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Reproduction by perennial plants varies from being relatively constant over years to the production of massive and synchronous seed crops at irregular intervals, a reproductive strategy called mast seeding. The sources of interspecific differences in the extent of interannual variation in seed production are largely unknown. We conducted a global meta-analysis of animal-dispersed species to quantify how the interannual variability in seed crops produced by plants can be explained by the seed mass, dispersal mode, phylogeny, and climate. Phylogenetic analysis indicated that the interannual variations in seed production and seed mass tended to be similar in related species due to their shared evolution. The interannual variation in seed production was 1.22 times higher in synzoochorous species dispersed by scatter-hoarders compared with endozoochorous species dispersed by frugivores. Furthermore, the production of small seeds was associated with higher interannual variation in seed production, although synzoochorous species produced larger seeds than endozoochorous species. Precipitation rather than temperature had a significant positive effect on the interannual variation in seed production. The seed mass and dispersal mode contributed more to the interannual variation in seed production than phylogeny, climate, and fruit type. Our findings support a long-standing hypothesis that interspecific variation in the masting intensity is largely shaped by interactions between plants and animals.
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OBJECTIVES: To explore the diagnostic efficacy of serum 14-3-3ß protein combined with fractional exhaled nitric oxide (FeNO) and conventional ventilatory lung function parameters in diagnosing bronchial asthma (referred to as "asthma") in children. METHODS: A prospective study included 136 children initially diagnosed with asthma during an acute episode as the asthma group, and 85 healthy children undergoing routine health checks as the control group. The study compared the differences in serum 14-3-3ß protein concentrations between the two groups, analyzed the correlation of serum 14-3-3ß protein with clinical indices, and evaluated the diagnostic efficacy of combining 14-3-3ß protein, FeNO, and conventional ventilatory lung function parameters for asthma in children. RESULTS: The concentration of serum 14-3-3ß protein was higher in the asthma group than in the control group (P<0.001). Serum 14-3-3ß protein showed a positive correlation with the percentage of neutrophils and total serum immunoglobulin E, and a negative correlation with conventional ventilatory lung function parameters (P<0.05). Cross-validation of combined indices showed that the combination of 14-3-3ß protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume had an area under the curve of 0.948 for predicting asthma, with a sensitivity and specificity of 88.9% and 93.7%, respectively, demonstrating good diagnostic efficacy (P<0.001). The model had the best extrapolation. CONCLUSIONS: The combination of serum 14-3-3ß protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume can significantly improve the diagnostic efficacy for asthma in children. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 723-729.
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Proteínas 14-3-3 , Asma , Óxido Nítrico , Humanos , Asma/diagnóstico , Asma/sangre , Asma/fisiopatología , Masculino , Femenino , Niño , Proteínas 14-3-3/sangre , Óxido Nítrico/análisis , Óxido Nítrico/sangre , Preescolar , Estudios Prospectivos , Pruebas de Función Respiratoria , Prueba de Óxido Nítrico Exhalado Fraccionado , Adolescente , Pruebas RespiratoriasRESUMEN
Introduction: In the era of the Internet, online digital traces have become a new way to study the online attention of scenic spots and tourists' purchase behavior. The public's information search on major search platforms is a series of manifestations of potential tourists' attention and interest in scenic spots, but there are few studies on how attention, interest and information search affect potential tourists to generate real purchase behavior. Method: This paper selects four dimensions of short video platform, travel website, search engine and social media to comprehensively measure the online attention of high-quality scenic spots in Yunnan Province, and then establishes a gray association analytic hierarchy process based on the relevant variables of the AISAS model to empirically analyze the primary and secondary factors affecting tourists' purchase behavior. Results: (1) From the perspective of the online attention of scenic spots on different platforms, the intensity of the public's scenic spots online attention on the four types of media platforms is in the order of travel websites, search engines, short videos and social media (2) From the perspective of spatial distribution characteristics, the online attention of high-quality scenic spots in Yunnan Province is unevenly distributed, that is, there is a big difference between the attention of higher star scenic spots and their star rating and popularity, while the attention of low-star scenic spots is not much different from their star rating and popularity (3) From the perspective of spatial agglomeration characteristics, the comprehensive online attention of high-quality scenic spots in Yunnan Province presents the spatial agglomeration characteristics of "the multi-core linkage of high-density in the east and north, and sub-high-density in the south" (4) The factors influencing the purchase behavior of potential tourists are sharing experience, attracting attention, generating interest and searching information. Discussion: By exploring the formation mechanism of high-quality scenic spots online attention in Yunnan Province and the mechanism of its spatial differentiation, this study not only enriches the logical chain of "tourism information source â potential tourists â demand driven â tourism information search â travel preference â destination selection â purchase decision â travel experience â real tourists â feelings after traveling â focus on feedback â tourism information source," but also broadens the application scenarios and application boundaries of travel preference theory and AISAS behavior model to a certain extent.
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Protein N-glycosylation plays a critical role in a wide range of biological processes, and aberrant N-glycosylation is frequently associated with various pathological states. For global N-glycosylation analysis, N-glycans are typically released from glycoproteins mediated by endoglycosidases, primarily peptide N-glycosidase F (PNGase F). However, conventional N-glycan release by in-solution PNGase F is time-consuming and nonreusable. Although some immobilization methods can save time and reduce the enzyme dosage, including affinity interaction and covalent binding, the immobilized PNGase F by these traditional methods may compromises the immobilized enzyme's stability and biofunction. Therefore, a new approach is urgently needed to firmly and steadily immobilize PNGase F. To meet this demand, we have developed a spontaneous and site-specific way to immobilize PNGase F onto magnetic nanoparticles via Spy chemistry. The magnetic nanoparticles were synthesized and modified with SpyTag as a solid surface. The PNGase F fused with SpyCatcher can then be site-specifically and covalently immobilized onto this solid phase, forming a firm isopeptide bond via self-catalysis between the SpyTag peptide and SpyCatcher. Importantly, the immobilization process mediated by mild spy chemistry does not result in PNGase F inactivation; and allows immobilized PNGase F to rapidly release various types of glycans (high-mannose, sialylated, and hybrid) from glycoproteins. Moreover, the immobilized PNGase F exhibited good deglycosylation activity and facilitated good reusability in consecutive reactions. Deglycosylation of clinical samples was completed by the immobilized PNGase F as fast as several minutes.
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The structure of cellulolytic enzyme lignin (CEL) prepared from three bamboo species (Neosinocalamus affinis, Bambusa lapidea, and Dendrocalamus brandisii) has been characterized by different analytical methods. The chemical composition analysis revealed a higher lignin content, up to 32.6% of B. lapidea as compared to that of N. affinis (20.7%) and D. brandisii (23.8%). The results indicated that bamboo lignin was a p-hydroxyphenyl-guaiacyl-syringyl (H-G-S) lignin associated with p-coumarates and ferulates. Advanced NMR analyses displayed that the isolated CELs were extensively acylated at the γ-carbon of the lignin side chain (with either acetate and/or p-coumarate groups). Moreover, a predominance of S over G lignin moieties was found in CELs of N. affinis and B. lapidea, with the lowest S/G ratio observed in D. brandisii lignin. Catalytic hydrogenolysis of lignin demonstrated that 4-propyl-substituted syringol/guaiacol and propanol guaiacol/syringol derived from ß-O-4' moieties, and methyl coumarate/ferulate derived from hydroxycinnamic units were identified as the six major monomeric products. We anticipate that the insights of this work could shed light on the sufficient understanding of lignin, which could open a new avenue to facilitate the efficient utilization of bamboo.
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Bambusa , Lignina , Lignina/química , Pirogalol , Bambusa/química , CatálisisRESUMEN
To clarify the content characteristics of the main active components and mineral elements of Cynomorium songaricum under different habitat conditions, and further explore the relationship between the quality of C. songaricum and habitats, this study took C. songaricum from 25 different habitats in China as the research object, and measured the contents of 8 main active components and 12 mineral elements separately. Diversity analysis, correlation analysis, principal component analysis and cluster analysis were carried out. The results showed that the genetic diversity of total flavonoids, ursolic acid, ether extract, potassium(K), phosphorus(P) and zinc(Zn) in C. songaricum was high. The coefficient of variation of crude polysaccharide, ether extract, gallic acid, protocatechuic aldehyde, catechin, epicatechin, calcium(Ca), sodium(Na), magnesium(Mg), sulfur(S), iron(Fe), manganese(Mn), selenium(Se) and nickel(Ni) were all over 36%, indicating that the quality of C. songaricum was significantly affected by habitats. There were strong synergistic and weak antagonistic effects among the contents of the 8 active components, and complex antagonistic and synergistic effects among the contents of the 12 mineral elements. Principal component analysis revealed that crude polysaccharide, ursolic acid, catechin, epicatechin and total flavonoids could be used as the characteristic components to evaluate the quality of C. songaricum, and Na, copper(Cu), Mn and Ni were the characteristic elements to evaluate the quality of C. songaricum. In cluster ana-lysis, the second group with the main active components as cluster center had better quality in terms of the content of active substances, and the second group with the mineral elements as cluster center had higher utilization potential in the exploitation of mineral elements. This study could provide a basis for resource evaluation and breeding of excellent varieties of C. songaricum in different habitats, and provide a reference for cultivation and identification of C. songaricum.
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Catequina , Cynomorium , Selenio , Fitomejoramiento , Éteres , Éteres de Etila , Flavonoides , Extractos Vegetales , Ácido UrsólicoRESUMEN
In the workflow of global N-glycosylation analysis, endoglycosidase-mediated removal of glycans from glycoproteins is an essential and rate-limiting step. Peptide-N-glycosidase F (PNGase F) is the most appropriate and efficient endoglycosidase for the removal of N-glycans from glycoproteins prior to analysis. Due to the high demand for PNGase F in both basic and industrial research, convenient and efficient methods are urgently needed to generate PNGase F, preferably in the immobilized form to solid phases. However, there is no integrated approach to implement both efficient expression, and site-specific immobilization of PNGase F. Herein, efficient production of PNGase F with a glutamine tag in Escherichia coli and site-specific covalent immobilization of PNGase F with this special tag via microbial transglutaminase (MTG) is described. PNGase F was fused with a glutamine tag to facilitate the co-expression of proteins in the supernatant. The glutamine tag was covalently and site-specifically transformed to primary amine-containing magnetic particles, mediated by MTG, to immobilize PNGase F. Immobilized PNGase F could deglycosylate substrates with identical enzymatic performance to that of the soluble counterpart, and exhibit good reusability and thermal stability. Moreover, the immobilized PNGase F could also be applied to clinical samples, including serum and saliva.
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Glutamina , Transglutaminasas , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa/química , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa/metabolismo , Manosil-Glicoproteína Endo-beta-N-Acetilglucosaminidasa/química , Manosil-Glicoproteína Endo-beta-N-Acetilglucosaminidasa/metabolismo , Glicoproteínas/química , Glicósido Hidrolasas , Polisacáridos/análisis , Fenómenos MagnéticosRESUMEN
Intrauterine growth restriction (IUGR) and exposure to a high-fat diet (HFD) independently increase the risk of cardiovascular disease (CVD) and hyperlipidemia. In our previous studies, IUGR increased blood pressure and promoted vascular remodeling and stiffness in early life, a finding that persisted and was augmented by a maternal HFD through postnatal day (PND) 60. The impact of these findings with aging and the development of hyperlipidemia and atherosclerosis remain unknown. We hypothesized that the previously noted impact of IUGR on hypertension, vascular remodeling, and hyperlipidemia would persist. Adult female rats were fed either a regular diet (RD) or high fat diet (HFD) prior to conception through lactation. IUGR was induced by uterine artery ligation. Offspring were weaned to either RD or HFD through PND 365. For both control (C) and IUGR (I) and rats, this resulted in the following six groups per sex: offspring from RD dams weaned to an RD (CRR and IRR), or offspring from HFD dams weaned to either an RD (CHR and IHR) or to an HFD (CHH and IHH). IHH male and female rats had increased large artery stiffness, a suggestion of fatty streaks in the aorta, and persistent decreased elastin and increased collagen in the aorta and carotid arteries. Post-weaning HFD intake increased blood lipids regardless of IUGR status. IUGR increased HFD-induced mortality. We speculate that HFD-induced risk of CVD and mortality is potentiated by developmental programming of the ECM.
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Aterosclerosis , Enfermedades Cardiovasculares , Femenino , Masculino , Ratas , Animales , Humanos , Retardo del Crecimiento Fetal/etiología , Dieta Alta en Grasa/efectos adversos , Remodelación Vascular , Arteria Uterina , Aterosclerosis/etiologíaRESUMEN
ABSTRACT: Xiao, F, Yang, Y, Xiao, L, Xia, Z, Wang, L, Yang, K, and Wang, S. Reduction of T cells and hsa-miR150-5p in female canoeing athletes: Preliminary evidence between exercise training and immune. J Strength Cond Res 36(11): e106-e113, 2022-This article aims to reveal the alteration of immune profile in teenage canoeing athletes, by which applies a clue for regulation of exercise on human immune. Thirty-one teenagers of female canoeing athletes and age-matched subjects participated in this research. Peripheral leukocytes' microRNAs (miRNAs) were analyzed using Agilent human microRNA 2.0 and gene software. The miRNA candidates were quantified by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). The percentages of various lymphocytes were tested using flow cytometry. There were 6 miRNAs (hsa-miR150-5p, 31-5p, 3659, 4419a, 650, and 8485) lower in canoeing athletes, and the reduction of miR-150 was identified by RT-qPCR ( p = 0.021). Canoeing athletes had lower percent of CD3 + T cells than the subjects with no exercise training had ( p < 0.001), but the ratio of CD4 + to CD8 + and the percent of CD4 + T cells and CD8 + T cells showed no significant difference between these 2 groups. T cells and hsa-miR150-5p are sensitive to the long-time heavy exercise training, and the exercise for winning competition regulates the immune system by inhibiting T cells and hsa-miR150-5p.
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MicroARNs , Deportes Acuáticos , Adolescente , Humanos , Femenino , Reacción en Cadena en Tiempo Real de la Polimerasa , Linfocitos T CD4-Positivos , AtletasRESUMEN
Several studies have indicated a positive effect of exercise (especially resistance exercise) on the mTOR signaling that control muscle protein synthesis and muscle remodeling. However, the relationship between exercise, mTOR activation and leucine-sensing requires further clarification. Two month old Sprague-Dawley rats were subjected to aerobic exercise (treadmill running at 20 m/min, 6° incline for 60 min) and resistance exercise (incremental ladder climbing) for 4 weeks. The gastrocnemius muscles were removed for determination of muscle fibers diameter, cross-sectional area (CSA), protein concentration and proteins involved in muscle leucine-sensing and protein synthesis. The results show that 4 weeks of resistance exercise increased the diameter and CSA of gastrocnemius muscle fibers, protein concentration, the phosphorylation of mTOR (Ser2448), 4E-BP1(Thr37/46), p70S6K (Thr389), and the expression of LeuRS, while aerobic exercise just led to a significant increase in protein concentration and the phosphorylation of 4E-BP1(Thr37/46). Moreover, no difference was found for Sestrin2 expression between groups. The current study shows resistance exercise, but not aerobic exercise, may increase muscle protein synthesis and protein deposition, and induces muscle hypertrophy through LeuRS/mTOR signaling pathway. However, further studies are still warranted to clarify the exact effects of vary intensities and durations of aerobic exercise training.
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The present study aimed to investigate the molecular mechanism of the Astragalus-Scorpion drug pair in the treatment of prostate cancer (PCa). We employed network pharmacology and molecular docking technology to retrieving the active ingredients and corresponding targets of Astragalus-Scorpion by using TCMSP, BATMAN-TCM, TCMID and Swiss Target Prediction Databases. The targets related to PCa were retrieved through GeneCards. Cytoscape software was used to construct the 'active ingredient-target disease' network, and GO and KEGG enrichment analyses were performed on the common targets. Autodock software was used for molecular docking verification. In total, 26 active ingredients, 340 potential targets related to active ingredients and 122 common targets were screened from Astragalus-Scorpion drug pair. The core targets of the protein-protein interaction (PPI) network were JUN, AKT1, IL6, MAPK1 and RELA, whereas the core active ingredients were quercetin, kaempferol, formononetin, 7-o-methylisomucronulatol and calycosin. Nearly 762 GO entries and 154 pathways were obtained by using the pathway enrichment analysis. Molecular docking results revealed that quercetin and kaempferol bind to AKT1 and formononetin binds to RELA, all of which were found to be stable bounds.
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Medicamentos Herbarios Chinos , Neoplasias de la Próstata , Animales , Humanos , Masculino , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Neoplasias de la Próstata/tratamiento farmacológico , EscorpionesRESUMEN
Skeletal muscle anabolic resistance (i.e., the decrease in muscle protein synthesis (MPS) in response to anabolic stimuli such as amino acids and exercise) has been identified as a major cause of age-related sarcopenia, to which blunted nutrition-sensing contributes. In recent years, it has been suggested that a leucine sensor may function as a rate-limiting factor in skeletal MPS via small-molecule GTPase. Leucine-sensing and response may therefore have important therapeutic potential in the steady regulation of protein metabolism in aging skeletal muscle. This paper systematically summarizes the three critical processes involved in the leucine-sensing and response process: (1) How the coincidence detector mammalian target of rapamycin complex 1 localizes on the surface of lysosome and how its crucial upstream regulators Rheb and RagB/RagD interact to modulate the leucine response; (2) how complexes such as Ragulator, GATOR, FLCN, and TSC control the nucleotide loading state of Rheb and RagB/RagD to modulate their functional activity; and (3) how the identified leucine sensor leucyl-tRNA synthetase (LARS) and stress response protein 2 (Sestrin2) participate in the leucine-sensing process and the activation of RagB/RagD. Finally, we discuss the potential mechanistic role of exercise and its interactions with leucine-sensing and anabolic responses.
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The chemical components and antioxidant activity of 16 Rehmannia glutinosa samples were investigated to reveal the high-quality raw resource for pharmaceutical products. 22 main chemical components were detected with significant content differences (P<0.05). The contents of 14 substances reached the maximum in S1 sample such as catalpol (6.74â mg g-1 ), rehmaionoside A (1.93â mg g-1 ) and rehmannioside D (5.13â mg g-1 ). However, the content distribution of the other eight substances had no obvious change regulation. Three antioxidant evaluation methods commonly showed that S1 sample had strong antioxidant activity with a low IC50 value of 0.022â mg mL-1 , a high ABTS value of 524.196â µmol equiv. Trolox g-1 , and a high FRAP value of 200.517â µmol equiv. Trolox g-1 . Considered the medicinal value, S1 had high quality based on the present phytochemical profiles and antioxidant activity. These results also indicated that the root extracts of R. glutinosa could become useful supplement for pharmaceutical products as new antioxidant agents.
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Antioxidantes/farmacología , Fitoquímicos/farmacología , Rehmannia/química , Aminoácidos/análisis , Cromatografía Liquida/métodos , Raíces de Plantas/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Lignin depolymerization into aromatic monomers with high yields and selectivity is essential for the economic feasibility of biorefinery. However, the relationship between lignin structure and its reactivity for upgradeability is still poorly understood, in large part owing to the difficulty in quantitative characterization of lignin structural properties. To overcome these shortcomings, advanced NMR technologies [2D HSQC (heteronuclear single quantum coherence) and 31 P] were used to accurately quantify lignin functionalities. Diverse lignin samples prepared from Eucalyptus grandis with varying ß-O-4 linkages were subjected to Pd/C-catalyzed hydrogenolysis for efficient C-O bond cleavage to achieve theoretical monomer yields. Strong correlations were observed between the yield of monomeric aromatic compounds and the structural features of lignin, including the contents of ß-O-4 linkages and phenolic hydroxyl groups. Notably, a combined yield of up to 44.1â wt % was obtained from ß-aryl ether rich in native lignin, whereas much lower yields were obtained from technical lignins low in ß-aryl ether content. This work quantitatively demonstrates that the lignin reactivity for acquiring aromatic monomer yields varies depending on the lignin fractionation processes.
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To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention. In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance. We hypothesize that the enzymes required for the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis, could serve as therapeutic targets for cancers. Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM. The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively. One of GAL-012 derivatives GAL-012-2 also demonstrated the inhibitory activity against GALT and UGP2. Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM. Western blot analysis revealed reduced expression of pAKT (Ser473), pAKT (Thr308) by 77% and 72%, respectively in the treated cells. siRNA experiments against the respective genes encoding the pyrophosphorylases were also performed and the results further validated the proposed roles in cancer growth inhibition. Finally, synergistic relationships between GAL-012 and tunicamycin, as well as bortezomib (BTZ) in killing cultured cancer cells were observed, respectively. With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
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Antineoplásicos/química , Antineoplásicos/farmacología , Descubrimiento de Drogas , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , UTP-Hexosa-1-Fosfato Uridililtransferasa/antagonistas & inhibidores , UTP-Hexosa-1-Fosfato Uridililtransferasa/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas/métodos , Técnicas de Inactivación de Genes , Glicosilación , Humanos , Conformación Molecular , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Polisacáridos/metabolismo , UTP-Hexosa-1-Fosfato Uridililtransferasa/genéticaRESUMEN
Intrauterine growth restriction (IUGR) and maternal high-fat diet (HFD) independently predispose offspring to hypertension. In a rat model, IUGR more so than maternal HFD increases arterial stiffness with vascular remodeling as early as postnatal day (PND) 21. The trajectory of such early vascular changes remains unknown. We hypothesized that IUGR would increase blood pressure (BP), arterial stiffness, and markers of ongoing detrimental vascular remodeling in adult rats exposed to a maternal HFD regardless of weaning diet. Adult female rats were fed either a regular diet (RD) or an HFD before mating through lactation. IUGR was induced by uterine artery ligation. Offspring were weaned to either a RD or HFD through PND 60. For both control and IUGR rats, this design resulted in the following three diet groups: offspring from RD dams weaned to a RD and offspring from HFD dams weaned to a RD or to an HFD (IHH). In both males and females, only IHH increased systolic BP, but IUGR and HFD both alone and in combination increased arterial stiffness. Aortas contained fewer but thicker elastin bands in IHH rats and IUGR offspring from dams fed an HFD and weaned to a regular diet. IHH increased aortic lysl oxidase protein. In summary, the PND 21 rat mediators of vascular remodeling from IUGR and maternal HFD normalize by PND 60 while changes in elastin and arterial stiffness persist. We speculate that the longer-term risk of hypertension from dietary mediators is augmented by underlying IUGR-induced structural changes to the extracellular matrix.NEW & NOTEWORTHY We report that a combined insult of intrauterine growth restriction and maternal high-fat diet increases the risk of early cardiovascular pathology both independently and in conjunction with a continued high-fat diet in offspring.
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Aorta Abdominal/fisiopatología , Dieta Alta en Grasa , Retardo del Crecimiento Fetal/fisiopatología , Fenómenos Fisiologicos Nutricionales Maternos , Efectos Tardíos de la Exposición Prenatal , Remodelación Vascular , Rigidez Vascular , Factores de Edad , Animales , Aorta Abdominal/metabolismo , Presión Arterial , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Matriz Extracelular/metabolismo , Femenino , Retardo del Crecimiento Fetal/metabolismo , Masculino , Estado Nutricional , Embarazo , Ratas Sprague-Dawley , Factores SexualesRESUMEN
Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes. Midline cleft defects are present at birth. Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation. To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology. After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes. Ultrasound studies of the course of pregnancy confirmed Pgm2-deficient pups succumb before E9.5. Oral galactose supplementation (9 mg/mL drinking water) did not rescue the lethality. Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content. However, glycomics analyses in serum revealed an abnormal glycosylation pattern in the Pgm2+/- animals, similar to that seen in PGM1-CDG.
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Trastornos Congénitos de Glicosilación/tratamiento farmacológico , Galactosa/administración & dosificación , Genes Letales , Fosfoglucomutasa/deficiencia , Animales , Animales Recién Nacidos , Trastornos Congénitos de Glicosilación/complicaciones , Trastornos Congénitos de Glicosilación/enzimología , Femenino , Glicosilación , Heterocigoto , Homocigoto , Hipoglucemia/complicaciones , Masculino , Ratones , Ratones Noqueados , Enfermedades Musculares/complicaciones , Enfermedades Musculares/patología , FenotipoRESUMEN
The epithelial-specific splicing regulators Esrp1 and Esrp2 are required for mammalian development, including establishment of epidermal barrier functions. However, the mechanisms by which Esrp ablation causes defects in epithelial barriers remain undefined. We determined that the ablation of Esrp1 and Esrp2 impairs epithelial tight junction (TJ) integrity through loss of the epithelial isoform of Rho GTP exchange factor Arhgef11. Arhgef11 is required for the maintenance of TJs via RhoA activation and myosin light chain (MLC) phosphorylation. Ablation or depletion of Esrp1/2 or Arhgef11 inhibits MLC phosphorylation and only the epithelial Arhgef11 isoform rescues MLC phosphorylation in Arhgef11 KO epithelial cells. Mesenchymal Arhgef11 transcripts contain a C-terminal exon that binds to PAK4 and inhibits RhoA activation byArhgef11. Deletion of the mesenchymal-specific Arhgef11 exon in Esrp1/2 KO epithelial cells using CRISPR/Cas9 restored TJ function, illustrating how splicing alterations can be mechanistically linked to disease phenotypes that result from impaired functions of splicing regulators.
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Empalme Alternativo/genética , Células Epiteliales/metabolismo , Proteínas de Unión al ARN/metabolismo , Factores de Intercambio de Guanina Nucleótido Rho/genética , Uniones Estrechas/metabolismo , Alopecia/patología , Animales , Animales Recién Nacidos , Sistemas CRISPR-Cas/genética , Permeabilidad de la Membrana Celular , Exones/genética , Inflamación/patología , Queratinocitos/metabolismo , Mesodermo/metabolismo , Ratones Noqueados , Cadenas Ligeras de Miosina/metabolismo , Fosforilación , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Factores de Intercambio de Guanina Nucleótido Rho/metabolismo , Quinasas p21 Activadas/metabolismo , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
The phenotypic response of bones differing in morphological, compositional, and mechanical traits to an increase in loading during growth is not well understood. We tested whether bones of two inbred mouse strains that assemble differing sets of traits to achieve mechanical homeostasis at adulthood would show divergent responses to voluntary cage-wheel running. Female A/J and C57BL6/J (B6) 4-week-old mice were provided unrestricted access to a standard cage-wheel for 4 weeks. A/J mice have narrow and highly mineralized femora and B6 mice have wide and less mineralized femora. Both strains averaged 2 to 9.5 km of running per day, with the average-distance run between strains not significantly different (p = 0.133). Exercised A/J femora showed an anabolic response to exercise with the diaphyses showing a 2.8% greater total area (Tt.Ar, p = 0.06) and 4.7% greater cortical area (Ct.Ar, p = 0.012) compared to controls. In contrast, exercised B6 femora showed a 6.2% (p < 0.001) decrease in Tt.Ar (p < 0.001) and a 6.7% decrease in Ct.Ar (p = 0.133) compared to controls, with the femora showing significant marrow infilling (p = 0.002). These divergent morphological responses to exercise, which did not depend on the daily distance run, translated to a 7.9% (p = 0.001) higher maximum load (ML) for exercised A/J femora but no change in ML for exercised B6 femora compared to controls. A consistent response was observed for the humeri but not the vertebral bodies. This differential outcome to exercise has not been previously observed in isolated loading or forced treadmill running regimes. Our findings suggest there are critical factors involved in the metabolic response to exercise during growth that require further consideration to understand how genotype, exercise, bone morphology, and whole-bone strength interact during growth. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
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Although food-hoarding animals benefit plant seeds by generating predation pressure on granivorous insects, we lack experimental evidence of whether the tripartite interactions maintain a mutualistic relationship between the third trophic level and primary producers. Relying on the behavior of shelling, Siberian chipmunks (Tamias sibiricus) selectively consumed weevil larvae infested in acorns of Mongolian oak (Quercus mongolica) but chose the non-infested acorns to scatter-hoard. Shelling not only reduced volatile emission from acorns but also decreased cache loss to pilferers, weevil larvae and fungi, allowing T. sibiricus to gain more rewards from their caches. Moreover, shelling by T. sibiricus enhanced acorn germination and seedling establishment of Q. mongolica, possibly due to the diminishment of the negative effects of weevil infestation on acorn viability. Here, we show that both food-hoarding animal T. sibiricus and oak Q. mongolica can be conditionally benefited from selective predation on weevil larvae inside acorns. Our results highlight the need to integrate the mutualisms between the third and first trophic level into the tripartite interaction model. We suggest that more efforts should be made in the tripartite interactions of food-hoarding animals, seeds and granivorous insects.