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1.
Proc Natl Acad Sci U S A ; 120(52): e2312480120, 2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38134197

RESUMEN

Tetrafluoromethane (CF4), the simplest perfluorocarbons, is a permanently potent greenhouse gas due to its powerful infrared radiation adsorption capacity. The highly symmetric and robust C-F bond structure makes its activation a great challenge. Herein, we presented an innovated approach that efficiently activates C-F bond utilizing protonated sulfate (-HSO4) modified Al2O3@ZrO2 (S-Al2O3@ZrO2) catalyst, resulting in highly efficient CF4 decomposition. By combining in situ infrared spectroscopy tests and density function theory simulations, we demonstrate that the introduced -HSO4 proton donor has a stronger interaction on the C-F bond than the hydroxyl (-OH) proton donor, which can effectively stretch the C-F bond for its activation. Consequently, the obtained S-Al2O3@ZrO2 catalyst achieved a stable 100% CF4 decomposition at a record low temperature of 580 °C with a turnover frequency value of ~8.3 times higher than the Al2O3@ZrO2 catalyst without -HSO4 modification, outperforming the previously reported results. This work paves a new way for achieving efficient C-F bond activation to decompose CF4 at a low temperature.

2.
Mol Syst Biol ; 20(8): 933-951, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38918600

RESUMEN

The variability of proteins at the sequence level creates an enormous potential for proteome complexity. Exploring the depths and limits of this complexity is an ongoing goal in biology. Here, we systematically survey human and plant high-throughput bottom-up native proteomics data for protein truncation variants, where substantial regions of the full-length protein are missing from an observed protein product. In humans, Arabidopsis, and the green alga Chlamydomonas, approximately one percent of observed proteins show a short form, which we can assign by comparison to RNA isoforms as either likely deriving from transcript-directed processes or limited proteolysis. While some detected protein fragments align with known splice forms and protein cleavage events, multiple examples are previously undescribed, such as our observation of fibrocystin proteolysis and nuclear translocation in a green alga. We find that truncations occur almost entirely between structured protein domains, even when short forms are derived from transcript variants. Intriguingly, multiple endogenous protein truncations of phase-separating translational proteins resemble cleaved proteoforms produced by enteroviruses during infection. Some truncated proteins are also observed in both humans and plants, suggesting that they date to the last eukaryotic common ancestor. Finally, we describe novel proteoform-specific protein complexes, where the loss of a domain may accompany complex formation.


Asunto(s)
Arabidopsis , Proteómica , Arabidopsis/genética , Arabidopsis/metabolismo , Humanos , Proteómica/métodos , Chlamydomonas/metabolismo , Chlamydomonas/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteoma/genética , Proteolisis , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Empalme Alternativo
3.
Am J Respir Crit Care Med ; 209(11): 1338-1350, 2024 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-38259174

RESUMEN

Rationale: Pharmacological improvement of cystic fibrosis transmembrane conductance regulator (CFTR) function with elexacaftor/tezacaftor/ivacaftor (ETI) provides unprecedented improvements in lung function and other clinical outcomes in patients with cystic fibrosis (CF). However, ETI effects on impaired mucosal homeostasis and host defense at the molecular and cellular levels in the airways of patients with CF remain unknown. Objectives: To investigate effects of ETI on the transcriptome of nasal epithelial and immune cells from children with CF at the single-cell level. Methods: Nasal swabs from 13 children with CF and at least one F508del allele aged 6 to 11 years were collected at baseline and 3 months after initiation of ETI, subjected to single-cell RNA sequencing, and compared with swabs from 12 age-matched healthy children. Measurements and Main Results: Proportions of CFTR-positive cells were decreased in epithelial basal, club, and goblet cells, but not in ionocytes, from children with CF at baseline and were restored by ETI therapy to nearly healthy levels. Single-cell transcriptomics revealed an impaired IFN signaling and reduced expression of major histocompatibility complex classes I and II encoding genes in epithelial cells of children with CF at baseline, which was partially restored by ETI. In addition, ETI therapy markedly reduced the inflammatory phenotype of immune cells, particularly of neutrophils and macrophages. Conclusions: Pharmacological improvement of CFTR function improves innate mucosal immunity and reduces immune cell inflammatory responses in the upper airways of children with CF at the single-cell level, highlighting the potential to restore epithelial homeostasis and host defense in CF airways by early initiation of ETI therapy.


Asunto(s)
Aminofenoles , Benzodioxoles , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Homeostasis , Humanos , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/inmunología , Fibrosis Quística/fisiopatología , Niño , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Femenino , Masculino , Benzodioxoles/uso terapéutico , Benzodioxoles/farmacología , Aminofenoles/uso terapéutico , Aminofenoles/farmacología , Quinolonas/uso terapéutico , Quinolonas/farmacología , Indoles/uso terapéutico , Indoles/farmacología , Combinación de Medicamentos , Quinolinas/uso terapéutico , Quinolinas/farmacología , Pirazoles/uso terapéutico , Pirazoles/farmacología , Pirroles/uso terapéutico , Pirroles/farmacología , Mucosa Nasal/inmunología , Piridinas/uso terapéutico , Piridinas/farmacología
4.
J Proteome Res ; 23(4): 1221-1231, 2024 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-38507900

RESUMEN

Proteins usually execute their biological functions through interactions with other proteins and by forming macromolecular complexes, but global profiling of protein complexes directly from human tissue samples has been limited. In this study, we utilized cofractionation mass spectrometry (CF-MS) to map protein complexes within the postmortem human brain with experimental replicates. First, we used concatenated anion and cation Ion Exchange Chromatography (IEX) to separate native protein complexes in 192 fractions and then proceeded with Data-Independent Acquisition (DIA) mass spectrometry to analyze the proteins in each fraction, quantifying a total of 4,804 proteins with 3,260 overlapping in both replicates. We improved the DIA's quantitative accuracy by implementing a constant amount of bovine serum albumin (BSA) in each fraction as an internal standard. Next, advanced computational pipelines, which integrate both a database-based complex analysis and an unbiased protein-protein interaction (PPI) search, were applied to identify protein complexes and construct protein-protein interaction networks in the human brain. Our study led to the identification of 486 protein complexes and 10054 binary protein-protein interactions, which represents the first global profiling of human brain PPIs using CF-MS. Overall, this study offers a resource and tool for a wide range of human brain research, including the identification of disease-specific protein complexes in the future.


Asunto(s)
Proteínas , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Proteínas/química , Cromatografía Líquida de Alta Presión/métodos , Cromatografía por Intercambio Iónico/métodos , Encéfalo , Proteoma/análisis
5.
Mol Med ; 30(1): 115, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39112965

RESUMEN

BACKGROUND: Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use a sheep model of CF (CFTR-/-) to examine the evolution of pancreatic disease through gestation. METHODS: Fetal pancreas was collected at six time points from 50-days of gestation through to term, which is equivalent to ~ 13 weeks to term in human. RNA was extracted from tissue for bulk RNA-seq and single cells were prepared from 80-day, 120-day and term samples for scRNA-seq. Data were validated by immunochemistry. RESULTS: Transcriptomic evidence from bulk RNA-seq showed alterations in the CFTR-/- pancreas by 65-days of gestation, which are accompanied by marked pathological changes by 80-days of gestation. These include a fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar loss. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CFTR-/- animals at 80- and 120-days gestation, as are stellate cells at term. CONCLUSION: The transcriptomic changes and cellular imbalance that we observe likely have pivotal roles in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent pancreatic destruction in CF.


Asunto(s)
Biomarcadores , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Modelos Animales de Enfermedad , Células Estrelladas Pancreáticas , Fibrosis Quística/genética , Fibrosis Quística/metabolismo , Fibrosis Quística/patología , Animales , Células Estrelladas Pancreáticas/metabolismo , Células Estrelladas Pancreáticas/patología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Femenino , Ovinos , Páncreas/metabolismo , Páncreas/patología , Embarazo , Enfermedades Pancreáticas/genética , Enfermedades Pancreáticas/metabolismo , Enfermedades Pancreáticas/patología , Transcriptoma , Humanos , Perfilación de la Expresión Génica
6.
BMC Plant Biol ; 24(1): 118, 2024 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-38368386

RESUMEN

BACKGROUND: Spot blotch is a serious foliar disease of barley (Hordeum vulgare L.) plants caused by Bipolaris sorokiniana, which is a hemibiotrophic ascomycete that has a global impact on productivity. Some Trichoderma spp. is a promising candidate as a biocontrol agent as well as a plant growth stimulant. Also, the application of nanomaterials in agriculture limits the use of harmful agrochemicals and helps improve the yield of different crops. The current study was carried out to evaluate the effectiveness of Trichoderma. cf. asperellum and the biosynthesized titanium dioxide nanoparticles (TiO2 NPs) to manage the spot blotch disease of barley caused by B. sorokiniana and to assess the plant's innate defense response. RESULTS: Aloe vera L. aqueous leaf extract was used to biosynthesize TiO2 NPs by reducing TiCl4 salt into TiO2 NPs and the biosynthesized NPs were detected using SEM and TEM. It was confirmed that the NPs are anatase-crystalline phases and exist in sizes ranging from 10 to 25 nm. The T. cf. asperellum fungus was detected using morphological traits and rDNA ITS analysis. This fungus showed strong antagonistic activity against B. sorokiniana (57.07%). Additionally, T. cf. asperellum cultures that were 5 days old demonstrated the best antagonistic activity against the pathogen in cell-free culture filtrate. Also, B. sorokiniana was unable to grow on PDA supplemented with 25 and 50 mg/L of TiO2 NPs, and the diameter of the inhibitory zone increased with increasing TiO2 NPs concentration. In an in vivo assay, barley plants treated with T. cf. asperellum or TiO2 NPs were used to evaluate their biocontrol efficiency against B. sorokiniana, in which T. cf. asperellum and TiO2 NPs enhanced the growth of the plant without displaying disease symptoms. Furthermore, the physiological and biochemical parameters of barley plants treated with T. cf. asperellum or TiO2 NPs in response to B. sorokiniana treatment were quantitively estimated. Hence, T. cf. asperellum and TiO2 NPs improve the plant's tolerance and reduce the growth inhibitory effect of B. sorokiniana. CONCLUSION: Subsequently, T. cf. asperellum and TiO2 NPs were able to protect barley plants against B. sorokiniana via enhancement of chlorophyll content, improvement of plant health, and induction of the barley innate defense system. The present work emphasizes the major contribution of T. cf. asperellum and the biosynthesized TiO2 NPs to the management of spot blotch disease in barley plants, and ultimately to the enhancement of barley plant quality and productivity.


Asunto(s)
Bipolaris , Hordeum , Hypocreales , Nanopartículas , Titanio , Trichoderma , Hordeum/genética , Enfermedades de las Plantas/microbiología
7.
Small ; 20(30): e2312187, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38501874

RESUMEN

Zn dendrite growth and side reactions restrict the practical use of Zn anode. Herein, the design of a novel 3D hierarchical structure is demonstrated with self-zincophilic dual-protection constructed by ZnO and Zn nanoparticles immobilized on carbon fibers (ZnO/Zn⊂CF) as a versatile host on the Zn surface. The unique 3D frameworks with abundant zinc nucleation storage sites can alleviate the structural stress during the plating/stripping process and overpower Zn dendrite growth by moderating Zn2+ flux. Moreover, given the dual protection design, it can reduce the contact area between active zinc and electrolyte, inhibiting hydrogen evolution reactions. Importantly, density functional theory calculations and experimental results confirm that the introduced O atoms in ZnO/Zn⊂CF enhance the interaction between Zn2+ and the host and reduce Zn nucleation overpotential. As expected, the ZnO/Zn⊂CF-Zn electrode exhibits stable Zn plating/stripping with low polarization for 4200 h at 0.2 mA cm-2 and 0.2 mAh cm-2. Furthermore, the symmetrical cell displays a significantly long cycling life of over 1800 h, even at 30 mA cm-2. The fabricated full cells also show impressive cycling performance when coupled with V2O3 cathodes.

8.
New Phytol ; 243(4): 1522-1538, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38922927

RESUMEN

Leaf mould, caused by Fulvia fulva, is a devastating disease of tomato plants. In many commercial tomato cultivars, resistance to this disease is governed by the Cf-9 locus, which encodes five paralogous receptor-like proteins. Two of these proteins confer resistance: Cf-9C recognises the previously identified F. fulva effector Avr9 and provides resistance during all plant growth stages, while Cf-9B recognises the yet-unidentified F. fulva effector Avr9B and provides mature plant resistance only. In recent years, F. fulva strains have emerged that can overcome the Cf-9 locus, with Cf-9C circumvented through Avr9 deletion. To understand how Cf-9B is circumvented, we set out to identify Avr9B. Comparative genomics, transient expression assays and gene complementation experiments were used to identify Avr9B, while gene sequencing was used to assess Avr9B allelic variation across a world-wide strain collection. A strict correlation between Avr9 deletion and resistance-breaking mutations in Avr9B was observed in strains recently collected from Cf-9 cultivars, whereas Avr9 deletion but no mutations in Avr9B were observed in older strains. This research showcases how F. fulva has evolved to sequentially break down the Cf-9 locus and stresses the urgent need for commercial tomato cultivars that carry novel, stacked resistance genes active against this pathogen.


Asunto(s)
Resistencia a la Enfermedad , Enfermedades de las Plantas , Hojas de la Planta , Solanum lycopersicum , Solanum lycopersicum/microbiología , Solanum lycopersicum/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/inmunología , Resistencia a la Enfermedad/genética , Hojas de la Planta/microbiología , Hojas de la Planta/genética , Sitios Genéticos , Alelos , Basidiomycota/fisiología , Mutación/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
9.
Chemistry ; 30(34): e202401008, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38624085

RESUMEN

Here we report B(C6F5)3/CPA-catalyzed enantioselective aza-Diels-Alder reaction of 3,3-difluoro-2-Aryl-3H-indoles with unactivated dienes to access chiral 10,10-difluoro-tetrahydropyrido[1,2-a]indoles. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 10,10-difluoro-tetrahydropyrido[1,2-a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity.

10.
Med Mycol ; 62(3)2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38444173

RESUMEN

Limited data on the clinical management of drug-drug interactions between triazoles and Cystic Fibrosis transmembrane conductance regulator (CFTR) modulators are available. We retrospectively evaluated azole target attainment and dose adaptations in patients from two Dutch CF centres concomitantly receiving triazoles and CFTR modulators. In total, 21 patients with 59 triazole trough concentrations were evaluated. Subtherapeutic concentrations were frequently observed, especially for itraconazole and voriconazole. Of the investigated antifungal agents, posaconazole appears the most preferable option. Our results emphasize the importance of adequate management of this interaction and underpin the added value of therapeutic drug monitoring of triazoles in this population.


Fungal infections are serious complications in Cystic Fibrosis (CF) patients. We evaluated patients concomitantly receiving triazoles and CF transmembrane conductance regulator modulators: subtherapeutic triazole exposure was frequently observed. Posaconazole appears the preferable antifungal agent.


Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Humanos , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/veterinaria , Estudios Retrospectivos , Triazoles/farmacología , Triazoles/uso terapéutico , Mutación
11.
Artículo en Inglés | MEDLINE | ID: mdl-38937992

RESUMEN

There are two main complementary feeding (CF) approaches: traditional spoon-feeding (TSF) and baby-led weaning (BLW). Many parents and healthcare professionals have concerns about the risk of choking associated with BLW. Since asphyxia is one of infants' main causes of death, this study aims to understand the influence of the CF approach adopted by caregivers on infants' risk of choking. A systematic review was performed. The search was conducted through PubMed, Scopus, and Web of Science databases. We included randomized controlled trials or observational studies published between January 2010 and November 2023, with a clear definition of the intervention and directly assessing the risk of choking. After the selection procedure, 7 of the 165 studies initially identified were included. No study reported statistically significant differences in the risk of choking between babies following BLW, baby-led introduction to solids (BLISS), and TSF. In five studies, although not statistically significant, infants in the TSF group had more choking episodes than those in the BLW or BLISS groups. The risk of choking does not seem to be associated with the CF approach. Instead, it may be related to the familiarity of the baby with each texture and the parent's understanding of the information about how to minimize the risk of choking. Recall bias may be present in all included studies. Advice on how to modify foods to make them safer needs to be clearer and reinforced to all parents.

12.
BMC Pulm Med ; 24(1): 348, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026320

RESUMEN

BACKGROUND: Outcomes for individuals with cystic fibrosis (CF) have improved due to highly effective modulator therapy (HEMT). However, lung transplant (LTx) remains an important treatment for people with advanced lung disease. This study assessed attitudes and knowledge about LTx in the HEMT era. METHODS: All patients from the University of Washington CF clinic were surveyed March 25-May 30, 2020. Questions addressed self-rated LTx preparedness and knowledge, as well as barriers and facilitators to discussing LTx. Demographic and clinical data were extracted from the electronic health record. RESULTS: There were 159/224 (71%) responses. Respondents had a median forced expiratory volume in one second (FEV1) of 70%, and 142 (89%) were on modulatory therapy. One hundred thirteen (71%) respondents felt that it was moderately or very important to be prepared to make decisions about LTx, though only 56 (35%) felt moderately or very prepared. Only 83 (30%) and 47 (52%) participants correctly answered questions about life expectancy and improved quality of life after LTx, respectively. Respondents with Medicaid insurance less frequently answered questions correctly. The most common barriers to discussing LTx were fear of being a burden on loved ones for 58 respondents (36%) and cost of LTx for 46 (29%). Most participants (94%) trusted their CF doctor, and 75% of participants selected trust as a facilitator for LTx discussions. CONCLUSIONS: Many individuals with CF, especially those with lower socioeconomic status, lacked knowledge and did not feel very prepared for decisions about LTx. Earlier education and discussions about LTx represent an area for improvement in CF care.


Asunto(s)
Fibrosis Quística , Conocimientos, Actitudes y Práctica en Salud , Trasplante de Pulmón , Humanos , Fibrosis Quística/cirugía , Fibrosis Quística/psicología , Masculino , Femenino , Adulto , Encuestas y Cuestionarios , Calidad de Vida , Persona de Mediana Edad , Adulto Joven
13.
Sensors (Basel) ; 24(13)2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-39000843

RESUMEN

In this paper, we investigate a cell-free massive multiple-input multiple-output (CF-mMIMO) system with a reconfigurable intelligent surface (RIS) carried by an unmanned aerial vehicle (UAV), called the UAV-RIS. Compared with the RIS located on the ground, the UAV-RIS has a wider coverage that can reflect all signals from access points (APs) and user equipment (UE). By correlating the UAV location with the Rician K-factor, we derive a closed-form approximation of the UE achievable downlink rate. Based on this, we obtain the optimal UAV location and RIS phase shift that can maximize the UE sum rate through an alternating optimization method. Simulation results have verified the accuracy of the derived approximation and shown that the UE sum rate can be significantly improved with the obtained optimal UAV location and RIS phase shift. Moreover, we find that with a uniform UE distribution, the UAV-RIS should fly to the center of the system, while with an uneven UE distribution, the UAV-RIS should fly above the area where UEs are gathered. In addition, we also design the best trajectory for the UAV-RIS to fly from its initial location to the optimal destination while maintaining the maximum UE sum rate per time slot during the flight.

14.
Int J Mol Sci ; 25(15)2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39126012

RESUMEN

Exposure to ionizing radiation can result in the development of a number of diseases, including cancer, cataracts and neurodegenerative pathologies. Certain occupational groups are exposed to both natural and artificial sources of radiation as a consequence of their professional activities. The development of non-invasive biomarkers to assess the risk of exposure to ionizing radiation for these groups is of great importance. In this context, our objective was to identify epigenetic and molecular biomarkers that could be used to monitor exposure to ionizing radiation. The impact of X-ray exposure on the miRNAs profile and the level of cf mtDNA were evaluated using the RT-PCR method. The levels of pro-inflammatory cytokines in their blood were quantified using the ELISA method. A significant decrease in miR-19a-3p, miR-125b-5p and significant increase in miR-29a-3p was observed in the blood plasma of individuals exposed to X-ray. High levels of pro-inflammatory cytokines and cf mtDNA were also detected. In silico identification of potential targets of these miRNAs was conducted using MIENTURNET. VDAC1 and ALOX5 were identified as possible targets. Our study identified promising biomarkers such as miRNAs and cf mtDNA that showed a dose-dependent effect of X-ray exposure.


Asunto(s)
Biomarcadores , ADN Mitocondrial , Epigénesis Genética , MicroARNs , Humanos , MicroARNs/sangre , MicroARNs/genética , ADN Mitocondrial/sangre , ADN Mitocondrial/genética , Epigénesis Genética/efectos de la radiación , Biomarcadores/sangre , Rayos X/efectos adversos , Masculino , Exposición Profesional/efectos adversos , Adulto , Persona de Mediana Edad , Citocinas/sangre , Citocinas/genética , Femenino
15.
Int J Mol Sci ; 25(7)2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38612387

RESUMEN

Apobec-1 complementation factor (A1CF) functions as an RNA-binding cofactor for APO-BEC1-mediated C-to-U conversion during RNA editing and as a hepatocyte-specific regulator in the alternative pre-mRNA splicing of metabolic enzymes. Its role in RNA editing has not been clearly established. Western blot, co-immunoprecipitation (Co-IP), immunofluorescence (IF), methyl thiazolyl tetrazolium (MTT), and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to examine the role of A1CF beyond RNA editing in renal carcinoma cells. We demonstrated that A1CF interacts with NKRF, independent of RNA and DNA, without affecting its expression or nuclear translocation; however, it modulates p65(Ser536) phosphorylation and IFN-ß levels. Truncation of A1CF or deletion on NKRF revealed that the RRM1 domain of A1CF and the p65 binding motif of NKRF are required for their interaction. Deletion of RRM1 on A1CF abrogates NKRF binding, and the decrease in IFN-ß expression and p65(Ser536) phosphorylation was induced by A1CF. Moreover, full-length A1CF, but not an RRM1 deletion mutant, promoted cell proliferation in renal carcinoma cells. Perturbation of A1CF levels in renal carcinoma cells altered anchorage-independent growth and tumor progression in nude mice. Moreover, p65(Ser536) phosphorylation and IFN-ß expression were lower, but ki67 was higher in A1CF-overexpressing tumor tissues of a xenograft mouse model. Notably, primary and metastatic samples from renal cancer patients exhibited high A1CF expression, low p65(Ser536) phosphorylation, and decreased IFN-ß levels in renal carcinoma tissues compared with the corresponding paracancerous tissues. Our results indicate that A1CF-decreased p65(Ser536) phosphorylation and IFN-ß levels may be caused by A1CF competitive binding to the p65-combined site on NKRF and demonstrate the direct binding of A1CF independent of RNA or DNA in signal pathway regulation and tumor promotion in renal carcinoma cells.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Animales , Humanos , Ratones , Desaminasas APOBEC-1 , Carcinoma de Células Renales/genética , Modelos Animales de Enfermedad , ADN , Neoplasias Renales/genética , Ratones Desnudos , Fosforilación , ARN , Proteínas de Unión al ARN , Interferón beta
16.
Int J Mol Sci ; 25(8)2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38673878

RESUMEN

Irritable bowel syndrome (IBS) involves low-grade mucosal inflammation. Among the various approaches capable of managing the symptoms, physical activity is still under investigation. Despite its benefits, it promotes oxidative stress and inflammation. Mitochondria impacts gut disorders by releasing damage-associated molecular patterns, such as cell-free mtDNA (cf-mtDNA), which support inflammation. This study evaluated the effects of a 12-week walking program on the cf-mtDNA and DNase in 26 IBS and 17 non-IBS subjects. Pro- and anti-inflammatory cytokines were evaluated by ELISA. Digital droplet PCR was used to quantify cf-mtDNA; DNase activity was assessed using a single radial enzyme diffusion assay. PCR-RFLP was used to genotype DNASE1 rs1053874 SNP. Significantly lower IL-10 levels were found in IBS than in non-IBS individuals. Exercise reduced cf-mtDNA in non-IBS subjects but not in IBS patients. DNase activity did not correlate with the cf-mtDNA levels in IBS patients post-exercise, indicating imbalanced cf-mtDNA clearance. Different rs1053874 SNP frequencies were not found between groups. The study confirms the positive effects of regular moderate-intensity physical activity in healthy subjects and its role in cf-mtDNA release and clearance. Walking alone might not sufficiently reduce subclinical inflammation in IBS, based on imbalanced pro- and anti-inflammatory molecules. Prolonged programs are necessary to investigate their effects on inflammatory markers in IBS.


Asunto(s)
Ácidos Nucleicos Libres de Células , ADN Mitocondrial , Síndrome del Colon Irritable , Caminata , Humanos , Síndrome del Colon Irritable/genética , Síndrome del Colon Irritable/metabolismo , ADN Mitocondrial/genética , Masculino , Femenino , Adulto , Ácidos Nucleicos Libres de Células/genética , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Desoxirribonucleasas/metabolismo , Desoxirribonucleasas/genética , Ejercicio Físico/fisiología
17.
J Fish Biol ; 104(5): 1645-1650, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38402691

RESUMEN

Areas of importance to Southern Ocean skates are poorly defined. Here, we identify a deepwater skate egg case nursery in a discrete location at ~460 m depth off Cape Adare in the Southern Ocean. This is the first confirmed observation of a skate nursery area in the Ross Sea and only the second observation for the Southern Ocean. The morphology and size of the egg cases were consistent with the genus Bathyraja and most likely belong to the Bathyraja sp. (cf. eatonii). The nursery occurs within the "no take" General Protection Zone of the Ross Sea region marine protected area, where commercial fishing is prohibited.


Asunto(s)
Océanos y Mares , Óvulo , Rajidae , Animales , Femenino
18.
Molecules ; 29(14)2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39064882

RESUMEN

Heterostructure catalysts are highly anticipated in the field of photocatalytic water splitting. AlN/Sc2CF2 and GaN/Sc2CF2 heterostructures are proposed in this work, and the electronic structures were revealed with the first-principles method to explore their photocatalytic properties for water splitting. The results found that the thermodynamically stable AlN/Sc2CF2 and GaN/Sc2CF2 heterostructures are indirect semiconductors with reduced band gaps of 1.75 eV and 1.84 eV, respectively. These two heterostructures have been confirmed to have type-Ⅰ band alignments, with both VBM and CBM contributed to by the Sc2CF2 layer. AlN/Sc2CF2 and GaN/Sc2CF2 heterostructures exhibit the potential for photocatalytic water splitting as their VBM and CBM stride over the redox potential of water. Gibbs free energy changes in HER occurring on AlN/Sc2CF2 and GaN/Sc2CF2 heterostructures are as low as -0.31 eV and -0.59 eV, respectively. The Gibbs free energy change in HER on the AlN (GaN) layer is much lower than that on the Sc2CF2 surface, owing to the stronger adsorption of H on AlN (GaN). The AlN/Sc2CF2 and GaN/Sc2CF2 heterostructures possess significant improvements in absorption range and intensity compared to monolayered AlN, GaN, and Sc2CF2. In addition, the band gaps, edge positions, and absorption properties of AlN/Sc2CF2 and GaN/Sc2CF2 heterostructures can be effectively tuned with strains. All the results indicate that AlN/Sc2CF2 and GaN/Sc2CF2 heterostructures are suitable catalysts for photocatalytic water splitting.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38980550

RESUMEN

Cystic Fibrosis (CF) is a progressive condition resulting in reduced lung function and strongly associated with elevated anxiety and depression symptoms. Self-concept refers to an individual's overarching sense of identity, a positive level of which is widely associated with reduced anxiety and depression. There is a significant lack of self-concept research within CF. This study explores the association between self-concept and anxiety and depression in adults with CF. 64 adults living with CF in Western Australia completed validated online questionnaires (Generalised Anxiety Disorder-7, Patient Health Questionnaire-9, Tennessee Self-Concept Questionnaire 2: Short-Form) and consented to the collection of medical data. Descriptive, t-test, correlation and multiple regression analysis were undertaken. Higher levels of self-concept were associated with lower levels of anxiety and depression symptoms. Lower self-concept levels were a significant predictor of increased anxiety and depression symptoms after accounting for physical health status. Mean self-concept scores for those who required mental health intervention were significantly lower compared to those that did not. This study identifies a significant relationship between self-concept and anxiety and depression in adults with CF. Further research is required to establish causation and test the feasibility of self-concept interventions in reducing anxiety and depression symptoms.

20.
Environ Geochem Health ; 46(8): 279, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958829

RESUMEN

The present study focused on to determine the concentration and health risk of heavy metals (Cu, Pb, Zn, Cd, Hg, Cr) in e-waste contaminated soils collected from different provinces of Pakistan. Further, the impact of heavy metals on soil enzyme activities and microbial community was also investigated. The concentration (mg/kg) of Hg, Zn, Fe, Cu, Pb, Cd, and Cr ranged between 0-0.258, 2.284-6.587, 3.005-40.72, 8.67-36.88, 12.05-35.03, 1.03-2.43, and 33.13-60.05, respectively. The results revealed that Lahore site of Punjab province indicated more concentration of heavy metals as compared to other sites. The level of Cr at all sites whereas Hg at only two sites exceeds the World Health Organization standards (WHO) for soil. Soil enzyme activity exhibited dynamic trend among the sites. Maximum enzyme activity was observed for urease followed by phosphatase and catalase. Contamination factor (Cf), Pollution load index (PLI), and geo-accumulation index (Igeo) results showed that all the sites are highly contaminated with Cu, Cd, and Pb. Hazard index (HI) was less than 1 for children and adults suggesting non-carcinogenic health risk. Principle component analysis results depicted relation among Cr, Fr, catalase, and actinomycetes; Cd, OM, urease, and bacteria, and Pb, Cu, Zn, Hg, and phosphatase, suggesting soil enzymes and microbial community profiles were influenced by e-waste pollution. Therefore, there is a dire need to introduce sustainable e-waste recycling techniques as well as to make stringent e-waste management policies to reduce further environmental contamination.


Asunto(s)
Residuos Electrónicos , Metales Pesados , Microbiología del Suelo , Contaminantes del Suelo , Metales Pesados/análisis , Pakistán , Contaminantes del Suelo/análisis , Medición de Riesgo , Humanos , Monitoreo del Ambiente/métodos , Instalaciones de Eliminación de Residuos , Suelo/química
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