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Redundant manipulators are universally employed to save manpower and improve work efficiency in numerous areas. Nevertheless, the redundancy makes the inverse kinematics of manipulators hard to address, thus increasing the difficulty in instructing manipulators to perform a given task. To deal with this problem, an online learning fuzzy echo state network (OLFESN) is proposed in the first place, which is based upon an online learning echo state network and the Takagi-Sugeno-Kang fuzzy inference system (FIS). Then, an OLFESN-based control scheme is devised to implement the efficient control of redundant manipulators. Furthermore, simulations and experiments on redundant manipulators, covering UR5 and Franka Emika Panda manipulators, are carried out to verify the effectiveness of the proposed control scheme.
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Human error constitutes one of the primary causes of accidents, particularly in the context of loading and unloading operations involving road trucks, especially those carrying petroleum products. The process of identifying and evaluating human errors within these operations involves several key steps. Initially, all sub-tasks associated with loading and unloading are meticulously identified and analyzed utilizing Hierarchical Task Analysis (HTA), achieved through direct observation, document examination, and interviews. Subsequently, potential human error modes within each task are delineated using the Systematic Human Error Reduction and Prediction Approach (SHERPA). Finally, essential data for determining the criticality, probability, and severity of each error are gathered through expert elicitation and the application of Fuzzy Inference Systems (FIS). Through the analysis of SHERPA worksheets, a total of 37 errors during loading operations and 14 errors during unloading operations of petroleum products were identified. Among these errors, the predominant category during loading operations was action errors, comprising 31 instances, while communication errors were the least frequent, occurring only twice. Similarly, action errors were most prevalent during unloading operations, constituting 13 instances. These errors were further categorized and ranked based on their risk levels, resulting in 27 levels for loading operations and 12 levels for unloading operations. The consistent occurrence of action errors underscores the need for implementing control measures to mitigate their frequency and severity. Such strategies may include periodic training sessions to reinforce proper work procedures and the development of monitoring checklists, among other interventions.
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The fixation index, F IS, has been a staple measure to detect selection, or departures from random mating in populations. However, current Next Generation Sequencing (NGS) cannot easily estimate F IS, in multi-locus gene families that contain multiple loci having similar or identical arrays of variant sequences of ≥1 kilobase (kb), which differ at multiple positions. In these families, high-quality short-read NGS data typically identify variants, but not the genomic location, which is required to calculate F IS (based on locus-specific observed and expected heterozygosity). Thus, to assess assortative mating, or selection on heterozygotes, from NGS of multi-locus gene families, we need a method that does not require knowledge of which variants are alleles at which locus in the genome. We developed such a method. Like F IS, our novel measure, 1 H IS, is based on the principle that positive assortative mating, or selection against heterozygotes, and some other processes reduce within-individual variability relative to the population. We demonstrate high accuracy of 1 H IS on a wide range of simulated scenarios and two datasets from natural populations of penguins and dolphins. 1 H IS is important because multi-locus gene families are often involved in assortative mating or selection on heterozygotes. 1 H IS is particularly useful for multi-locus gene families, such as toll-like receptors, the major histocompatibility complex in animals, homeobox genes in fungi and self-incompatibility genes in plants.
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The investigations have shown that the construction of the dam and its related facilities have significant physical-chemical and ecological effects on the ecosystem. Failure Mode and Effects Analysis (FMEA) is a technique for ranking risks in projects to construct dams, but it has many deficiencies and ambiguities. Therefore, to prevent the shortcomings of the classical method, the modified fuzzy inference system (MFIS-FMEA) method has been used by creating a two-stage model to more accurately assess the risk of Eyvashan Dam. First, all the considered indicators are weighted using the Shannon entropy method, and the environmental risk is prioritized using the Fuzzy OWA method. In this study, two-stage fuzzy reasoning and a Max-Min combination rule are used. When severity (SEV) and occurrence (OCC) variables are combined, the critical risk index (RCI) values are predicted in the first stage. RCI and detection index (DET) input are then used to predict the MFIS-RPN in the second stage. The results of the risk priority number (RPN) in the MFIS-RPN method are much more accurate and serious than the FIS-RPN method due to the two-stage nature and the use of new language terms. The results of the proposed MFIS-RPN technique show that the highest RPN was obtained with immediate action in the dam construction phase for soil erosion and soil pollution and in the dam operation phase for aquatic and water pollution. Therefore, due to the increase in risk score, it is necessary to take immediate and more accurate monitoring during the construction and operation phases.
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Triple-negative breast cancer (TNBC) still one of the most challenging sub-type in breast cancer clinical. Caffeic acid (CA) derived from effective components of traditional Chinese herbal medicine has been show potential against TNBCs. Our research has found that CA can inhibit the proliferation of TNBC cells while also suppressing the size of cancer stem cell spheres. Additionally, it reduces reactive oxygen species (ROS) levels and disruption of mitochondrial membrane potential. Simultaneously, CA influences the stemness of TNBC cells by reducing the expression of the stem cell marker protein CD44. Furthermore, we have observed that CA can modulate the FOXO1/FIS signaling pathway, disrupting mitochondrial function, inducing mitochondrial autophagy, and exerting anti-tumor activity. Additionally, changes in the immune microenvironment were detected using a mass cytometer, we found that CA can induce M1 polarization of macrophages, enhancing anti-tumor immune responses to exert anti-tumor activity. In summary, CA can be considered as a lead compound for further research in targeting TNBC.
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Ácidos Cafeicos , Proliferación Celular , Transducción de Señal , Neoplasias de la Mama Triple Negativas , Animales , Femenino , Humanos , Ratones , Autofagia/efectos de los fármacos , Ácidos Cafeicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proteína Forkhead Box O1/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos BALB C , Ratones Desnudos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Microambiente Tumoral/efectos de los fármacosRESUMEN
Intestinal diseases often stem from a compromised intestinal barrier. This barrier relies on a functional epithelium and proper turnover of intestinal cells, supported by mitochondrial health. Mitochondria and lysosomes play key roles in cellular balance. Our previous researches indicate that biogenic selenium nanoparticles (SeNPs) can alleviate intestinal epithelial barrier damage by enhancing mitochondria-lysosome crosstalk, though the detailed mechanism is unclear. This study aimed to investigate the role of mitochondria-lysosome crosstalk in the protective effect of SeNPs on intestinal barrier function in mice exposed to lipopolysaccharide (LPS). The results showed that LPS exposure increased intestinal permeability in mice, leding to structural and functional damage to mitochondrial and lysosomal. Oral administration of SeNPs significantly upregulated the expression levels of TBC1D15 and Fis1, downregulated the expression levels of Rab7, Caspase-3, Cathepsin B, and MCOLN2, effectively alleviated LPS-induced mitochondrial and lysosomal dysfunction and maintained the intestinal barrier integrity in mice. Furthermore, SeNPs notably inhibited mitophagy caused by adenovirus-associated virus (AAV)-mediated RNA interference the expression of TBC1D15 in the intestine of mice, maintained mitochondrial and lysosomal homeostasis, and effectively alleviated intestinal barrier damage. These results suggested that SeNPs can regulate mitochondria-lysosome crosstalk and inhibit its damage by regulating the TBC1D15/Fis1/Rab7- signaling pathway. thereby alleviating intestinal barrier damage. It lays a theoretical foundation for elucidating the mechanism of mitochondria-lysosome crosstalk in regulating intestinal barrier damage and repair, and provides new ideas and new ways to establish safe and efficient nutritional regulation strategies to prevent and treat intestinal diseases caused by inflammation.
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Proteínas Activadoras de GTPasa , Mucosa Intestinal , Lisosomas , Mitocondrias , Proteínas Mitocondriales , Nanopartículas , Selenio , Transducción de Señal , Proteínas de Unión al GTP rab , Proteínas de Unión a GTP rab7 , Animales , Selenio/farmacología , Nanopartículas/química , Ratones , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Activadoras de GTPasa/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Masculino , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas de la Membrana/metabolismo , Lipopolisacáridos , Ratones Endogámicos C57BL , Permeabilidad/efectos de los fármacosRESUMEN
Mitochondrial dysfunction is the leading cause of neurodegenerative disorders like Alzheimer's disease and Parkinson's disease. Mitochondria is a highly dynamic organelle continuously undergoing the process of fission and fusion for even distribution of components and maintaining proper shape, number, and bioenergetic functionality. A set of genes governs the process of fission and fusion. OPA1, Mfn1, and Mfn2 govern fusion, while Drp1, Fis1, MIEF1, and MIEF2 genes control fission. Determination of specific molecular patterns of transcripts of these genes revealed the impact of compositional constraints on selecting optimal codons. AGA and CCA codons were over-represented, and CCC, GTC, TTC, GGG, ACG were under-represented in the fusion gene set. In contrast, CTG was over-represented, and GCG, CCG, and TCG were under-represented in the fission gene set. Hydropathicity analysis revealed non-polar protein products of both fission and fusion gene set transcripts. AGA codon repeats are an integral part of translational regulation machinery and present a distinct pattern of over-representation and under-representation in different transcripts within the gene sets, suggestive of selective translational force precisely controlling the occurrence of the codon. Out of six synonymous codons, five synonymous codons encoding for leucine were used differently in both gene sets. Hence, forces regulating the occurrence of AGA and five synonymous leucine-encoding codons suggest translational selection. A correlation of mutational bias with gene expression and codon bias and GRAVY and AROMA signifies the selection pressure in both gene sets, while the correlation of compositional bias with gene expression, codon bias, protein properties, and minimum free energy signifies the presence of compositional constraints. More than 25% of codons of both gene sets showed a significant difference in codon usage. The overall analysis shed light on molecular features of gene sets involved in fission and fusion.
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BACKGROUND: Acute kidney injury (AKI) is a common clinical disorder with complex etiology and poor prognosis, and currently lacks specific and effective treatment options. Mitochondrial dynamics dysfunction is a prominent feature in AKI, and modulation of mitochondrial morphology may serve as a potential therapeutic approach for AKI. METHODS: We induced ischemia-reperfusion injury (IRI) in mice (bilateral) and Bama pigs (unilateral) by occluding the renal arteries. ATP depletion and recovery (ATP-DR) was performed on proximal renal tubular cells to simulate in vitro IRI. Renal function was evaluated using creatinine and urea nitrogen levels, while renal structural damage was assessed through histopathological staining. The role of Drp1 was investigated using immunoblotting, immunohistochemistry, immunofluorescence, and immunoprecipitation techniques. Mitochondrial morphology was evaluated using confocal microscopy. RESULTS: Renal IRI induced significant mitochondrial fragmentation, accompanied by Dynamin-related protein 1 (Drp1) translocation to the mitochondria and Drp1 phosphorylation at Ser616 in the early stages (30 min after reperfusion), when there was no apparent structural damage to the kidney. The use of the Drp1 inhibitor P110 significantly improved kidney function and structural damage. P110 reduced Drp1 mitochondrial translocation, disrupted the interaction between Drp1 and Fis1, without affecting the binding of Drp1 to other mitochondrial receptors such as MFF and Mid51. High-dose administration had no apparent toxic side effects. Furthermore, ATP-DR induced mitochondrial fission in renal tubular cells, accompanied by a decrease in mitochondrial membrane potential and an increase in the translocation of the pro-apoptotic protein Bax. This process facilitated the release of dsDNA, triggering the activation of the cGAS-STING pathway and promoting inflammation. P110 attenuated mitochondrial fission, suppressed Bax mitochondrial translocation, prevented dsDNA release, and reduced the activation of the cGAS-STING pathway. Furthermore, these protective effects of P110 were also observed renal IRI model in the Bama pig and folic acid-induced nephropathy in mice. CONCLUSIONS: Dysfunction of mitochondrial dynamics mediated by Drp1 contributes to renal IRI. The specific inhibitor of Drp1, P110, demonstrated protective effects in both in vivo and in vitro models of AKI.
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Lesión Renal Aguda , Animales , Ratones , Porcinos , Proteína X Asociada a bcl-2 , Dinaminas , Nucleotidiltransferasas , Adenosina TrifosfatoRESUMEN
METTL3, an RNA methyltransferase enzyme, exerts therapeutic effects on various cardiovascular diseases. Myocardial ischemia-reperfusion injury (MIRI) and subsequently cardiac fibrosis is linked to acute cardiomyocyte death or dysfunction induced by mitochondrial damage, particularly mitochondrial fission. Our research aims to elucidate the potential mechanisms underlying the therapeutic actions of METTL3 in MIRI, with focus on mitochondrial fission. When compared with Mettl3flox mice subjected to MIRI, Mettl3 cardiomyocyte knockout (Mettl3Cko) mice have reduced infarct size, decreased serum levels of myocardial injury-related factors, limited cardiac fibrosis, and preserved myocardial ultrastructure and contractile/relaxation capacity. The cardioprotective actions of Mettl3 knockout were associated with reduced inflammatory responses, decreased myocardial neutrophil infiltration, and suppression of cardiomyocyte death. Through signaling pathway validation experiments and assays in cultured HL-1 cardiomyocytes exposed to hypoxia/reoxygenation, we confirmed that Mettl3 deficiency interfere with DNA-PKcs phosphorylation, thereby blocking the downstream activation of Fis1 and preventing pathological mitochondrial fission. In conclusion, this study confirms that inhibition of METTL3 can alleviate myocardial cardiac fibrosis inflammation and prevent cardiomyocyte death under reperfusion injury conditions by disrupting DNA-PKcs/Fis1-dependent mitochondrial fission, ultimately improving cardiac function. These findings suggest new approaches for clinical intervention in patients with MIRI.
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Dinámicas Mitocondriales , Daño por Reperfusión Miocárdica , Animales , Humanos , Ratones , Apoptosis , ADN/metabolismo , Fibrosis , Isquemia/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismoRESUMEN
In genetically heterogeneous (UM-HET3) mice produced by the CByB6F1 × C3D2F1 cross, the Nrf2 activator astaxanthin (Asta) extended the median male lifespan by 12% (p = 0.003, log-rank test), while meclizine (Mec), an mTORC1 inhibitor, extended the male lifespan by 8% (p = 0.03). Asta was fed at 1840 ± 520 (9) ppm and Mec at 544 ± 48 (9) ppm, stated as mean ± SE (n) of independent diet preparations. Both were started at 12 months of age. The 90th percentile lifespan for both treatments was extended in absolute value by 6% in males, but neither was significant by the Wang-Allison test. Five other new agents were also tested as follows: fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate. None of these increased lifespan significantly at the dose and method of administration tested in either sex. Amounts of dimethyl fumarate in the diet averaged 35% of the target dose, which may explain the absence of lifespan effects. Body weight was not significantly affected in males by any of the test agents. Late life weights were lower in females fed Asta and Mec, but lifespan was not significantly affected in these females. The male-specific lifespan benefits from Asta and Mec may provide insights into sex-specific aspects of aging.
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Flavonoles , Sulfuro de Hidrógeno , Longevidad , Fenilbutiratos , Femenino , Ratones , Masculino , Animales , Meclizina/farmacología , Sulfuro de Hidrógeno/farmacología , Dimetilfumarato/farmacología , Ácido Micofenólico/farmacología , XantófilasRESUMEN
Myxococcus xanthus and Escherichia coli represent a well-studied microbial predator-prey pair frequently examined in laboratory settings. While significant progress has been made in comprehending the mechanisms governing M. xanthus predation, various aspects of the response and defensive mechanisms of E. coli as prey remain elusive. In this study, the E. coli MG1655 large-scale chromosome deletion library was screened, and a mutant designated as ME5012 was identified to possess significantly reduced susceptibility to predation by M. xanthus. Within the deleted region of ME5012 encompassing seven genes, the significance of dusB and fis genes in driving the observed phenotype became apparent. Specifically, the deletion of fis resulted in a notable reduction in flagellum production in E. coli, contributing to a certain level of resistance against predation by M. xanthus. Meanwhile, the removal of dusB in E. coli led to diminished inducibility of myxovirescin A production by M. xanthus, accompanied by a slight decrease in susceptibility to myxovirescin A. These findings shed light on the molecular mechanisms underlying the complex interaction between M. xanthus and E. coli in a predatory context.
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In critical care patients, the ""temporary inactivity of the diaphragm caused by mechanical ventilation (MV) triggers a series of events leading to diaphragmatic dysfunction and atrophy, commonly known as ventilator-induced diaphragm dysfunction (VIDD). While mitochondrial dysfunction related to oxidative stress is recognized as a crucial factor in VIDD, the exact molecular mechanism remains poorly understood. In this study, we observe that 6â h of MV triggers aberrant mitochondrial dynamics, resulting in a reduction in mitochondrial size and interaction, associated with increased expression of dynamin-related protein 1 (DRP1). This effect can be prevented by P110, a molecule that inhibits the recruitment of DRP1 to the mitochondrial membrane. Furthermore, isolated mitochondria from the diaphragms of ventilated patients exhibited increased production of reactive oxygen species (ROS). These mitochondrial changes were associated with the rapid oxidation of type 1 ryanodine receptor (RyR1) and a decrease in the stabilizing subunit calstabin 1. Subsequently, we observed that the sarcoplasmic reticulum (SR) in the ventilated diaphragms showed increased calcium leakage and reduced contractile function. Importantly, the mitochondrial fission inhibitor P110 effectively prevented all of these alterations. Taken together, the results of our study illustrate that MV leads, in the diaphragm, to both mitochondrial fragmentation and dysfunction, linked to the up-/down-regulation of 320 proteins, as assessed through global comprehensive quantitative proteomics analysis, primarily associated with mitochondrial function. These outcomes underscore the significance of developing compounds aimed at modulating the balance between mitochondrial fission and fusion as potential interventions to mitigate VIDD in human patients.
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Mobile genetic elements (MGEs) are relevant agents in bacterial adaptation and evolutionary diversification. Stable appropriation of these DNA elements depends on host factors, among which are the nucleoid-associated proteins (NAPs). NAPs are highly abundant proteins that bind and bend DNA, altering its topology and folding, thus affecting all known cellular DNA processes from replication to expression. Even though NAP coding genes are found in most prokaryotic genomes, their functions in host chromosome biology and xenogeneic silencing are only known for a few NAP families. Less is known about the occurrence, abundance, and roles of MGE-encoded NAPs in foreign elements establishment and mobility. In this study, we used a combination of comparative genomics and phylogenetic strategies to gain insights into the diversity, distribution, and functional roles of NAPs within the class Acidithiobacillia with a special focus on their role in MGE biology. Acidithiobacillia class members are aerobic, chemolithoautotrophic, acidophilic sulfur-oxidizers, encompassing substantial genotypic diversity attributable to MGEs. Our search for NAP protein families (PFs) in more than 90 genomes of the different species that conform the class, revealed the presence of 1,197 proteins pertaining to 12 different NAP families, with differential occurrence and conservation across species. Pangenome-level analysis revealed 6 core NAP PFs that were highly conserved across the class, some of which also existed as variant forms of scattered occurrence, in addition to NAPs of taxa-restricted distribution. Core NAPs identified are reckoned as essential based on the conservation of genomic context and phylogenetic signals. In turn, various highly diversified NAPs pertaining to the flexible gene complement of the class, were found to be encoded in known plasmids or, larger integrated MGEs or, present in genomic loci associated with MGE-hallmark genes, pointing to their role in the stabilization/maintenance of these elements in strains and species with larger genomes. Both core and flexible NAPs identified proved valuable as markers, the former accurately recapitulating the phylogeny of the class, and the later, as seed in the bioinformatic identification of novel episomal and integrated mobile elements.
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The Internet of Things (IoT) is an advanced technology that comprises numerous devices with carrying sensors to collect, send, and receive data. Due to its vast popularity and efficiency, it is employed in collecting crucial data for the health sector. As the sensors generate huge amounts of data, it is better for the data to be aggregated before being transmitting the data further. These sensors generate redundant data frequently and transmit the same values again and again unless there is no variation in the data. The base scheme has no mechanism to comprehend duplicate data. This problem has a negative effect on the performance of heterogeneous networks.It increases energy consumption; and requires high control overhead, and additional transmission slots are required to send data. To address the above-mentioned challenges posed by duplicate data in the IoT-based health sector, this paper presents a fuzzy data aggregation system (FDAS) that aggregates data proficiently and reduces the same range of normal data sizes to increase network performance and decrease energy consumption. The appropriate parent node is selected by implementing fuzzy logic, considering important input parameters that are crucial from the parent node selection perspective and share Boolean digit 0 for the redundant values to store in a repository for future use. This increases the network lifespan by reducing the energy consumption of sensors in heterogeneous environments. Therefore, when the complexity of the environment surges, the efficiency of FDAS remains stable. The performance of the proposed scheme has been validated using the network simulator and compared with base schemes. According to the findings, the proposed technique (FDAS) dominates in terms of reducing energy consumption in both phases, achieves better aggregation, reduces control overhead, and requires the fewest transmission slots.
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Purpose: (1) To evaluate if energy availability (EA), macronutrient intake and body composition change over four training periods in young, highly trained, female cross-country skiers, and (2) to clarify if EA, macronutrient intake, body composition, and competition performance are associated with each other in this cohort. Methods: During a one-year observational study, 25 female skiers completed 3-day food and training logs during four training periods: preparation, specific preparation, competition, and transition periods. A body composition measurement (bioimpedance analyzer) was performed at the end of the preparation, specific preparation, and competition periods. Competition performance was determined by International Ski Federation (FIS) points gathered from youth national championships. Results: EA (36-40â kcal·kg FFM-1·d-1) and carbohydrate (CHO) intake (4.4-5.1â g·kg-1·d-1) remained similar, and at a suboptimal level, between training periods despite a decrease in exercise energy expenditure (p = 0.002) in the transition period. Higher EA (r = -0.47, p = 0.035) and CHO intake (r = -0.65, p = 0.002) as well as lower FM (r = 0.60, p = 0.006) and F% (r = 0.57, p = 0.011) were associated with lower (better) FIS-points. CHO intake was the best predictor of distance competition performance (R2 = 0.46, p = 0.004). Conclusions: Young female cross-country skiers had similar EA and CHO intake over four training periods. Both EA and CHO intake were at suboptimal levels for performance and recovery. CHO intake and body composition are important factors influencing competition performance in young female cross-country skiers.
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Mitochondria, which generate ATP through aerobic respiration, also have important noncanonical functions. Mitochondria are dynamic organelles, that engage in fission (division), fusion (joining) and translocation. They also regulate intracellular calcium homeostasis, serve as oxygen-sensors, regulate inflammation, participate in cellular and organellar quality control and regulate the cell cycle. Mitochondrial fission is mediated by the large GTPase, dynamin-related protein 1 (Drp1) which, when activated, translocates to the outer mitochondrial membrane (OMM) where it interacts with binding proteins (Fis1, MFF, MiD49 and MiD51). At a site demarcated by the endoplasmic reticulum, fission proteins create a macromolecular ring that divides the organelle. The functional consequence of fission is contextual. Physiological fission in healthy, nonproliferating cells mediates organellar quality control, eliminating dysfunctional portions of the mitochondria via mitophagy. Pathological fission in somatic cells generates reactive oxygen species and triggers cell death. In dividing cells, Drp1-mediated mitotic fission is critical to cell cycle progression, ensuring that daughter cells receive equitable distribution of mitochondria. Mitochondrial fusion is regulated by the large GTPases mitofusin-1 (Mfn1) and mitofusin-2 (Mfn2), which fuse the OMM, and optic atrophy 1 (OPA-1), which fuses the inner mitochondrial membrane. Mitochondrial fusion mediates complementation, an important mitochondrial quality control mechanism. Fusion also favors oxidative metabolism, intracellular calcium homeostasis and inhibits cell proliferation. Mitochondrial lipids, cardiolipin and phosphatidic acid, also regulate fission and fusion, respectively. Here we review the role of mitochondrial dynamics in health and disease and discuss emerging concepts in the field, such as the role of central versus peripheral fission and the potential role of dynamin 2 (DNM2) as a fission mediator. In hyperproliferative diseases, such as pulmonary arterial hypertension and cancer, Drp1 and its binding partners are upregulated and activated, positing mitochondrial fission as an emerging therapeutic target.
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Neoplasias , Hipertensión Arterial Pulmonar , Humanos , Dinámicas Mitocondriales/fisiología , Calcio , Dinaminas/metabolismo , GTP Fosfohidrolasas/metabolismo , Ciclo CelularRESUMEN
This review summarizes current knowledge about the mechanisms of timely binding and dissociation of two nucleoid proteins, IHF and Fis, which play fundamental roles in the initiation of chromosomal DNA replication in Escherichia coli. Replication is initiated from a unique replication origin called oriC and is tightly regulated so that it occurs only once per cell cycle. The timing of replication initiation at oriC is rigidly controlled by the timely binding of the initiator protein DnaA and IHF to oriC. The first part of this review presents up-to-date knowledge about the timely stabilization of oriC-IHF binding at oriC during replication initiation. Recent advances in our understanding of the genome-wide profile of cell cycle-coordinated IHF binding have revealed the oriC-specific stabilization of IHF binding by ATP-DnaA oligomers at oriC and by an initiation-specific IHF binding consensus sequence at oriC. The second part of this review summarizes the mechanism of the timely regulation of DnaA activity via the chromosomal loci DARS2 (DnaA-reactivating sequence 2) and datA. The timing of replication initiation at oriC is controlled predominantly by the phosphorylated form of the adenosine nucleotide bound to DnaA, i.e., ATP-DnaA, but not ADP-ADP, is competent for initiation. Before initiation, DARS2 increases the level of ATP-DnaA by stimulating the exchange of ADP for ATP on DnaA. This DARS2 function is activated by the site-specific and timely binding of both IHF and Fis within DARS2. After initiation, another chromosomal locus, datA, which inactivates ATP-DnaA by stimulating ATP hydrolysis, is activated by the timely binding of IHF. A recent study has shown that ATP-DnaA oligomers formed at DARS2-Fis binding sites competitively dissociate Fis via negative feedback, whereas IHF regulation at DARS2 and datA still remains to be investigated. This review summarizes the current knowledge about the specific role of IHF and Fis in the regulation of replication initiation and proposes a mechanism for the regulation of timely IHF binding and dissociation at DARS2 and datA.
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Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Factores de Integración del Huésped/genética , Factores de Integración del Huésped/metabolismo , Origen de Réplica , Replicación del ADN , Ciclo Celular , Adenosina Trifosfato/metabolismo , ADN Bacteriano/genética , Factor Proteico para Inverción de Estimulación/genética , Factor Proteico para Inverción de Estimulación/metabolismoRESUMEN
Mitochondrial dynamics plays a significant role in shaping the mitochondrial network and maintaining mitochondrial function. Imbalanced mitochondrial dynamics can cause mitochondrial dysfunction leading to a wide range of diseases/disorders. The aim of this study was to investigate the expression of mitochondrial dynamics markers and regulatory molecules in whole adrenal glands, cortices, and medullae obtained from adult male rats exposed to acute and repeated psychophysical stress, the most common stress in human society. The transcriptional profiles of most of the mitochondrial dynamics markers investigated here were altered: 81%-(17/21) in the whole adrenal gland, 76.2%-(16/21) in the adrenal cortex, and 85.7%-(18/21) in the adrenal medulla. Changes were evident in representatives of every process of mitochondrial dynamics. Markers of mitobiogenesis were changed up to 62.5%-(5/8) in the whole adrenal gland, 62.5%-(5/8) in the adrenal cortex, and 87.5%-(7/8) in the adrenal medulla. Markers of mitofusion were changed up to 100%-(3/3) in the whole adrenal gland, 66.7%-(5/8) in the adrenal cortex, and 87.5%-(7/8) in the adrenal medulla, while all markers of mitofission and mitophagy were changed in the adrenal glands. Moreover, almost all markers of mitochondrial functionality were changed: 83.3%-(5/6) in the whole adrenal, 83.3%-(5/6) in the cortex, 66.7%-(4/6) in the medulla. Accordingly, the study highlights the significant impact of acute and repeated stress on mitochondrial dynamics in the adrenal gland.
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PURPOSE: To determine whether competitive performance, as defined by International Biathlon Union (IBU) and International Ski Federation (FIS) points in biathlon and cross-country (XC) skiing, respectively, can be projected using a combination of anthropometric and physiological metrics. Shooting accuracy was also included in the biathlon models. METHODS: Data were analyzed using multivariate methods from 45 (23 female and 22 male) biathletes and 202 (86 female and 116 male) XC skiers who were all members of senior national teams, national development teams, or ski-university or high school invite-only programs (age range: 16-36 y). Anthropometric and physiological characteristics were assessed via dual-energy X-ray absorptiometry and incremental roller-ski treadmill tests, respectively. Shooting accuracy was assessed via an outdoor standardized testing protocol. RESULTS: Valid projective models were identified for female biathletes' IBU points (R2 = .80/Q2 = .65) and female XC skiers' FIS distance (R2 = .81/Q2 = .74) and sprint (R2 = .81/Q2 = .70) points. No valid models were identified for the men. The most important variables for the projection of IBU points were shooting accuracy, speeds at blood lactate concentrations of 4 and 2 mmol·L-1, peak aerobic power, and lean mass. The most important variables for the projection of FIS distance and sprint points were speeds at blood lactate concentrations of 4 and 2 mmol·L-1 and peak aerobic power. CONCLUSIONS: This study highlights the relative importance of specific anthropometric, physiological, and shooting-accuracy metrics in female biathletes and XC skiers. The data can help to identify the specific metrics that should be targeted when monitoring athletes' progression and designing training plans.
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Rendimiento Atlético , Esquí , Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Esquí/fisiología , Prueba de Esfuerzo , Antropometría , Atletas , Ácido Láctico , Rendimiento Atlético/fisiología , Consumo de OxígenoRESUMEN
Endosperm is a key nutritive tissue that supports the developing embryo or seedling, and serves as a major nutritional source for human and livestock feed. In sexually-reproducing flowering plants, it generally develops after fertilization. However, autonomous endosperm (AE) formation (i.e. independent of fertilization) is also possible. Recent findings of AE loci/ genes and aberrant imprinting in native apomicts, together with a successful initiation of parthenogenesis in rice and lettuce, have enhanced our understanding of the mechanisms bridging sexual and apomictic seed formation. However, the mechanisms driving AE development are not well understood. This review presents novel aspects related to AE development in sexual and asexual plants underlying stress conditions as the primary trigger for AE. Both application of hormones to unfertilized ovules and mutations that impair epigenetic regulation lead to AE development in sexual Arabidopsis thaliana, which may point to a common pathway for both phenomena. Apomictic-like AE development under experimental conditions can take place due to auxin-dependent gene expression and/or DNA methylation.