0.01; 0.36) diminished the DNA damage, whereas exposure to PM2.5 one-week BBD (1.18, 1.06; 1.32), NO2 lag-5 days BBD (1.27, 1.18; 1.36), in-house cockroaches (1.10, 1.00; 1.21) at the recruitment, crowding at home (1.34, 1.08; 1.67) at the recruitment, cereal consumption (1.11, 1.04; 1.19) and H2AX (AG/GG vs. AA) (1.44, 1.11; 1.88) increased the DNA damage. The interactions between H2AX (AG/GG vs. AA) genotypes with crowding and PM2.5 one week BBD, GSTM1 (null vs. present) with humidity at the first year of life, and OGG1 (SC/CC vs. SS) with walkability at the first year of life were significant. The early-life exposome contributes to elucidating the effect of environmental exposures on DNA damage in Colombian children under five years old. The exposome-DNA damage effect appears to be modulated by genetic variants in DNA repair and antioxidant defense enzymes.


Asunto(s)
Contaminantes Atmosféricos , Daño del ADN , Exposición a Riesgos Ambientales , Interacción Gen-Ambiente , Humanos , Preescolar , Colombia , Masculino , Femenino , Lactante , Exposoma , Estudios de Cohortes , Glutatión Transferasa/genética , Material Particulado , Polimorfismo Genético , Contaminación del Aire/efectos adversos , Contaminación del Aire/estadística & datos numéricos
17.
bioRxiv ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39149259

RESUMEN

Microglia, the innate immune cells in the central nervous system, exhibit distinct transcriptional profiles across brain regions that are important for facilitating their specialized function. There has been recent interest in identifying the epigenetic modifications associated with these distinct transcriptional profiles, as these may improve our understanding of the underlying mechanisms governing the functional specialization of microglia. One obstacle to achieving this goal is the large number of microglia required to obtain a genome-wide profile for a single histone modification. Given the cellular and regional heterogeneity of the brain, this would require pooling many samples which would impede biological applications that are limited by numbers of available animals. To overcome this obstacle, we have adapted a method of chromatin profiling known as Cleavage Under Targets and Tagmentation (CUT&Tag-Direct) to profile histone modifications associated with regional differences in gene expression throughout the brain reward system. Consistent with previous studies, we find that transcriptional profiles of microglia vary by brain region. However, here we report that these regional differences also exhibit transcriptional network signatures specific to each region. Additionally, we find that these region-dependent network signatures are associated with differential deposition of H3K27ac and H3K7me3, and while the H3K27me3 landscape is remarkably stable across brain regions, the H3K27ac landscape is most consistent with the anatomical location of microglia which explain their distinct transcriptional profiles. Altogether, these findings underscore the established role of H3K27me3 in cell fate determination and support the active role of H3K27ac in the dynamic regulation of microglial gene expression. In this study, we report a molecular and computational framework that can be applied to improve our understanding of the role of epigenetic regulation in microglia in both health and disease, using as few as 2,500 cells per histone mark.

18.
Adv Drug Deliv Rev ; 212: 115420, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39096937

RESUMEN

The evaluation of the diffusion properties of different molecules in tissues is a subject of great interest in various fields, such as dermatology/cosmetology, clinical medicine, implantology and food preservation. In this review, a discussion of recent studies that used kinetic spectroscopy measurements to evaluate such diffusion properties in various tissues is made. By immersing ex vivo tissues in agents or by topical application of those agents in vivo, their diffusion properties can be evaluated by kinetic collimated transmittance or diffuse reflectance spectroscopy. Using this method, recent studies were able to discriminate the diffusion properties of agents between healthy and diseased tissues, especially in the cases of cancer and diabetes mellitus. In the case of cancer, it was also possible to evaluate an increase of 5% in the mobile water content from the healthy to the cancerous colorectal and kidney tissues. Considering the application of some agents to living organisms or food products to protect them from deterioration during low temperature preservation (cryopreservation), and knowing that such agent inclusion may be reversed, some studies in these fields are also discussed. Considering the broadband application of the optical spectroscopy evaluation of the diffusion properties of agents in tissues and the physiological diagnostic data that such method can acquire, further studies concerning the optimization of fruit sweetness or evaluation of poison diffusion in tissues or antidote application for treatment optimization purposes are indicated as future perspectives.


Asunto(s)
Neoplasias , Humanos , Difusión , Animales , Neoplasias/metabolismo , Luz , Análisis Espectral/métodos , Diabetes Mellitus/metabolismo
19.
Anal Methods ; 16(33): 5652-5664, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39109659

RESUMEN

The intricate composition of microalgal pigments plays a crucial role in various biological processes, from photosynthesis to biomarker identification. Traditional pigment analysis methods involve complex extraction techniques, posing challenges in maintaining analyte integrity. In this study, we employ Electron Transfer Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (ET-MALDI-MS) to compare the pigmentary profiles of Chlorella vulgaris intact cells, chloroplasts, and solvent extracts. We aim to obtain comprehensive extracts rich in polar and non-polar compounds using ultrasound-assisted and supercritical fluid extraction methods. Additionally, intact chloroplasts are isolated using a lysis buffer and sucrose density gradient centrifugation. Our ET-MALDI-MS analysis reveals distinct compositional differences, highlighting the impact of extraction protocols on microalgal pigment identification. We observe prominent signals corresponding to radical cations of key pigments, including chlorophylls and carotenoids, which are crucial for C. vulgaris identification. Furthermore, ET-MALDI-MS facilitates the identification of specific lipids within chloroplast membranes and other organelles. This study underscores the rapid and precise nature of ET-MALDI-MS in microalgal biomarker analysis, providing valuable insights into phytoplankton dynamics, trophic levels, and environmental processes. C. vulgaris emerges as a promising model for studying pigment composition and membrane lipid diversity, enhancing our understanding of microalgal ecosystems.


Asunto(s)
Chlorella vulgaris , Cloroplastos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Chlorella vulgaris/química , Chlorella vulgaris/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Cloroplastos/química , Cloroplastos/metabolismo , Carotenoides/análisis , Carotenoides/química , Clorofila/análisis , Clorofila/química , Pigmentos Biológicos/análisis , Pigmentos Biológicos/química
20.
Food Sci Technol Int ; : 10820132241272768, 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39129370

RESUMEN

An increasing number of consumers demand healthier, more convenient, and sustainable food products, including rice, a staple worldwide. Food manufacturers have responded to this trend by considering food's intrinsic and extrinsic aspects. This study evaluated the importance of variety, processing, and claims on willingness to try ready-to-eat rice (RTE-rice). It also analyses the influence of consumer attitudes on the importance of attributes and willingness to try. The results showed that processing significantly influenced willingness to try RTE-rice, revealing consumers' greater preference for whole grain than milled rice with added bran. Claims had the least relevant importance. However, low glycaemic index had a positive impact, indicating its potential to influence consumer purchasing attitudes and promote healthier rice consumption. Additionally, three groups were created based on attitudinal factors. Naturalness-oriented and convenience-oriented groups were more likely to try RTE-rice. However, the reasons that motivate them may be different; this latter could be the ease of the service offered, while for the group focused on naturalness, they may have perceived through the ingredients and claimed that the product, despite being convenient, can bring benefits, thus perceiving them as natural.

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