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Biotic and abiotic stresses frequently co-occur in nature, yet relatively little is known about how plants co-ordinate the response to combined stresses. Protein degradation by the ubiquitin/proteasome system is central to the regulation of multiple independent stress response pathways in plants. The Arg/N-degron pathway is a subset of the ubiquitin/proteasome system that targets proteins based on their N termini and has been specifically implicated in the responses to biotic and abiotic stresses, including hypoxia, via accumulation of group VII ETHYLENE RESPONSE FACTOR (ERF-VII) transcription factors that orchestrate the onset of the hypoxia response program. Here, we investigated the role of the Arabidopsis (Arabidopsis thaliana) Arg/N-degron pathway in mediating the crosstalk between combined abiotic and biotic stresses using hypoxia treatments and the flg22 elicitor of pattern-triggered immunity (PTI), respectively. We uncovered a link between the plant transcriptional responses to hypoxia and flg22. Combined hypoxia and flg22 treatments showed that hypoxia represses the flg22 transcriptional program, as well as the expression of pattern recognition receptors, mitogen-activated protein kinase (MAPK) signalling and callose deposition during PTI through mechanisms that are mostly independent from the ERF-VIIs. These findings improve our understanding of the trade-offs between plant responses to combined abiotic and biotic stresses in the context of our efforts to increase crop resilience to global climate change. Our results also show that the well-known repressive effect of hypoxia on innate immunity in animals also applies to plants.
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Chemical communication through olfaction is crucial for fish behaviours, mediating in socio-sexual behaviours as reproduction. Turbot, a flatfish with significant aquaculture production, possesses a well-developed olfactory system from early developmental stages. After metamorphosis, flatfish acquire their characteristic bilateral asymmetry with an ocular side facing the open water column, housing the dorsal olfactory rosette, and a blind side in contact with the sea bottom where the ventral rosette is located. This study aimed to address the existing gap in specific histological, ultrastructural, lectin-histochemical and immunohistochemical studies of the turbot olfactory rosettes and olfactory bulbs. We examined microdissected olfactory organs of adult turbots and premetamorphic larvae by using routine histological staining techniques, and a wide array of lectins and primary antibodies against G-proteins and calcium-binding proteins. We observed no discernible structural variations in the olfactory epithelium between rosettes, except for the dorsal rosette being larger in size compared to the ventral rosette. Additionally, the use of transmission electron microscopy significantly improved the characterization of the adult olfactory epithelium, exhibiting high cell density, small cell size, and a wide diversity of cell types. Moreover, specific immunopositivity in sensory and non-sensory cells provided us of essential information regarding their olfactory roles. The results obtained significantly enriched the scarce morphological and neurochemical information available on the turbot olfactory system, revealing a highly complex olfactory epithelium with distinct features compared to other teleost species, especially with regard to olfactory cell distribution and immunolabelling patterns.
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Annually, 8.3 million tonnes of mismanaged plastic waste enter oceans, prompting the food packaging industry, a major contributor, to minimize its environmental footprint. Within the seafood sector, a nascent number of studies are exploring the impacts of various packaging solutions for distribution, yet clear insights remain elusive. This study tries to fill the gap by comparing the impacts of two seafood packaging options: disposable expandable polystyrene (EPS) boxes and, for the first time, reusable plastic crates (RPC) crafted from high-density polyethylene. Using the life cycle assessment methodology with a 'cradle to grave' approach, the research evaluates the distribution of 1260,000 t of fish from port of Vigo (Spain) to various markets. Similar climate change values emerge in local (5.00·107 kg CO2 eq.) and regional trade (1.20·108 kg CO2 eq.) for both options, but RPCs exhibit around a 12 % increase (6.15·108 kg CO2 eq.) during national distribution, emphasizing package weight and load significance. The findings across all impact categories exhibited general consistent trends. The sensitivity analysis suggests relocating washing facilities to port could enhance RPCs´ environmental benefits for transport within a 160 km range. These findings underscore reusable packaging's potential as an eco-friendlier alternative in specific contexts, aligning with heightened environmental concerns and regulatory pressures surrounding plastic usage.
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We aimed to qualitatively and quantitatively analyze, through a systematic review and meta-analysis, the current evidence on the differential expression of the hallmarks of cancer in oral lichen planus (OLP) samples, in order to know the earliest molecular mechanisms that could be involved in the malignant transformation of this oral potentially malignant disorder. We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2023. We evaluated the methodological quality of studies and carried out meta-analyses to fulfill our objectives. Inclusion criteria were met by 110 primary-level studies, with 7065 OLP samples, in which the expression of 104 biomarkers were analyzed through immunohistochemistry. Most OLP samples showed sustained cell proliferation signaling (65.48%, 95%CI = 51.87-78.02), anti-apoptotic pathways (55.93%, 95%CI = 35.99-75.0), genome instability (48.44%, 95%CI = 13.54-84.19), and tumor-promoting inflammation events (83.10%, 95%CI = 73.93-90.74). Concurrently, OLP samples also harbored tumor growth suppressor mechanisms (64.00%, 95%CI = 53.27-74.12). In conclusion, current evidence indicates that molecular mechanisms promoting hyperproliferative signaling, an antiapoptotic state with genomic instability, and an escape of epithelial cells from immune destruction, are developed in LP-affected oral mucosa. It is plausible that these events are due to the actions exerted by the chronic inflammatory infiltrate. Malignant transformation appears to be prevented by tumor suppressor genes, which showed consistent upregulation in OLP samples.
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Organic acids (OAs) are employed in animal feed to regulate gastrointestinal disorders and diarrhoea thanks to their ability to modulate the gastrointestinal environment and their antimicrobial capacity. However, there is not enough evidence regarding the most adequate OA and its effectiveness in rabbit farming. Therefore, the aim of this study was to screen and evaluate the response of young rabbits to six OAs, administered via drinking water, at three different concentrations (pH levels). Organic acids (acetic, ACET; formic, FOR; propionic, PROP; lactic, LAC; citric, CIT; and butyric, BUT) were tested at three concentrations (pH 3, 4, and 5). A negative control (CON; non-acidified water) was also included. We used 240 weaned rabbits (28 days old) divided into 2 batches. In each batch, animals were randomly allocated to 1 of the 19 experimental treatments and were housed in group cages of 6 animals per cage, treatment, and batch. Among the 240 rabbits, an additional cage with 6 animals was included to determine the initial physiological state of the animals. All animals were fed with commercial pelleted feed throughout the whole experiment. The duration of the study was 7 days, until 35 days of age. At 31 and 35 days of age, in each batch, three animals per day and treatment were slaughtered. The pH of the digestive contents in the fundus, antrum, duodenum, jejunum, ileum, and cecum, as well as the gastric pepsin enzyme activity, was measured. Water and feed consumption per cage and individual body weight (BW) were recorded daily. The type and dosage of OAs affected water intake. ACET 3, PROP 3, and BUT 3 reduced water intake compared to CON, negatively impacting feed intake and weight gain. FOR and CIT acids led to the highest BW and weight gain at 35 days, compared to PROP, LAC, and BUT (p < 0.05); showing ACET intermediate values. While OAs had limited effects on gastric and small intestine pH, acidified water at pH 4 and 5 lowered ileum and caecum pH (p < 0.05) compared to pH 3. Acidified water at pH 4 showed the highest (p < 0.05) pepsin activity compared to pH 3 and pH 5. Considering the limited sample size and short-term assessment period of our screening test, the OAs with the highest potential for use in post-weaning rabbits were FOR, ACET, and CIT at pH 4. The selected combinations did not exhibit any early adverse effects in young rabbits. These results should be further confirmed in a broader population of animals. It would also be advisable to extend the application of OAs over longer periods to evaluate their effects throughout the entire growing period of rabbits.
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Myostatin is a growth factor related to muscular mass atrophy via mTOR pathway inhibition. Mutations in this gene have been correlated with high muscular mass development in different species of mammals, including human and dogs. Different studies have shown that sport practice increases myostatin gene expression. Some of them were conducted in canine breeds selected for different sport practices, including mushing sports. In this study, body weight, muscular mass, and serum levels of myostatin were analysed in different canine breeds, selected, and not selected for sprint and middle-distance racing, and the effect on epidemiological factors was evaluated. Sex, reproductive status, and canine breed affects body weight and muscular mass, being higher in males, and in sled canine breed. Age has an effect in body weight and myostatin serum levels, being lower in elder dogs. Sport practice and type of diet had an effect in muscular mass development but not in myostatin serum levels. Results showed a high positive correlation between muscular mass and body weight but not with myostatin levels. These results suggest that independent-myostatin mechanisms of mTOR pathway regulation could be related to muscular mass development in dogs.
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OBJECTIVE: To evaluate cognitive function in patients with rheumatoid arthritis (RA) and inflammatory activity. PATIENTS AND METHODS: We performed a cross-sectional study of a cohort of patients with RA initiating their first biological treatment due to moderate-to-high inflammation and a healthy control group (no inflammatory diseases) matched for age, sex and educational level. All participants underwent a comprehensive neuropsychological assessment, with cognitive impairment defined as a Montreal Cognitive Assessment (MoCA) score<26. Additional assessments included various cognitive tests (STROOP, forward and backward digit spans), anxiety and depression scales (Hospital Anxiety and Depression Scale), quality of life measures (Quality of Life-Rheumatoid Arthritis) and average inflammatory activity according to the 28-joint Disease Activity Score (DAS28)-C-reactive protein (CRP) into high activity (DAS28≥3.2) and low activity (DAS28<3.2) groups, also CRP levels and interleukin 6 (IL-6) levels were measured using an ELISA. RESULTS: The study population comprised 140 participants, 70 patients with RA and 70 controls. Patients more frequently experienced cognitive impairment than controls (60% vs 40%; p=0.019) and had lower mean (SD) values in the MoCA (23.6 (3.9) vs 25.1 (3.4); p=0.019. As for subtests of the MoCA, involvement was more marked in patients than in controls for the visuospatial-executive (p=0.030), memory (p=0.026) and abstraction (p=0.039) domains. Additionally, patients scored lower on executive function, as assessed by the backward digit span test (4.0 (1.7) vs 4.7 (1.9); p=0.039). Cognitive impairment is associated with age and a lower educational level in the general population, and among patients with RA with educational level, obesity and average inflammatory activity (DAS28, CRP, and IL-6). CONCLUSIONS: Patients with RA with high inflammatory activity are more susceptible to cognitive impairment, which specifically affects the domains of visuospatial, memory, abstraction and executive function.
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Artrite Reumatoide , Proteína C-Reativa , Cognição , Disfunção Cognitiva , Inflamação , Testes Neuropsicológicos , Humanos , Artrite Reumatoide/psicologia , Artrite Reumatoide/complicações , Artrite Reumatoide/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Inflamação/sangue , Inflamação/etiologia , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico , Idoso , Qualidade de Vida , Biomarcadores/sangue , Índice de Gravidade de Doença , Estudos de Casos e Controles , Interleucina-6/sangue , AdultoRESUMO
Starch utilization system (Sus)D-homologs are well known for their carbohydrate-binding capabilities and are part of the sus operon in microorganisms affiliated with the phylum Bacteroidota. Until now, SusD-like proteins have been characterized regarding their affinity toward natural polymers. In this study, three metagenomic SusD homologs (designated SusD1, SusD38489, and SusD70111) were identified and tested with respect to binding to natural and non-natural polymers. SusD1 and SusD38489 are cellulose-binding modules, while SusD70111 preferentially binds chitin. Employing translational fusion proteins with superfolder GFP (sfGFP), pull-down assays, and surface plasmon resonance (SPR) has provided evidence for binding to polyethylene terephthalate (PET) and other synthetic polymers. Structural analysis suggested that a Trp triad might be involved in protein adsorption. Mutation of these residues to Ala resulted in an impaired adsorption to microcrystalline cellulose (MC), but not so to PET and other synthetic polymers. We believe that the characterized SusDs, alongside the methods and considerations presented in this work, will aid further research regarding bioremediation of plastics. IMPORTANCE: SusD1 and SusD38489 can be considered for further applications regarding their putative adsorption toward fossil-fuel based polymers. This is the first time that SusD homologs from the polysaccharide utilization loci (PUL), largely described for the phylum Bacteroidota, are characterized as synthetic polymer-binding proteins.
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Proteínas de Bactérias , Bacteroidetes , Metagenoma , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Bacteroidetes/genética , Bacteroidetes/metabolismo , Celulose/metabolismo , Polímeros/metabolismo , Quitina/metabolismo , Polietilenotereftalatos/metabolismoRESUMO
A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). The study analysed articles published in JCR journals from 2019 to 2024. The search strategy comprised the MESH, free terms of "Neuroinflammation", and selective searches for the following single biomarkers that had previously been selected from the relevant literature: "High mobility group box 1/HMGB1", "Toll-Like-Receptor 4/TLR-4", "Interleukin-1/IL-1", "Interleukin-6/IL-6", "Transforming growth factor beta/TGF-ß", and "Tumour necrosis factor-alpha/TNF-α". These queries were all combined with the MESH terms "Epileptogenesis" and "Epilepsy". We found 243 articles related to epileptogenesis and neuroinflammation, with 356 articles from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 55 evaluated by the authors. A total of 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. As conclusion, this systematic review provides acceptable support for five biomarkers, including TNF-α and some of its soluble receptors (sTNFr2), HMGB1, TLR-4, CCL2 and IL-33. Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control of epileptic seizures. Their value will be better defined by future studies.
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Biomarcadores , Proteína HMGB1 , Doenças Neuroinflamatórias , Humanos , Doenças Neuroinflamatórias/diagnóstico , Doenças Neuroinflamatórias/metabolismo , Proteína HMGB1/metabolismo , Epilepsia/diagnóstico , Epilepsia/metabolismo , Citocinas/metabolismo , Receptor 4 Toll-Like/metabolismo , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/metabolismoRESUMO
Dogs are considered the main reservoir of several zoonoses endemic to the Mediterranean Basin. In this study, a prevalence of infections and coinfections of canine vector-borne diseases was analyzed in apparently healthy dogs of different canine pure breeds in Sicily (Italy), where these diseases are endemic. The seroprevalence of Leishmania infantum, Ricketsia ricketsii, Anaplasma phagocytophilum, and Erlichia canis was assessed, as single and coinfections. Biochemical and hematological parameters were evaluated, and epidemiological factors, including sex, age, and canine breed, were recovered. The most frequent infection was L. infantum (45.61%), following R. ricketsii (36.84%), both as single, double, or triple coinfections. Coinfections change the biochemical and hematological parameters of the host, and canine breeds are related to the infection frequency and the parameters observed during infections. Changes in the complete blood count (CBC) and biochemical values also differ between canine breeds, with the Cirneco dell'Etna dogs infected with L. infantum being the animals presenting the most interesting results in our study. High values of RBC, hemoglobin, hematocrit, mean corpuscular hemoglobin (MCH), the albumin/globulin (A/G) ratio, and albumin and low levels of ß-2 globulin and γ-globulin were found only in this canine breed, suggesting some resistance to infection in these dogs. Future studies about the immune response of this canine breed could be interesting to determine their possible resistance to zoonotic pathogens, such as L. infantum.
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With the main aim of identifying biomarkers that contribute to defining the concept of ideal protein in growing rabbits under the most diverse conditions possible this work describes two different experiments. Experiment 1: 24 growing rabbits are included at 56 days of age. The rabbits are fed ad libitum one of the two experimental diets only differing in lysine levels. Experiment 2: 53 growing rabbits are included at 46 days of age, under a fasting and eating one of the five experimental diets, with identical chemical composition except for the three typically limiting amino acids (being fed commercial diets ad libitum in both experiments). Blood samples are taken for targeted and untargeted metabolomics analysis. Here we show that the metabolic phenotype undergoes alterations when animals experience a rapid dietary shift in the amino acid levels. While some of the differential metabolites can be attributed directly to changes in specific amino acids, creatinine, urea, hydroxypropionic acid and hydroxyoctadecadienoic acid are suggested as a biomarker of amino acid imbalances in growing rabbits' diets, since its changes are not attributable to a single amino acid. The fluctuations in their levels suggest intricate amino acid interactions. Consequently, we propose these metabolites as promising biomarkers for further research into the concept of the ideal protein using rabbit as a model.
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Aminoácidos , Ração Animal , Biomarcadores , Metabolômica , Animais , Coelhos , Biomarcadores/sangue , Biomarcadores/metabolismo , Metabolômica/métodos , Aminoácidos/metabolismo , Aminoácidos/sangue , Ração Animal/análise , Proteínas Alimentares/metabolismo , Dieta , MasculinoRESUMO
Background: Mobile health (mHealth) systems are a promising alternative for rehabilitation of hip fracture, addressing constrained healthcare resources. Half of older adults fails to recover their pre-fracture routines, which imposes a burden on caregivers. We aimed to test the effectiveness of the 3-month ActiveHip + mHealth intervention on physical and psychological outcomes of older adults with hip fracture and their family caregivers. Methods: In a multicentre open-label randomised controlled trial conducted across 3 hospitals in Andalusia (Spain), patients older than 65 with a hip fracture, who were previously independent and lacked cognitive impairment were recruited alongside with their caregivers. Participants were randomly allocated (1:1) to the intervention group (ActiveHip+) or control (usual care) group. The intervention group underwent a 12-week health education and tele-rehabilitation programme through the ActiveHip + mHealth intervention. The primary outcome, physical performance, was assessed using the Short Physical Performance Battery at three time points: at hospital discharge (baseline), 3-month after surgery (post intervention) and 1-year after surgery follow-up. Primary analyses of primary outcomes and safety data followed an intention-to-treat approach. This study is registered at ClinicalTrials.gov, NCT04859309. Findings: Between June 1st, 2021 and June 30th, 2022 data from 105 patients and their caregivers were analysed. Patients engaged in the ActiveHip + mHealth intervention (mean 7.11 points, SE 0.33) showed higher physical performance compared with patients allocated in the control group (mean 5.71 points, SE 0.32) at 3 months after surgery (mean difference in change from baseline 1.40 points, SE 0.36; puncorrected = 0.00011). These benefits were not maintained at 1-year after surgery follow-up (mean difference in change from baseline 0.19 points, SE 0.47; puncorrected = 0.68). No adverse events, including falls and refractures, were reported during the tele-rehabilitation sessions. At 3-months, the intervention group had 2 falls, compared to 4 in the control group, with no observed refractures. At the 1-year follow-up, the intervention group experienced 7 falls and 1 refracture, while the control group had 13 falls and 2 refractures. Interpretation: This study suggests that the ActiveHip + mHealth intervention may be effective for recovering physical performance in older adults with hip fracture. Importantly, the implementation of ActiveHip + into daily clinical practice may be feasible and has already been adopted in 18 hospitals, mostly in Spain but also in Belgium and Portugal. Thus, ActiveHip + could offer a promising solution when rehabilitation resources are limited. However, its dependence on caregiver support and the exclusion of participants with cognitive impairment makes it necessary to be cautious about its applicability. In addition, the non-maintenance of the effectiveness at 1-year follow-up highlights the need of refinement the ActiveHip + intervention to promote long-lasting behavioural changes. Funding: EIT Health and the Ramón y Cajal 2021 Excellence Research Grant action from the Spanish Ministry of Science and Innovation.
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Urban evolutionary ecology is inherently interdisciplinary. Moreover, it is a field with global significance. However, bringing researchers and resources together across fields and countries is challenging. Therefore, an online collaborative research hub, where common methods and best practices are shared among scientists from diverse geographic, ethnic, and career backgrounds would make research focused on urban evolutionary ecology more inclusive. Here, we describe a freely available online research hub for toolkits that facilitate global research in urban evolutionary ecology. We provide rationales and descriptions of toolkits for: (1) decolonizing urban evolutionary ecology; (2) identifying and fostering international collaborative partnerships; (3) common methods and freely-available datasets for trait mapping across cities; (4) common methods and freely-available datasets for cross-city evolutionary ecology experiments; and (5) best practices and freely available resources for public outreach and communication of research findings in urban evolutionary ecology. We outline how the toolkits can be accessed, archived, and modified over time in order to sustain long-term global research that will advance our understanding of urban evolutionary ecology.
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INTRODUCTION: Osteoporotic hip fracture is a major health problem. Falls, the primary cause, might lead to a persistent fear of falling (FoF) among older adults, affecting their daily activities and rehabilitation. While in-person interventions exist, limited research is available on the effects of tele-rehabilitation on the FoF after a hip fracture. Thus, this study aims to test the association of the @ctivehip tele-rehabilitation programme on reducing the levels of FoF experienced by both older adults with hip fracture and their family caregivers. METHODS: A non-randomised controlled trial (ClinicalTrials.gov; Identifier: NCT02968589) that compared a webpage-based tele-rehabilitation (@ctivehip) against usual care. Fear of falling was assessed using the Short Falls Efficacy Scale-International. Patients' functional status was evaluated using the Functional Independence Measure. Physical performance was assessed by the Timed Up and Go test and Short Physical Performance Battery. We conducted a per-protocol analysis as the primary outcome, and an intention-to-treat approach as secondary analysis. RESULTS: A total of 71 patients with hip fracture (78.75 ± 6.12 years, 75% women) and their family caregivers participated. Participants in the intervention showed a higher decrease in FoF in comparison to those in the usual care (0.5 Cohen's d; p = 0.042). The reduction in FoF resulting from participation in the tele-rehabilitation programme was mediated by improvements in functional status by 79%. The @ctivehip programme did not decrease FoF of family caregivers. DISCUSSION: @ctivehip is associated with a reduction of the FoF in older adults with hip fractures, but not in their family caregivers, with the reduction being mostly explained by improvements in the patients' functional status. Although the intervention seems promising, it should not be applied in clinical settings until confirmed by appropriate-designed randomised clinical trials.
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During early development, gene expression is tightly regulated. However, how genome organization controls gene expression during the transition from naïve embryonic stem cells to epiblast stem cells is still poorly understood. Using single-molecule microscopy approaches to reach nanoscale resolution, we show that genome remodeling affects gene transcription during pluripotency transition. Specifically, after exit from the naïve pluripotency state, chromatin becomes less compacted, and the OCT4 transcription factor has lower mobility and is more bound to its cognate sites. In epiblast cells, the active transcription hallmark, H3K9ac, decreases within the Oct4 locus, correlating with reduced accessibility of OCT4 and, in turn, with reduced expression of Oct4 nascent RNAs. Despite the high variability in the distances between active pluripotency genes, distances between Nodal and Oct4 decrease during epiblast specification. In particular, highly expressed Oct4 alleles are closer to nuclear speckles during all stages of the pluripotency transition, while only a distinct group of highly expressed Nodal alleles are in close proximity to Oct4 when associated with a nuclear speckle in epiblast cells. Overall, our results provide new insights into the role of the spatiotemporal genome remodeling during mouse pluripotency transition and its correlation with the expression of key pluripotency genes.
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Genoma , Camadas Germinativas , Células-Tronco Embrionárias Murinas , Fator 3 de Transcrição de Octâmero , Animais , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Células-Tronco Embrionárias Murinas/citologia , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Camadas Germinativas/citologia , Camadas Germinativas/metabolismo , Genoma/genética , Regulação da Expressão Gênica no Desenvolvimento , Cromatina/metabolismo , Cromatina/genética , Diferenciação Celular/genética , Imagem Individual de Molécula/métodos , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/citologia , Histonas/metabolismo , Histonas/genética , Montagem e Desmontagem da CromatinaRESUMO
When new antitumor therapy drugs are discovered, it is essential to address new target molecules from the point of view of chemical structure and to carry out efficient and systematic evaluation. In the case of natural products and derived compounds, it is of special importance to investigate chemomodulation to further explore antitumoral pharmacological activities. In this work, the compound podophyllic aldehyde, a cyclolignan derived from the chemomodulation of the natural product podophyllotoxin, has been evaluated for its viability, influence on the cell cycle, and effects on intracellular signaling. We used functional proteomics characterization for the evaluation. Compared with the FDA-approved drug etoposide (another podophyllotoxin derivative), we found interesting results regarding the cytotoxicity of podophyllic aldehyde. In addition, we were able to observe the effect of mitotic arrest in the treated cells. The use of podophyllic aldehyde resulted in increased cytotoxicity in solid tumor cell lines, compared to etoposide, and blocked the cycle more successfully than etoposide. High-throughput analysis of the deregulated proteins revealed a selective antimitotic mechanism of action of podophyllic aldehyde in the HT-29 cell line, in contrast with other solid and hematological tumor lines. Also, the apoptotic profile of podophyllic aldehyde was deciphered. The cell death mechanism is activated independently of the cell cycle profile. The results of these targeted analyses have also shown a significant response to the signaling of kinases, key proteins involved in signaling cascades for cell proliferation or metastasis. Thanks to this comprehensive analysis of podophyllic aldehyde, remarkable cytotoxic, antimitotic, and other antitumoral features have been discovered that will repurpose this compound for further chemical transformations and antitumoral analysis.
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Ciclo Celular , Podofilotoxina , Proteômica , Humanos , Podofilotoxina/farmacologia , Podofilotoxina/análogos & derivados , Podofilotoxina/química , Proteômica/métodos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Etoposídeo/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Células HT29 , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
Enzymatic degradation of algae cell wall carbohydrates by microorganisms is under increasing investigation as marine organic matter gains more value as a sustainable resource. The fate of carbon in the marine ecosystem is in part driven by these degradation processes. In this study, we observe the microbiome dynamics of the macroalga Fucus vesiculosus in 25-day-enrichment cultures resulting in partial degradation of the brown algae. Microbial community analyses revealed the phylum Pseudomonadota as the main bacterial fraction dominated by the genera Marinomonas and Vibrio. More importantly, a metagenome-based Hidden Markov model for specific glycosyl hydrolyses and sulphatases identified Bacteroidota as the phylum with the highest potential for cell wall degradation, contrary to their low abundance. For experimental verification, we cloned, expressed, and biochemically characterised two α-L-fucosidases, FUJM18 and FUJM20. While protein structure predictions suggest the highest similarity to a Bacillota origin, protein-protein blasts solely showed weak similarities to defined Bacteroidota proteins. Both enzymes were remarkably active at elevated temperatures and are the basis for a potential synthetic enzyme cocktail for large-scale algal destruction.
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Parede Celular , Fucus , Metagenômica , Parede Celular/metabolismo , Fucus/metabolismo , Fucus/genética , Fucus/microbiologia , Metagenômica/métodos , Bacteroidetes/genética , Bacteroidetes/enzimologia , Metagenoma , Microbiota , FilogeniaRESUMO
Red rice has been proposed as a super-food. Accordingly, the nutritional properties (AOAC), as well as its chemical composition, including sugars (HPLC-RI), organic acids (UFLC-PDA), tocopherols (HPLD-FD), and phenolic compounds (LC-DAD-ESI/MSn), together with the main bioactive properties (antioxidant, cytotoxic, antiproliferative, and antibacterial activities), were evaluated to access its nutritional benefits and health improvement potential. The most abundant macronutrients found were carbohydrates (87.2 g/100 g dw), proceeded by proteins (9.1 g/100 g dw), fat (2.6 g/100 g dw), and ash (1.1 g/100 g dw). Sucrose and raffinose were the only detected sugars, with sucrose presenting the maximum concentration (0.74 g/100 g dw). MUFAs and PUFAs were the predominant fatty acids (40.7% and 31%, respectively). Among the two detected tocopherol isoforms, γ-tocopherol (0.67 mg/100 g dw) predominated over α-tocopherol. The phenolic compounds profile, majorly composed of flavan-3-ols, should be associated with the detected bioactivities, which may provide biological benefits to human health beyond the primary nutritional effect. Overall, the bioactive potential of red rice was comprehensively accessed.