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1.
Sci Rep ; 14(1): 7460, 2024 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-38553497

RESUMEN

Soil salinity and sodicity is a worldwide problem that affects the composition and activity of bacterial communities and results from elevated salt and sodium contents. Depending on the degree of environmental pressure and the combined effect of other factors, haloalkalitolerant and haloalkaliphilic bacterial communities will be selected. These bacteria play a potential role in the maintenance and restoration of salt-affected soils; however, until recently, only a limited number of studies have simultaneously studied the bacterial diversity and activity of saline-sodic soils. Soil samples were collected to analyse and compare the taxonomic composition and metabolic activity of bacteria from four distinct natural plant communities at three soil depths corresponding to a salinity‒sodicity gradient. Bacterial diversity was detected using 16S rRNA gene Illumina MiSeq amplicon sequencing. Community-level physiological profiles (CLPPs) were analysed using the MicroResp™ method. The genus-level bacterial composition and CLPPs differed significantly in soils with different alkaline vegetation. The surface soil samples also significantly differed from the intermediate and deep soil samples. The results showed that the pH, salt content, and Na+ content of the soils were the main edaphic factors influencing both bacterial diversity and activity. With salinity and pH, the proportion of the phylum Gemmatimonadota increased, while the proportions of Actinobacteriota and Acidobacteriota decreased.


Asunto(s)
Salinidad , Suelo , Suelo/química , ARN Ribosómico 16S/genética , Microbiología del Suelo , Bacterias/genética
2.
J Neurol ; 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38436682

RESUMEN

Several neurological manifestations are part of the post-COVID condition. We aimed to: (1) evaluate the 6-month outcome in the cohort of patients with neurological manifestations during the COVID-19 acute phase and surviving the infection, and find outcome predictors; (2) define the prevalence and type of neurological symptoms persistent at six months after the infection. Data source was an international registry of patients with COVID-19 infection and neurological symptoms, signs or diagnoses established by the European Academy of Neurology. Functional status at six-month follow-up was measured with the modified Rankin scale (mRS), and defined as: "stable/improved" if the mRS at six months was equal as or lower than the baseline score; "worse" if it was higher than the baseline score. By October 30, 2022, 1,003 lab-confirmed COVID-19 patients were followed up for a median of 6.5 months. Compared to their pre-morbid status, 522 patients (52%) were stable/improved, whereas 465 (46%) were worse (functional status missing for 16). Age, hospitalization, several pre-COVID-19 comorbidities, and COVID-19 general complications were predictors of a worse status. Amongst neurological manifestations, stroke carried the highest risk for worse outcome (OR 5.96), followed by hyperactive delirium (2.8), and peripheral neuropathies (2.37). On the other hand, hyposmia/hypogeusia (0.38), headache (0.40), myalgia (0.45), and COVID-19 vaccination (0.52) were predictors of a favourable prognosis. Persisting neurological symptoms or signs were reported by 316/1003 patients (31.5%), the commonest being fatigue (n = 133), and impaired memory or concentration (n = 103). Our study identified significant long-term prognostic predictors in patients with COVID-19 and neurological manifestations.

3.
Heliyon ; 10(3): e24959, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38317974

RESUMEN

This study provides a general observation of the status of naturally occurring radioactive materials (NORMs) distribution in mining and industrial areas of Ghana in order to establish regional and national data on NORMs. The study includes data on radioactivity concentrations of U-238, Th-232, and K-40 in soils and for water concentrations of Ra-226, Th-228, and K-40 from various mining, oil, and gas communities, as well as water sources used for crop farming and farmlands. The average activity concentrations of U-238, Th-232, and K-40 in the soil samples were found to be 59 ± 16 Bq/kg, 48 ± 15 Bq/kg, and 286 ± 57 Bq/kg, respectively. The average concentration of Ra-226, Th-228, and K-40 in the water samples were found to be 1.62 ± 0.33 Bq/L, 2.08 ± 0.53 Bq/L, and 22.36 ± 3.44 Bq/L, respectively. The estimated average annual effective doses from external and internal exposure pathways in soil and water samples were 0.09 mSv/y and 0.54 mSv/y, respectively. The total annual effective dose resulting from both exposure pathways was calculated to be 0.63 mSv/y, which is below the 1 mSv/y dose limit recommended by the International Commission on Radiological Protection (ICRP) for controlling public radiation exposure. Based on the radiological hazard indices, the majority of the soil samples were found to be suitable as building materials as their respective indices were below the limits except for two sample locations and the sludge and scale samples. The average Excess Lifetime Cancer Risk (ELCR) value of the water samples was 1.6 times greater than the recommended value of 1.16 × 10-3, presenting a relatively higher risk to the public of developing cancer. No significant regional differences in the levels of radioactive elements. The regression models demonstrate strong interrelationships between the studied elements, with high R-squared values suggesting a predictable nature of one element's concentration based on others.

4.
Ideggyogy Sz ; 77(1-2): 51-59, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38321854

RESUMEN

Background and purpose:

Neuro­cog­nitive aging and the associated brain diseases impose a major social and economic burden. Therefore, substantial efforts have been put into revealing the lifestyle, the neurobiological and the genetic underpinnings of healthy neurocognitive aging. However, these studies take place almost exclusively in a limited number of highly-developed countries. Thus, it is an important open question to what extent their findings may generalize to neurocognitive aging in other, not yet investigated regions. The purpose of the Hungarian Longitudinal Study of Healthy Brain Aging (HuBA) is to collect multi-modal longitudinal data on healthy neurocognitive aging to address the data gap in this field in Central and Eastern Europe.

. Methods:

We adapted the Australian Ima­ging, Biomarkers and Lifestyle (AIBL) study of aging study protocol to local circumstances and collected demographic, lifestyle, men­tal and physical health, medication and medical history related information as well as re­cor­ded a series of magnetic resonance imaging (MRI) data. In addition, participants were al­so offered to participate in the collection of blood samples to assess circulating in­flam­matory biomarkers as well as a sleep study aimed at evaluating the general sleep quality based on multi-day collection of subjective sleep questionnaires and whole-night elec­troencephalographic (EEG) data.

. Results:

Baseline data collection has al­ready been accomplished for more than a hundred participants and data collection in the se­cond
session is on the way. The collected data might reveal specific local trends or could also indicate the generalizability of previous findings. Moreover, as the HuBA protocol al­so offers a sleep study designed for tho­rough characterization of participants’ sleep quality and related factors, our extended multi-modal dataset might provide a base for incorporating these measures into healthy and clinical aging research. 

. Conclusion:

Besides its straightforward na­tional benefits in terms of health ex­pen­di­ture, we hope that this Hungarian initiative could provide results valid for the whole Cent­ral and Eastern European region and could also promote aging and Alzheimer’s disease research in these countries.

.


Asunto(s)
Envejecimiento , Encéfalo , Masculino , Humanos , Estudios Longitudinales , Hungría , Australia , Encéfalo/patología , Envejecimiento/patología , Biomarcadores
5.
J Clin Med ; 13(4)2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38398303

RESUMEN

Background: IgA nephropathy (IgAN) is associated with chronic inflammation. Platelet-related parameters, such as the platelet (PLT) count, platelet-to-albumin ratio (PAR), and platelet-to-lymphocyte ratio (PLR), were examined as potential prognostic indicators for renal and cardiovascular (CV) outcomes in IgAN. We were interested in whether platelet-related parameters are risk factors for ESKD and CV events in IgAN patients. Methods: In a monocentric retrospective study, 124 IgAN patients were divided into two groups based on the cut-off value of the PAR. All-cause mortality, major CV events, and end-stage renal disease were the primary combined endpoints. Secondary endpoints, such as CV or renal endpoints, were also analyzed separately. Results: The patients' mean age was 43.7 ± 13.5 years, and the follow-up time was 124 ± 67 months. The K-M curve showed that the PLR, PAR, and PLT were strongly associated with primary combined (p = 0.002, p = 0.004, p = 0.001) and renal outcomes (p < 0.001, p < 0.001, p < 0.001), but not with CV outcomes in IgAN. However, when combined with left ventricular hypertrophy (LVH) or metabolic syndrome (MetS), the PAR was found to be a significant predictor of both primary (p < 0.001, p < 0.001) and secondary outcomes (p = 0.001 and p = 0.038; p = 0.001 and p = 0.015). Additionally, the PLR correlated with albuminuria (r = -0.165, p = 0.033) and LVH (r = -0.178, p = 0.025), while PLT correlated with eGFR (r = 0.158, p = 0.040). Conclusions. Elevated PARs and PLRs may predict progression to end-stage kidney disease, but in combination with LVH and MetS, they were related to CV events in IgAN. The determination of PARs and PLRs can be useful and cost-effective parameters for assessing both cardiovascular and renal risks in IgAN.

6.
Sci Rep ; 14(1): 1391, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38228676

RESUMEN

This study investigates the last two centuries sedimentation dynamics in four high-altitude lakes located in Southern Carpathians, Romania. Furthermore, a novel approach is proposed for identifying the anthropic or natural underlying causes, by comparison of the acceleration of the change in sedimentation rate with a baseline growth rate trend provided by an isolated peat bog. The high-resolution chronologies were developed using the 210Pb dating technique and the CRS model. 137Cs alternative time-marker validated the age-depth models and reassured the quality of the results. The results indicated several short-interval high sedimentation events within the lake cores, yielding up to five times the average rate for the investigated period. The cause of the high sedimentation episodes was generally attributed to anthropic activities (primarily road construction) and extreme natural events. A first-order derivative equation was employed to plot the acceleration in the sedimentation rate of the lakes with the peat bog baseline. The discrepancies between the acceleration trends highlighted significant deviations from the natural variation tendencies and provided preliminary data regarding the underlying causes of the intense sedimentation periods.

7.
Int J Cardiovasc Imaging ; 40(2): 307-319, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37935940

RESUMEN

In chronic kidney disease (CKD), as in IgA nephropathy (IgAN), cardiovascular (CV) mortality and morbidity are many times higher than in the general population, and diastolic dysfunction (LVDD) has prognostic significance as well. Tissue Doppler Echocardiography (TDI) is another method for measuring myocardial contractility and determining diastolic dysfunction. 79 IgAN patients (age 46 ± 11 years) with CKD stages 1-3 were investigated and followed for 70 ± 28.7 months. Doppler echocardiography was used to measure the E (early) and A (late) waves, as well as the E wave deceleration time (EDT) during mitral inflow. TDI was used to measure early (Ea) and late (Aa) diastolic velocities (lateral and septal basal wall fragment average). From these, we calculated the E/Ea and Ea/Aa ratios. The primary combined endpoints were total mortality, major CV events, and end-stage renal disease, and the secondary endpoints were cardiovascular or renal (eGFR decreased below 15 ml/min/1.73 m2 or renal replacement therapy was started). Patients with decreased Ea (< 13 cm/s) had significantly more endpoints (20/42 vs. 3/37; p = 0.001) than patients with higher Ea (≥ 13 cm/s). The secondary renal endpoints were also significantly higher (p = 0.004). In a multivariate model, the eGFR showed independent correlation with the E/A ratio (r = 0.466; p < 0.01), EDT (r = - 0.270; p < 0.01), Ea/Aa ratio (r = 0.455; p < 0.01), and decreased Ea (r = 0.544; p < 0.01). Independent factors influencing Ea were only EDT by uni- and multivariate regression but age and albuminuria by logistic regression. Decreased Ea measured by TDI seems to be an eligible factor to predict the prognosis of IgA nephropathy. The decreased Ea may be a helpful parameter to identify high-risk CKD patients.


Asunto(s)
Glomerulonefritis por IGA , Fallo Renal Crónico , Disfunción Ventricular Izquierda , Humanos , Adulto , Persona de Mediana Edad , Pronóstico , Glomerulonefritis por IGA/diagnóstico por imagen , Valor Predictivo de las Pruebas , Ecocardiografía , Diástole
8.
Sci Rep ; 13(1): 21934, 2023 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-38082027

RESUMEN

Previous research has not demonstrated secondary degeneration of the spinal cord (SpC) motoneurons after cerebral infarct. The aim of the present study is to investigate the involvement of the anterior horn cells (AHC) in the early post-stroke period using histomorphological and immunohistochemical methods. Post-mortem analysis of the 6th cervical segment was performed in 7 patients who had total MCA stroke within 1 month before death. Nissl-stained sections were used for morphometry, while CD68 and synaptophysin (SYP) immunohistochemistry to monitor microglial activation and synaptic changes in the anterior horn (AH), respectively. Contralateral to the cerebral lesion (contralesional side), cells were smaller after 3 days and larger after 1 week of stroke, especially regarding the large alpha motoneurons. CD68 density increased mainly on the contralesional Rexed's IX lamina of the SpC. SYP coverage of the large motoneurons was reduced on the contralesional side. Early microglial activation in the AH and electrophysiological signs has suggested the possibility of impairment of anterior horn cells (AHC-s). Our study supported that early microglial activation in the contralesional side of the SpC may primarily affect the area corresponding to the location of large motoneurons, and is accompanied by a transient shrinkage followed by increase in size of the large AHC-s with a reduction of their synaptic coverage. After MCA stroke, early involvement of the SpC motoneurons may be suspected by their morphological and synaptic changes and by the pattern of microglial activation.


Asunto(s)
Médula Espinal , Accidente Cerebrovascular , Humanos , Médula Espinal/patología , Neuronas Motoras/fisiología , Células del Asta Anterior/patología , Accidente Cerebrovascular/patología , Degeneración Walleriana/patología
9.
Int J Mol Sci ; 24(19)2023 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-37834309

RESUMEN

N6-methyladenine (6mA) in the DNA is a conserved epigenetic mark with various cellular, physiological and developmental functions. Although the presence of 6mA was discovered a few years ago in the nuclear genome of distantly related animal taxa and just recently in mammalian mitochondrial DNA (mtDNA), accumulating evidence at present seriously questions the presence of N6-adenine methylation in these genetic systems, attributing it to methodological errors. In this paper, we present a reliable, PCR-based method to determine accurately the relative 6mA levels in the mtDNA of Caenorhabditis elegans, Drosophila melanogaster and dogs, and show that these levels gradually increase with age. Furthermore, daf-2(-)-mutant worms, which are defective for insulin/IGF-1 (insulin-like growth factor) signaling and live twice as long as the wild type, display a half rate at which 6mA progressively accumulates in the mtDNA as compared to normal values. Together, these results suggest a fundamental role for mtDNA N6-adenine methylation in aging and reveal an efficient diagnostic technique to determine age using DNA.


Asunto(s)
Metilación de ADN , ADN Mitocondrial , Animales , Perros , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Adenina/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Envejecimiento/genética , Mamíferos/metabolismo
10.
Heliyon ; 9(9): e19813, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37809865

RESUMEN

Radiation exposure due to all-natural sources amounts to about 2.4 mSv per year. However, this amount might be changed to over 3 mSv y-1 according to the recently introduced ICRP radon dose coefficient factor. Previously, the radon contribution to the total dose from natural sources was about 1.2 mSv y-1. However, after the latest introduced dose conversion factor by ICRP, this value could technically be increased to around 2 mSv y-1. This paper attempts to address the following questions: (i) whether reducing radon concentration to the recommended level could address concerns about radiation exposure in underground workplaces, and (ii) the effects of the difference between the epidemiological dosimetry models and realistic dose estimation. The actual dose conversion factor (DCF) was calculated using measured annual average unattached and equilibrium factors, ranging from 16 ± 9 to 25 ± 10 mSv·WLM-1. Then, the estimated inhalation dose, both from self-calculated DCF and the value reported by ICRP-137, was compared: 5.6 ± 0.7-7.6 ± 0.9 mSv y-1 and 3.3 ± 0.4-3.6 ± 0.5 mSv y-1, respectively. It can be observed that exposure to a radon concentration lower than the recommended level does not guarantee a lower dose than the recommended value. The estimated dose was at least two times greater than the dose using pre-estimated values from epidemiological dosimetry models, specifically in this case study. Further experiments in different underground working environments, excluding caves, are needed for more precise observations. It might also be time to update the data regarding the dose contribution from natural radiation sources, as the radon contribution increased according to ICRP.

11.
BMC Nephrol ; 24(1): 261, 2023 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-37661275

RESUMEN

AIM: In chronic kidney disease, IgA nephropathy, and left ventricular diastolic dysfunction have prognostic significance as well. However, the relationship between diastolic dysfunction, arterial stiffness, and renal function has not been fully elucidated. METHODS: 79 IgA nephropathy patients (aged 46 ± 11 years) and 50 controls were investigated. Tissue Doppler imaging was used to measure early (Ea) and late (Aa) diastolic velocities. Arterial stiffness was measured by a photoplethysmographic (stiffness index (SI)) and an oscillometric method (aortic pulse wave velocity (PWVao)). RESULTS: We compared the IgAN patients to a similar cardiovascular risk group with a preserved eGFR. A strong correlation was found between Ea/Aa and SI (p < 0.001), also with PWVao (p < 0.001), just in IgAN, and with eGFR (p < 0.001) in both groups. IgAN patients were divided into groups CKD1-2 vs. CKD3-5. In the CKD 3-5 group, the incidence of diastolic dysfunction increased significantly: 39% vs. 72% (p = 0.003). Left ventricle rigidity (LVR) was calculated, which showed a close correlation with SI (p = 0.009) and eGFR (p = 0.038). By linear regression analysis, the independent predictors of SI were age, E/A, and E/Ea; SI was the predictor of LVR; and E/A and hypertension were the predictors of eGFR. CONCLUSION: In chronic kidney disease, increased cardiac rigidity and vascular stiffness coexist with decreased renal function, which is directly connected to diastolic dysfunction and vascular stiffness. On the basis of comparing the CKD group to the control group, vascular alterations in very early CKD can be identified.


Asunto(s)
Glomerulonefritis por IGA , Rigidez Vascular , Humanos , Análisis de la Onda del Pulso , Función Ventricular Izquierda , Riñón/fisiología
12.
PLoS One ; 18(9): e0292125, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37768988

RESUMEN

This study aimed to survey the long-term effects of fertilization practices on the functional diversity of the soil microbiota. A 60-year fertilization experiment with mineral fertilizers, farmyard manure and combined treatments was sampled in two consecutive years in maize (Zea mays L.) and wheat (Triticum aestivum L.). Soil chemical properties, plant growth and physiological parameters were measured. The MicroRespTM method was applied to assess the community level physiological profiles (CLPPs) of the rhizosphere soil, and the arbuscular mycorrhizal fungal (AMF) colonization of the roots was determined. Samples were taken in the early vegetative stages, at flowering, and at harvest in both years. The measured parameters were analysed using multifactorial ANOVA to determine treatment effects, crop-dependent differences, and seasonality. PCA analysis was performed on the data matrix to reveal more complex correspondences, and Pearson's product-moment correlation was used to confirm relationships between some of the measured soil and plant parameters. Fertilization treatments caused long-term changes in some biological parameters such as: MicroRespTM parameters, citrate utilization, total substrate-induced respiration value, and the ratio of utilization of amino acids and sugars. The rate of AMF colonization responded mainly to the plant nutrition status and the plant requirements, suggesting a plant-mediated effect in the case of mycorrhiza. Mineral nitrogen fertilization and soil acidification were found to be the main factors affecting the catabolic activity of soil microbiota, while AMF colonization responded to the balance of plant nutrition.

13.
Sci Rep ; 13(1): 15690, 2023 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-37735228

RESUMEN

This paper describes the dynamics of 137Cs accumulation and its concentration ratio as well as that of some stable elements in the body, shell, gastrointestinal tract and albumin gland of a particular species of snail (terrestrial gastropod), namely the Giant African snail (Lissachatina fulica), after the long-term ingestion of contaminated forage and/or soil. The activity concentration of 137Cs in the their bodies increased over the first 40 days of the experiment, after which the increase in the activity of this radionuclide significantly reduced. The distribution of 137Cs in the body of a snail decreases as follows: gastrointestinal tract ˃ body = albumin gland ˃ shell. It was found that the contribution of soil towards the contamination of their bodies by 137Cs is far less than that of forage. Although the biological availability of Pb and U in forage is one order of magnitude higher than in soil, the main contribution to the contamination of snails originates from soil.


Asunto(s)
Gastrópodos , Metales Pesados , Animales , Radioisótopos de Cesio , Albúminas , Suelo
14.
Sci Rep ; 13(1): 13611, 2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37604958

RESUMEN

Recently, interest in measuring the concentration of 220Rn in air has increased greatly following the development of standards and the calibration of monitoring instruments. In this study, a 220Rn calibration chamber was designed and developed at the Institute of Radiochemistry and Radioecology (RRI) based on the computational fluid dynamics (CFD) method implemented in ANSYS Fluent 2020 R1 code at the University of Pannonia in Hungary. The behavior of 220Rn and its spatial distribution inside the 220Rn calibration chamber at RRI were investigated at different flow rates. The 220Rn concentration was close to homogeneous under higher flow regimes due to thorough mixing of the gas inside the chamber. Predictions based on CFD simulations were compared with experimentally measured transmission factors (Cout/Cin). The spatial distribution of 220Rn was dependent on the flow rate and the positions of the inlet and outlet. Our results clearly demonstrate the suitability of the 220Rn calibration chamber at RRI for calibrating monitoring instruments. Furthermore, the CFD-based predictions were in good agreement with the results obtained at higher flow rates using experimental and analytical models according to the relative deviation, with a maximum of approximately 9%.

15.
Nat Commun ; 14(1): 5278, 2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37644049

RESUMEN

Mobility of transposable elements (TEs) frequently leads to insertional mutations in functional DNA regions. In the potentially immortal germline, TEs are effectively suppressed by the Piwi-piRNA pathway. However, in the genomes of ageing somatic cells lacking the effects of the pathway, TEs become increasingly mobile during the adult lifespan, and their activity is associated with genomic instability. Whether the progressively increasing mobilization of TEs is a cause or a consequence of ageing remains a fundamental problem in biology. Here we show that in the nematode Caenorhabditis elegans, the downregulation of active TE families extends lifespan. Ectopic activation of Piwi proteins in the soma also promotes longevity. Furthermore, DNA N6-adenine methylation at TE stretches gradually rises with age, and this epigenetic modification elevates their transcription as the animal ages. These results indicate that TEs represent a novel genetic determinant of ageing, and that N6-adenine methylation plays a pivotal role in ageing control.


Asunto(s)
Elementos Transponibles de ADN , Longevidad , Animales , Longevidad/genética , Elementos Transponibles de ADN/genética , Caenorhabditis elegans/genética , Regulación hacia Abajo/genética , Adenina
16.
Cells ; 12(13)2023 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-37443788

RESUMEN

Autophagy is a lysosomal-dependent degradation process of eukaryotic cells responsible for breaking down unnecessary and damaged intracellular components. Autophagic activity gradually declines with age due to genetic control, and this change contributes to the accumulation of cellular damage at advanced ages, thereby causing cells to lose their functionality and viability. This could be particularly problematic in post-mitotic cells including neurons, the mass destruction of which leads to various neurodegenerative diseases. Here, we aim to uncover new regulatory points where autophagy could be specifically activated and test these potential drug targets in neurodegenerative disease models of Drosophila melanogaster. One possible way to activate autophagy is by enhancing autophagosome-lysosome fusion that creates the autolysosome in which the enzymatic degradation happens. The HOPS (homotypic fusion and protein sorting) and SNARE (Snap receptor) protein complexes regulate the fusion process. The HOPS complex forms a bridge between the lysosome and autophagosome with the assistance of small GTPase proteins. Thus, small GTPases are essential for autolysosome maturation, and among these proteins, Rab2 (Ras-associated binding 2), Rab7, and Arl8 (Arf-like 8) are required to degrade the autophagic cargo. For our experiments, we used Drosophila melanogaster as a model organism. Nerve-specific small GTPases were silenced and overexpressed. We examined the effects of these genetic interventions on lifespan, climbing ability, and autophagy. Finally, we also studied the activation of small GTPases in a Parkinson's disease model. Our results revealed that GTP-locked, constitutively active Rab2 (Rab2-CA) and Arl8 (Arl8-CA) expression reduces the levels of the autophagic substrate p62/Ref(2)P in neurons, extends lifespan, and improves the climbing ability of animals during ageing. However, Rab7-CA expression dramatically shortens lifespan and inhibits autophagy. Rab2-CA expression also increases lifespan in a Parkinson's disease model fly strain overexpressing human mutant (A53T) α-synuclein protein. Data provided by this study suggests that Rab2 and Arl8 serve as potential targets for autophagy enhancement in the Drosophila nervous system. In the future, it might be interesting to assess the effect of Rab2 and Arl8 coactivation on autophagy, and it would also be worthwhile to validate these findings in a mammalian model and human cell lines. Molecules that specifically inhibit Rab2 or Arl8 serve as potent drug candidates to modulate the activity of the autophagic process in treating neurodegenerative pathologies. In the future, it would be reasonable to investigate which GAP enzyme can inhibit Rab2 or Arl8 specifically, but not affect Rab7, with similar medical purposes.


Asunto(s)
Proteínas de Unión al GTP Monoméricas , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Animales , Humanos , Drosophila melanogaster/genética , Autofagia/genética , Drosophila/metabolismo , Proteínas SNARE/metabolismo , Neuronas/metabolismo , Envejecimiento , Proteínas de Unión al GTP Monoméricas/metabolismo , Mamíferos/metabolismo
17.
Heliyon ; 9(6): e16690, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37260905

RESUMEN

The natural and artificial radioactivity in beach sediment sampled from the coastline of Ghana were analyzed using High Purity Germanium gamma ray detector. The overall average activity concentrations of 226Ra, 232Th, 40K and 137Cs were estimated to be 43 ± 6, 22 ± 1, 393 ± 74 and 8.4 ± 0.5 Bqkg-1, respectively. Apart from 226Ra the mean activity concentrations of the measured radionuclides were below the world averages of 32, 45, 412 and 18.2 Bqkg-1 respectively. High 137Cs mean concentration of 109.8 Bqkg-1 was observed for one of the locations, which might be due to the occurrence of a nuclear incidence or other factors. The evaluated radiological parameters also had values below world averages, except for some coastal areas which recorded Annual Gonadal Dose Equivalent (AGDE) values higher than the reference level of 300 µSvy-1. There was no significant risk associated with the radionuclide activities evaluated along the coast of Ghana. The correlation between the radionuclides and the radiological parameters were analyzed with the Pearson correlation matrix, cluster and PCA analysis, and they all showed similar outcomes. Spatial distribution maps were also created using ArcGIS software for a pictorial view of the distribution of radionuclides along the study area.

18.
Int J Mol Sci ; 24(12)2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37373483

RESUMEN

Cardiovascular mortality is a leading cause of death in chronic kidney disease (CKD), as is IgA nephropathy (IgAN). The purpose of this study is to find different biomarkers to estimate the outcome of the disease, which is significantly influenced by the changes in vessels (characterized by arterial stiffness) and the heart. In our cross-sectional study, 90 patients with IgAN were examined. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was measured as a heart failure biomarker by an automated immonoassay method, while the carboxy-terminal telopeptide of collagen type I (CITP) as a fibrosis marker was determined using ELISA kits. Arterial stiffness was determined by measuring carotid-femoral pulse wave velocity (cfPWV). Renal function and routine echocardiography examinations were performed as well. Based on eGFR, patients were separated into two categories, CKD 1-2 and CKD 3-5. There were significantly higher NT-proBNP (p = 0.035), cfPWV (p = 0.004), and central aortic systolic pressure (p = 0.037), but not CITP, in the CKD 3-5 group. Both biomarker positivities were significantly higher in the CKD 3-5 group (p = 0.035) compared to the CKD 1-2 group. The central aortic systolic pressure was significantly higher in the diastolic dysfunction group (p = 0.034), while the systolic blood pressure was not. eGFR and hemoglobin levels showed a strong negative correlation, while left ventricular mass index (LVMI), aortic pulse pressure, central aortic systolic pressure, and cfPWV showed a positive correlation with NT-proBNP. cfPWV, aortic pulse pressure, and LVMI showed a strong positive correlation with CITP. Only eGFR was an independent predictor of NT-proBNP by linear regression analysis. NT-proBNP and CITP biomarkers may help to identify IgAN patients at high risk for subclinical heart failure and further atherosclerotic disease.


Asunto(s)
Glomerulonefritis por IGA , Insuficiencia Cardíaca , Insuficiencia Renal Crónica , Rigidez Vascular , Humanos , Análisis de la Onda del Pulso , Estudios Transversales , Biomarcadores , Péptido Natriurético Encefálico , Fragmentos de Péptidos
19.
J Environ Radioact ; 265: 107224, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37356351

RESUMEN

Prediction of areas with elevated natural radiation is fundamental for the prevention of human exposure. Soil gas radon activity concentration and soil gas permeability are predictive parameters for the radon potential, which has great importance in areas where future urban development is planned. In this study, the soil gas radon equilibrium concentration (C∞) and soil gas permeability (K) were estimated through the application of theoretical and empirical models found in the literature. These models apply soil properties as input parameters. Using already existing soil parameters to predict the radon potential of an area would be useful in avoiding direct field measurements. Therefore, in this study, we examined whether the estimated soil gas radon activity concentration and soil gas permeability values match the values measured in the field. The soil gas radon activity concentration estimated by two theoretical models is about 50% of the measured value in the studied area. This underestimation can be attributed to the assumption that the radon activity concentration measured in the field depends only on soil parameters and the models do not take into account the underlying bedrock. Additionally, these models neglect the radon transport by advection and consider only the radon availability and migration in homogeneous media. Furthermore, they do not count certain characteristics of the soil that can be relevant, e.g. organic matter and clay content in the soil. To investigate more in detail such soil characteristics, seven samples located roughly along the slope, were selected to determine the soil chemical composition by ICP-MS. Evaluating the physical and chemical properties of the soil, it was found that the sampling sites with pH < 8 (low calcium content) the preferential adsorption was a dominant process. This causes radium enrichment in organic matter and clay, which directly influence the soil gas radon activity concentration. At pH > 8, radium is no longer preferentially adsorbed on organic matter but continues to be adsorbed on clays albeit this process is weak because radium competes with calcium cations. Also, there are other factors that may affect radon emanation in soil such as radium concentration and distribution, porosity and water content. In contrast, empirical model of soil gas permeability overestimates the measured value in the study area by an order of magnitude. A new model was made by modifying the previously proposed one, which can be used as a guide for the estimation of the median value of soil gas permeability in granitic areas, but not as an accurate predictor due to the lack of correlation between the estimated and measured values.


Asunto(s)
Monitoreo de Radiación , Radio (Elemento) , Radón , Contaminantes Radiactivos del Suelo , Humanos , Radón/análisis , Suelo/química , Arcilla , Radio (Elemento)/análisis , Calcio , Contaminantes Radiactivos del Suelo/análisis , Permeabilidad
20.
Int J Mol Sci ; 24(9)2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-37175806

RESUMEN

Autophagy (cellular self-degradation) plays a major role in maintaining the functional integrity (homeostasis) of essentially all eukaryotic cells. During the process, superfluous and damaged cellular constituents are delivered into the lysosomal compartment for enzymatic degradation. In humans, age-related defects in autophagy have been linked to the incidence of various age-associated degenerative pathologies (e.g., cancer, neurodegenerative diseases, diabetes, tissue atrophy and fibrosis, and immune deficiency) and accelerated ageing. Muscle mass decreases at detectable levels already in middle-aged patients, and this change can increase up to 30-50% at age 80. AUTEN-67 and -99, two small-molecule enhancers of autophagy with cytoprotective and anti-ageing effects have been previously identified and initially characterized. These compounds can increase the life span in wild-type and neurodegenerative model strains of the fruit fly Drosophila melanogaster. Adult flies were treated with these AUTEN molecules via feeding. Fluorescence and electron microscopy and Western blotting were used to assess the level of autophagy and cellular senescence. Flying tests were used to measure the locomotor ability of the treated animals at different ages. In the current study, the effects of AUTEN-67 and -99 were observed on striated muscle cells using the Drosophila indirect flight muscle (IFM) as a model. The two molecules were capable of inducing autophagy in IFM cells, thereby lowering the accumulation of protein aggregates and damaged mitochondria, both characterizing muscle ageing. Furthermore, the two molecules significantly improved the flying ability of treated animals. AUTEN-67 and -99 decrease the rate at which striated muscle cells age. These results may have a significant medical relevance that could be further examined in mammalian models.


Asunto(s)
Drosophila , Músculo Estriado , Animales , Humanos , Persona de Mediana Edad , Anciano de 80 o más Años , Drosophila melanogaster , Envejecimiento , Autofagia , Mamíferos
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