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1.
EMBO Rep ; 25(9): 3990-4012, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39075237

RESUMEN

Metabolic dysregulation is one of the most common causes of pediatric neurodegenerative disorders. However, how the disruption of ubiquitous and essential metabolic pathways predominantly affect neural tissue remains unclear. Here we use mouse models of a childhood neurodegenerative disorder caused by AMPD2 deficiency to study cellular and molecular mechanisms that lead to selective neuronal vulnerability to purine metabolism imbalance. We show that mouse models of AMPD2 deficiency exhibit predominant degeneration of the hippocampal dentate gyrus, despite a general reduction of brain GTP levels. Neurodegeneration-resistant regions accumulate micron-sized filaments of IMPDH2, the rate limiting enzyme in GTP synthesis, while these filaments are barely detectable in the hippocampal dentate gyrus. Furthermore, we show that IMPDH2 filament disassembly reduces GTP levels and impairs growth of neural progenitor cells derived from individuals with human AMPD2 deficiency. Together, our findings suggest that IMPDH2 polymerization prevents detrimental GTP deprivation, opening the possibility of exploring the induction of IMPDH2 assembly as a therapy for neurodegeneration.


Asunto(s)
AMP Desaminasa , IMP Deshidrogenasa , Enfermedades Neurodegenerativas , Animales , Humanos , Ratones , Modelos Animales de Enfermedad , Guanosina Trifosfato/metabolismo , IMP Deshidrogenasa/metabolismo , IMP Deshidrogenasa/genética , Ratones Noqueados , Células-Madre Neurales/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/etiología , Esfingomielina Fosfodiesterasa , AMP Desaminasa/deficiencia , AMP Desaminasa/metabolismo
2.
Genes Immun ; 25(2): 158-167, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38570727

RESUMEN

In this study, antibody response and a single-cell RNA-seq analysis were conducted on peripheral blood mononuclear cells from five different groups: naïve subjects vaccinated with AZD1222 (AZ) or Ad5-nCoV (Cso), individuals previously infected and later vaccinated (hybrid) with AZD1222 (AZ-hb) or Ad5-nCoV (Cso-hb), and those who were infected and had recovered from COVID-19 (Inf). The results showed that AZ induced more robust neutralizing antibody responses than Cso. The single-cell RNA data revealed a high frequency of memory B cells in the Cso and Cso-hb. In contrast, AZ and AZ-hb groups exhibited the highest proportion of activated naïve B cells expressing CXCR4. Transcriptomic analysis of CD4+ and CD8+ T cells demonstrated a heterogeneous response following vaccination, hybrid immunity, or natural infection. However, a single dose of Ad5-nCoV was sufficient to strongly activate CD4+ T cells (naïve and memory) expressing ANX1 and FOS, similar to the hybrid response observed with AZ. An interesting finding was the robust activation of a subset of CD8+ T cells expressing GZMB, GZMH, and IFNG genes in the Cso-hb group. Our findings suggest that both vaccines effectively stimulated the cellular immune response; however, the Ad5-nCoV induced a more robust CD8+ T-cell response in previously infected individuals.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Linfocitos T CD8-positivos , Adenoviridae/genética , ChAdOx1 nCoV-19 , Leucocitos Mononucleares , Perfilación de la Expresión Génica , Inmunidad Adaptativa , Anticuerpos Neutralizantes/genética , Anticuerpos Antivirales/genética
3.
J Med Virol ; 96(8): e29851, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39132689

RESUMEN

Here, we performed single-cell RNA sequencing of S1 and receptor binding domain protein-specific B cells from convalescent COVID-19 patients with different clinical manifestations. This study aimed to evaluate the role and developmental pathway of atypical memory B cells (MBCs) in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The results revealed a proinflammatory signature across B cell subsets associated with disease severity, as evidenced by the upregulation of genes such as GADD45B, MAP3K8, and NFKBIA in critical and severe individuals. Furthermore, the analysis of atypical MBCs suggested a developmental pathway similar to that of conventional MBCs through germinal centers, as indicated by the expression of several genes involved in germinal center processes, including CXCR4, CXCR5, BCL2, and MYC. Additionally, the upregulation of genes characteristic of the immune response in COVID-19, such as ZFP36 and DUSP1, suggested that the differentiation and activation of atypical MBCs may be influenced by exposure to SARS-CoV-2 and that these genes may contribute to the immune response for COVID-19 recovery. Our study contributes to a better understanding of atypical MBCs in COVID-19 and the role of other B cell subsets across different clinical manifestations.


Asunto(s)
COVID-19 , Células B de Memoria , SARS-CoV-2 , Análisis de la Célula Individual , Humanos , COVID-19/inmunología , COVID-19/virología , COVID-19/genética , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Células B de Memoria/inmunología , Masculino , Adulto , Femenino , Persona de Mediana Edad , Perfilación de la Expresión Génica , Transcriptoma , Centro Germinal/inmunología , Linfocitos B/inmunología , Anciano
4.
Genet Sel Evol ; 56(1): 12, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347496

RESUMEN

BACKGROUND: Intramuscular fat (IMF) content and its fatty acid (FA) composition are typically controlled by several genes, each with a small effect. In the current study, to pinpoint candidate genes and putative regulators involved in FA composition, we performed a multivariate integrative analysis between intramuscular FA and transcriptome profiles of porcine longissimus dorsi (LD) muscle. We also carried out a combination of network, regulatory impact factor (RIF), in silico prediction of putative target genes, and functional analyses to better support the biological relevance of our findings. RESULTS: For this purpose, we used LD RNA-Seq and intramuscular FA composition profiles of 129 Iberian × Duroc backcrossed pigs. We identified 378 correlated variables (13 FA and 365 genes), including six FA (C20:4n-6, C18:2n-6, C20:3n-6, C18:1n-9, C18:0, and C16:1n-7) that were among the most interconnected variables in the predicted network. The detected FA-correlated genes include genes involved in lipid and/or carbohydrate metabolism or in regulation of IMF deposition (e.g., ADIPOQ, CHUK, CYCS, CYP4B1, DLD, ELOVL6, FBP1, G0S2, GCLC, HMGCR, IDH3A, LEP, LGALS12, LPIN1, PLIN1, PNPLA8, PPP1R1B, SDR16C5, SFRP5, SOD3, SNW1, and TFRC), meat quality (GALNT15, GOT1, MDH1, NEU3, PDHA1, SDHD, and UNC93A), and transport (e.g., EXOC7 and SLC44A2). Functional analysis highlighted 54 over-represented gene ontology terms, including well-known biological processes and pathways that regulate lipid and carbohydrate metabolism. RIF analysis suggested a pivotal role for six transcription factors (CARHSP1, LBX1, MAFA, PAX7, SIX5, and TADA2A) as putative regulators of gene expression and intramuscular FA composition. Based on in silico prediction, we identified putative target genes for these six regulators. Among these, TADA2A and CARHSP1 had extreme RIF scores and present novel regulators in pigs. In addition, the expression of TADA2A correlated (either positively or negatively) with C20:4n-6, C18:2n-6, C20:3n-6, C18:1n-9, and that of CARHSP1 correlated (positively) with the C16:1n-7 lipokine. We also found that these two transcription factors share target genes that are involved in lipid metabolism (e.g., GOT1, PLIN1, and TFRC). CONCLUSIONS: This integrative analysis of muscle transcriptome and intramuscular FA profile revealed valuable information about key candidate genes and potential regulators for FA and lipid metabolism in pigs, among which some transcription factors are proposed to control gene expression and modulate FA composition differences.


Asunto(s)
Ácidos Grasos , Músculo Esquelético , Porcinos/genética , Animales , Ácidos Grasos/metabolismo , Músculo Esquelético/metabolismo , Perfilación de la Expresión Génica , Factores de Transcripción/metabolismo , Genes Reguladores , Transcriptoma
5.
Int J Mol Sci ; 25(20)2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39457000

RESUMEN

The associations among increased pain sensitivity, obesity, and systemic inflammation have not been described as related to BBB dysfunctions. To analyze the metabolic, behavioral, and inflammatory effects of a high-fat diet (HFD) and ultrastructural modifications in brain regions, we used an in vivo experimental model. Adult male Wistar rats were randomly assigned to one of two conditions, an ad libitum control group or an HFD (60%)-fed group, for eight weeks. At the end of the protocol, glucose and insulin tolerance tests were performed. Additionally, we analyzed the response to a normally innocuous mechanical stimulus and changes in motor coordination. At the end of the protocol, HFD-fed rats presented increased HOMA-IR and metabolic syndrome (MetS) prevalence. HFD-fed rats also developed an increased nociceptive response to mechanical stimuli and neurological injury, resulting in impaired motor function. Hypothalamus and cerebellum neurons from HFD-fed rats presented with nuclear swelling, an absence of nucleoli, and karyolysis. These results reveal that HFD consumption affects vital brain structures such as the cerebellum, hippocampus, and hypothalamus. This, in turn, could be producing neuronal damage, impairing cellular communication, and consequently altering motricity and pain sensitivity. Although direct evidence of a causal link between BBB dysfunction and sensory-motor changes was not observed, understanding the association uncovered in this study could lead to targeted therapeutic strategies.


Asunto(s)
Barrera Hematoencefálica , Dieta Alta en Grasa , Hiperalgesia , Ratas Wistar , Animales , Dieta Alta en Grasa/efectos adversos , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Masculino , Ratas , Hiperalgesia/etiología , Hiperalgesia/fisiopatología , Hiperalgesia/metabolismo , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Síndrome Metabólico/patología , Resistencia a la Insulina , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología
6.
Europace ; 25(9)2023 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-37669318

RESUMEN

AIMS: Same-day discharge (SDD) is feasible after pulmonary vein isolation (PVI). We aim to compare prospectively cryoballoon (CRYO) vs. radiofrequency (RF) ablation in a systematic SDD programme. METHODS AND RESULTS: We prospectively analysed the 617 scheduled PVI performed consecutively at our institution (n = 377 CRYO, n = 240 RF) from 1 April 2019 to 31 December 2022 within a systematic programme of SDD. The feasibility of SDD, the 10-day incidence of urgent/unplanned medical care after discharge (UUC-10), and the cost per procedure due to hospital resource use were studied. The 100 procedures performed during the previous year, in which patients were systematically hospitalized, were used as a control group. Same-day discharge was achieved in 585/617 (95%) procedures, with a significant trend towards a higher monthly SDD rate from 2019 to 2022 (P = 0.03). The frequency of SDD was similar in CRYO (356/377; 94%) vs. RF (229/240; 95%). After SDD, the UUC-10 was 66/585 (11.3%), being similar for CRYO (41/356; 11.5%) and RF (25/229; 10.9%); P = 0.8 (log-rank test). Of these, 10 patients were re-hospitalized, with an identical rate in CRYO-treated (6/356; 1.7%) and RF-treated (4/229; 1.7%) patients and owing to similar causes (4 haematomas, 4 pericarditis, and 2 symptomatic sinus node dysfunction). Same-day discharge was associated with an average savings per procedure of 63% (P < 0.001), but no differences were found between the CRYO and RF (P = 0.8). CONCLUSION: In a systematic SDD programme, feasibility (95%, increasing over time), safety (11% UUC-10, 1.7% re-hospitalizations), and savings (63% per procedure) were similar for CRYO and RF ablation procedures.


Asunto(s)
Técnicas de Ablación , Venas Pulmonares , Ablación por Radiofrecuencia , Humanos , Alta del Paciente , Venas Pulmonares/cirugía , Hospitalización
7.
Mol Biol Rep ; 50(1): 919-925, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36334231

RESUMEN

BACKGROUND: Previous work showed that the microRNA (miRNA) miR-671-5p was upregulated in monocyte-derived dendritic cells (moDCs) stimulated with Bifidobacterium animalis subsp. lactis BB12 (BB12) with no increase in IL-10 after six hours of stimulation. In this work, we performed an in silico prediction of genes targeted by miR-671-5p and which are the terms and pathways involved with it. Also, miR-671-5p was transiently downregulated to assess its effect on IL-10 regulation. METHODS AND RESULTS: First, we performed a Gene Ontology enrichment analysis to predict immune response terms and pathways involved with miR-671-5p. Some of the terms and pathways found were related to the immune response promoted by the probiotic, as the terms "negative regulation of the inflammatory response to an antigenic stimulus" and "cancer" were highlighted. Then, to assess the role of miR-671-5p in IL-10 regulation, moDCs were derived from porcine peripheral blood and later transfected with miR-671-5p antisense oligonucleotide (ASO). Flow cytometry was employed to evaluate the transfection efficiency. Then, the moDCs were stimulated with BB12, and the expression of IL-10 was assessed by RT-qPCR and ELISA. An increase in IL-10 transcript in miR-671-5p-ASO-transfected moDCs stimulated with BB12 was observed compared with moDCs stimulated with BB12 but not transfected. These results suggest the participation of miR-671-5p as a negative regulator of IL-10. CONCLUSION: These findings suggest that miR-671-5p participates in the downregulation of IL-10, as previously predicted in silico by our work group. miR-671-5p could play an essential role in the immunomodulation promoted by the probiotic BB12.


Asunto(s)
MicroARNs , Probióticos , Porcinos , Animales , Interleucina-10/genética , Interleucina-10/metabolismo , Regulación hacia Abajo/genética , MicroARNs/genética , MicroARNs/metabolismo , Monocitos/metabolismo , ARN Mensajero/metabolismo , Probióticos/farmacología
8.
Environ Res ; 238(Pt 2): 117180, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37739154

RESUMEN

The conversion of biomass waste into high-value nanomaterials such as carbon dots might represent a great advancement towards a circular economy system. Biomass wastes are an excellent choice as carbon precursors because of their wide availability, abundance, chemical composition, and eco-friendly nature. Moreover, their use as a raw material might decrease the total cost of the synthesis processes and reduce the environmental impacts. In addition, the complex composition of biomass leads to carbon dots with abundant functional groups, which in turn enhances water dispersibility and photoluminescence properties. In this manner, the effective transformation of biomass wastes into carbon dots reduces environmental pollution through the inadequate management of waste while producing carbon dots with enhanced performances. Therefore, this review describes biomass wastes as potential candidates for the synthesis of carbon dots through different synthesis methods. In addition, we have analyzed the great potential of biomass-derived carbon dots (CDs) for the degradation and detection of emerging pharmaceutical pollutants by promoting a circular economy approach. Finally, we identified current challenges to propose possible research directions for the large-scale and sustainable synthesis of high-quality biomass-derived CDs.


Asunto(s)
Carbono , Nanoestructuras , Carbono/química , Contaminación Ambiental , Biomasa , Preparaciones Farmacéuticas
9.
Environ Res ; 229: 115892, 2023 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-37084948

RESUMEN

The COVID-19 pandemic has brought increments in market sales and prescription of medicines commonly used to treat mental health disorders, such as depression, anxiety, stress, and related problems. The increasing use of these drugs, named psychiatric drugs, has led to their persistence in aquatic systems (bioaccumulation), since they are recalcitrant to conventional physical and chemical treatments typically used in wastewater treatment plants. An emerging environmental concern caused by the bioaccumulation of psychiatric drugs has been attributed to the potential ecological and toxicological risk that these medicines might have over human health, animals, and plants. Thus, by the application of biocatalysis-assisted techniques, it is possible to efficiently remove psychiatric drugs from water. Biocatalysis, is a widely employed and highly efficient process implemented in the biotransformation of a wide range of contaminants, since it has important differences in terms of catalytic behavior, compared to common treatment techniques, including photodegradation, Fenton, and thermal treatments, among others. Moreover, it is noticed the importance to monitor transformation products of degradation and biodegradation, since according to the applied removal technique, different toxic transformation products have been reported to appear after the application of physical and chemical procedures. In addition, this work deals with the discussion of differences existing between high- and low-income countries, according to their environmental regulations regarding waste management policies, especially waste of the drug industry.


Asunto(s)
COVID-19 , Contaminantes Químicos del Agua , Animales , Humanos , Biocatálisis , Bioacumulación , Pandemias , Agua , Contaminantes Químicos del Agua/análisis , Biodegradación Ambiental
10.
Sensors (Basel) ; 23(8)2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37112379

RESUMEN

The systems used to distribute electricity are currently undergoing a series of changes that are aiding in the development of smart grids.

11.
Sensors (Basel) ; 23(1)2023 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-36617080

RESUMEN

Nowadays, according to the World Health Organization (WHO), of the world's population suffers from a hearing disorder that makes oral communication with other people challenging. At the same time, in an era of technological evolution and digitization, designing tools that could help these people to communicate daily is the base of much scientific research such as that discussed herein. This article describes one of the techniques designed to transcribe Spanish Sign Language (SSL). A Leap Motion volumetric sensor has been used in this research due to its capacity to recognize hand movements in 3 dimensions. In order to carry out this research project, an impaired hearing subject has collaborated in the recording of 176 dynamic words. Finally, for the development of the research, Dynamic Time Warping (DTW) has been used to compare the samples and predict the input with an accuracy of 95.17%.


Asunto(s)
Reconocimiento de Normas Patrones Automatizadas , Lengua de Signos , Humanos , Reconocimiento de Normas Patrones Automatizadas/métodos , Gestos , Movimiento , Movimiento (Física)
12.
Sensors (Basel) ; 23(1)2023 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-36617094

RESUMEN

In recent times, we have been witnessing the development of multiple applications and deployment of services through the indoors location of people as it allows the development of services of interest in areas related mainly to security, guiding people, or offering services depending on their localization. On the other hand, at present, the deployment of Wi-Fi networks is so advanced that a network can be found almost anywhere. In addition, security systems are more demanded and are implemented in many buildings. Thus, in order to provide a non intrusive presence detection system, in this manuscript, the development of a methodology is proposed which is able to detect human presence through the channel state information (CSI) of wireless communication networks based on the 802.11n standard. One of the main contributions of this standard is multiple-input multiple-output (MIMO) with orthogonal frequency division multiplexing (OFDM). This makes it possible to obtain channel state information for each subcarrier. In order to implement this methodology, an analysis and feature extraction in time-domain of CSI is carried out, and it is validated using different classification models trained through a series of samples that were captured in two different environments. The experiments show that the methodology presented in this manuscript obtains an average accuracy above 90%.


Asunto(s)
Extremidad Superior , Humanos
13.
Int J Nurs Pract ; 29(3): e13117, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36478331

RESUMEN

AIMS: We aimed to investigate the perspective of primary care nurses on their role with patients who have chronic cardiovascular disease and to identify cultural elements shared by nurses caring for people with chronic cardiovascular disease. In primary care, the role of the nurse is essential to promote self-efficacy in cardiovascular self-care. Individuals with chronic cardiovascular disease need to integrate the disease into their life, together with the health recommendations for management and follow-up. METHODS: A qualitative, focused ethnographic study was conducted. Purposeful sampling was used to include nurses who were working in primary care during the study. Data collection took place between 20 January and 20 May 2014 and consisted of semi-structured interviews. A thematic analysis was applied using the data. RESULTS: Eleven participants were included. Cardiovascular care forces nurses to reflect on their identity and role in primary care. The relationship between the nurse and people with chronic cardiovascular disease is a complex process, which may cause nurses to feel a sense of failure and monotony in their work. CONCLUSIONS: Our findings may help to understand the role of the nurse and the care provided in patients with chronic cardiovascular disease.


Asunto(s)
Enfermedades Cardiovasculares , Enfermería Cardiovascular , Humanos , Investigación Cualitativa , Antropología Cultural , Enfermedad Crónica , Atención Primaria de Salud
14.
Scand J Immunol ; 95(4): e13136, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34964150

RESUMEN

BACKGROUND AND OBJECTIVES: Glucose-6-phosphate catalytic subunit 3 (G6PC3) deficiency is characterized by severe congenital neutropenia with recurrent pyogenic infections, a prominent superficial venous pattern and cardiovascular and urogenital malformations caused by an alteration of glucose homeostasis, with increased endoplasmic reticulum stress and cell apoptosis. METHODS: We reviewed our patients with G6PC3 deficiency diagnosed along the last decade in Mexico; we also searched the PubMed/Medline database for the terms ('G6PC3 deficiency' OR 'Dursun syndrome' OR 'Severe congenital neutropenia type 4'), and selected articles published in English from 2009 to 2020. RESULTS: We found 89 patients reported from at least 14 countries in 4 continents. We describe five new cases from Mexico. Of the 94 patients, 56% are male, 48% from Middle East countries and none of them had adverse reactions to live vaccines; all presented with at least 1 severe infection prior to age 2. Seventy-five per cent had syndromic features, mainly atrial septal defect in 55% and prominent superficial veins in 62%. CONCLUSIONS: With a total of 94 patients reported in the past decade, we delineate the most frequent laboratory and genetic features, their treatment and outcomes, and to expand the knowledge of syndromic and non-syndromic phenotypes in these patients.


Asunto(s)
Glucosa-6-Fosfatasa , Neutropenia , Dominio Catalítico , Síndromes Congénitos de Insuficiencia de la Médula Ósea , Femenino , Glucosa-6-Fosfatasa/genética , Glucosa-6-Fosfatasa/metabolismo , Humanos , Masculino , Neutropenia/congénito , Neutropenia/genética
15.
J Phys Chem A ; 126(16): 2498-2510, 2022 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-35436116

RESUMEN

We have designed and synthesized two new cyaninic Nd3+ complexes where the lanthanide emission can be induced from simultaneous two-photon absorption followed by energy migration. These complexes correspond to a molecular design that uses an antenna ligand formed by the functionalization of a heptamethine dye with 5-ol-phenanthroline or 4-phenyl-terpyridine derivatives. These complexes employ the important nonlinear optical properties of symmetric polymethines to sensitize the lanthanide ion. We verified that simultaneous biphotonic excitation indirectly induces the 4F3/2 → 4I11/2 Nd3+ emission using femtosecond laser pulses tuned below the first electronic transition of the antenna. The simultaneous two-photon excitation events initially form the nonlinear-active second excited singlet of the polymethine antenna, which rapidly evolves into its first excited singlet. This state in turn induces the formation of the emissive Nd3+ states through energy transfer. The role of the first excited singlet of the antenna as the donor state in this process was verified through time resolution of the antenna's fluorescence. These measurements also provided the rates for antenna-lanthanide energy transfer, which indicate that the phenanthroline-type ligand is approximately five times more efficient for energy transfer than the phenyl-terpyridine derivative due to their relative donor-acceptor distances. The simultaneous two-photon excitation of this polymethine antenna allows for high spatial localization of the Nd3+excitation events.

16.
Proc Natl Acad Sci U S A ; 116(32): 16028-16035, 2019 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-31253706

RESUMEN

Diseases associated with mitochondrial DNA (mtDNA) mutations are highly variable in phenotype, in large part because of differences in the percentage of normal and mutant mtDNAs (heteroplasmy) present within the cell. For example, increasing heteroplasmy levels of the mtDNA tRNALeu(UUR) nucleotide (nt) 3243A > G mutation result successively in diabetes, neuromuscular degenerative disease, and perinatal lethality. These phenotypes are associated with differences in mitochondrial function and nuclear DNA (nDNA) gene expression, which are recapitulated in cybrid cell lines with different percentages of m.3243G mutant mtDNAs. Using metabolic tracing, histone mass spectrometry, and NADH fluorescence lifetime imaging microscopy in these cells, we now show that increasing levels of this single mtDNA mutation cause profound changes in the nuclear epigenome. At high heteroplasmy, mitochondrially derived acetyl-CoA levels decrease causing decreased histone H4 acetylation, with glutamine-derived acetyl-CoA compensating when glucose-derived acetyl-CoA is limiting. In contrast, α-ketoglutarate levels increase at midlevel heteroplasmy and are inversely correlated with histone H3 methylation. Inhibition of mitochondrial protein synthesis induces acetylation and methylation changes, and restoration of mitochondrial function reverses these effects. mtDNA heteroplasmy also affects mitochondrial NAD+/NADH ratio, which correlates with nuclear histone acetylation, whereas nuclear NAD+/NADH ratio correlates with changes in nDNA and mtDNA transcription. Thus, mutations in the mtDNA cause distinct metabolic and epigenomic changes at different heteroplasmy levels, potentially explaining transcriptional and phenotypic variability of mitochondrial disease.


Asunto(s)
Núcleo Celular/genética , ADN Mitocondrial/genética , Epigenoma , Acetilcoenzima A/metabolismo , Línea Celular , Histonas/metabolismo , Humanos , Metaboloma , Mitocondrias/metabolismo , NAD/metabolismo , Transcripción Genética
17.
Sensors (Basel) ; 22(22)2022 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-36433275

RESUMEN

This paper deals with the problem regarding the optimal siting and sizing of distribution static compensators (D-STATCOMs) in electrical distribution networks to minimize the expected total annual operating costs. These costs are associated with the investments made in D-STATCOMs and expected energy losses costs. To represent the electrical behavior of the distribution networks, a power flow formulation is used which includes voltages, currents, and power as variables via incidence matrix representation. This formulation generates a mixed-integer nonlinear programming (MINLP) model that accurately represents the studied problem. However, in light of the complexities involved in solving this MINLP model efficiently, this research proposes a mixed-integer convex reformulation. Numerical results regarding the final annual operating costs of the network demonstrate that the proposed mixed-integer convex model is efficient for selecting and locating D-STATCOMs in distribution networks, with the main advantage that it is applicable to radial and meshed distribution grid configurations. A comparative analysis with respect to metaheuristic optimizers and convex approximations confirms the robustness of the proposed formulation. All numerical validations were conducted in the MATLAB programming environment with our own scripts (in the case of metaheuristics) and the CVX convex disciplined tool via the Gurobi solver. In addition, the exact MINLP model is solved using the GAMS software.

18.
Sensors (Basel) ; 22(8)2022 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-35458899

RESUMEN

This paper analyzes the power flow solution in bipolar direct current networks with radial structures considering multiple monopolar and bipolar constant power loads. The electrical configuration of the bipolar DC grid considers that the reference pole is non-grounded along the feeder, which produces important neutral currents and voltage imbalances along the DC grid. The power flow problem is formulated through the triangular-based representation of the grid topology, which generates a recursive formulation that allows determining the voltage values in the demand nodes through an iterative procedure. The linear convergence of the triangular-based power flow method is tested through multiple load variations with respect to the nominal grid operative condition. Numerical results in the 21- and the 85-bus grids reveal the relevant variations in the voltage profiles and total grid power losses when the neutral cable is solidly grounded or not.

19.
Sensors (Basel) ; 22(3)2022 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-35161597

RESUMEN

This paper discusses the minimization of the total annual operative cost for a planning period of 20 years composed by the annualized costs of the energy purchasing at the substation bus summed with the annualized investment costs in photovoltaic (PV) sources, including their maintenance costs in distribution networks based on their optimal siting and sizing. This problem is presented using a mixed-integer nonlinear programming model, which is resolved by applying a master-slave methodology. The master stage, consisting of a discrete-continuous version of the Vortex Search Algorithm (DCVSA), is responsible for providing the optimal locations and sizes for the PV sources-whereas the slave stage employs the Matricial Backward/Forward Power Flow Method, which is used to determine the fitness function value for each individual provided by the master stage. Numerical results in the IEEE 33- and 69-node systems with AC and DC topologies illustrate the efficiency of the proposed approach when compared to the discrete-continuous version of the Chu and Beasley genetic algorithm with the optimal location of three PV sources. All the numerical validations were carried out in the MATLAB programming environment.

20.
J Fish Biol ; 101(6): 1557-1568, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36181378

RESUMEN

Our understanding of fish life-history strategies is informed by key biological processes, such as growth, survival/mortality, recruitment and sexual maturation, used to characterize fish stocks (populations). Characterizing the life-history traits of fish populations requires the application of accurate age estimation for managed species. Grey triggerfish Balistes capriscus and queen triggerfish Balistes vetula are important reef-associated species for commercial and recreational fisheries in the Atlantic Ocean. Both species exhibit a unique reproductive strategy for large-bodied fisheries-targeted reef fishes in that they are nesting benthic spawners and invest substantial energy in defence and care of their benthic nests and fertilized eggs. Until recently, our understanding of the life-history strategies of triggerfishes assumed the main method used to obtain age estimates, increments counted from thin sections of the first dorsal spine, provided an accurate characterization of population age-based parameters. However, results from bomb radiocarbon validation studies on the two Balistes species demonstrated that spines do not provide accurate ages, but sagittal otoliths do. The main goal of the current study was to provide an updated understanding for triggerfish life-history strategies by using otolith-based age estimates to characterize population age structure and growth for grey triggerfish and queen triggerfish from waters of the south-eastern U.S. Atlantic. The current study is the first to report on sex-specific age and growth information for grey triggerfish using the Δ14 C-validated otolith-based age estimation method and the results indicate that the previous characterization of Balistes species as exhibiting moderately rapid growth and as relatively short-lived, based on spine-derived age estimates, are flawed. Otolith-based ages indicated that grey triggerfish and queen triggerfish are moderately slow-growing and long-lived species, attaining maximum ages of 21 and 40 years, respectively. Management efforts for triggerfishes should evaluate these new insights and incorporate the results of otolith-based age estimation into future population monitoring efforts.


Asunto(s)
Tetraodontiformes , Femenino , Masculino , Animales , Peces , Explotaciones Pesqueras , Océano Atlántico
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