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1.
Brain Behav Immun ; 117: 155-166, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38215888

RESUMEN

A "switch" in the metabolic pattern of microglia is considered to be required to meet the metabolic demands of cell survival and functions. However, how metabolic switches regulate microglial function remains controversial. We found here that exposure to amyloid-ß triggers microglial inflammation accompanied by increasing GAPDH levels. The increase of GAPDH, a glycolysis enzyme, leads to the reduced release of interferon-γ (IFN-γ) from inflammatory microglia. Such alternation is translational and is regulated by the binding of glycolysis enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to IFN-γ mRNA. GAPDH, by engaging/disengaging glycolysis and through influencing IFN-γ expression, regulates microglia functions, including phagocytosis and cytokine production. Phosphoglycerate dehydrogenase (PHGDH), screened from different state microglia by metabolomics combined with METARECON analysis, is a metabolic enzyme adjacent downstream of GAPDH and synthesizes serine on the collateral pathway derived from glycolysis. Polarization of microglial with PHGDH as a metabolic checkpoint can be bidirectionally regulated by adding IL-4 or giving PHGDH inhibitors. Therefore, regulation of metabolic enzymes not only reprograms metabolic patterns, but also manipulates microglia functions. Further study should be performed to explore the mechanism of metabolic checkpoints in human microglia or more in vivo animal experiments, and may expand to the effects of various metabolic substrates or enzyme, such as lipids and amino acids, on the functions of microglia.


Asunto(s)
Microglía , Fosfoglicerato-Deshidrogenasa , Animales , Humanos , Fosfoglicerato-Deshidrogenasa/genética , Interferón gamma , Multiómica , Gliceraldehído-3-Fosfato Deshidrogenasas/genética
2.
Angew Chem Int Ed Engl ; 63(28): e202406588, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38664822

RESUMEN

The selective oxidation of benzylic C-H bonds is a pivotal transformation in organic synthesis. Undoubtedly, achieving efficient and highly selective aerobic oxidation of methylarenes to benzaldehydes has been highly challenging due to the propensity of benzaldehyde to undergo overoxidation under typical aerobic conditions. Herein, we propose an innovative approach to address this issue by leveraging electrocatalytic processes, facilitated by ion-pair mediators [Ph3C]+[B(C6F5)4]-. By harnessing the power of electrochemistry, we successfully demonstrated the effectiveness of our strategy, which enables the selective oxidation of benzylic C-H bonds in benzylic molecules and toluene derivatives. Notably, our approach exhibited high efficiency, excellent selectivity, and compatibility with various functional groups, underscoring the broad applicability of our methodology.

3.
Opt Express ; 31(20): 32925-32934, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37859084

RESUMEN

Development of miniature two-photon microscopy (m2PM) has made it possible to observe fine structure and activity of neurons in the brain of freely moving animals. However, the imaging field-of-view of existing m2PM is still significantly smaller than that of miniature single-photon microscopy. Here we report that, through the design of low-magnification objective, large field-of-view scan lens and small tilt angle microscanner, a 2.5-g m2PM achieved a field-of-view of 1000 × 788 µm2, comparable to that of a typical single-photon miniscope. We demonstrated its capability by imaging neurons, dendrites and spines in the millimeter field-of-view, and simultaneous recording calcium activities, through a gradient-index lens, of approximately 400 neurons in the dorsal hippocampal CA1 in a freely moving mouse. Integrated with a detachable 1.2-g fast z-scanning module, it enables a 1000 × 788 × 500 µm3 volumetric neuronal imaging in the cerebral cortex. Thus, millimeter FOV m2PM provides a powerful tool for deciphering neuronal population dynamics in experimental paradigms allowing for animal's free movement.


Asunto(s)
Encéfalo , Microscopía , Ratones , Animales , Microscopía/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Cabeza , Neuronas/fisiología , Neuroimagen
4.
J Endovasc Ther ; : 15266028231168351, 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37144300

RESUMEN

PURPOSE: We aim to quantify multiaxial cardiac pulsatility-induced deformation of the thoracic aorta after ascending thoracic endovascular aortic repair (TEVAR) as a part of the GORE ARISE Early Feasibility Study. MATERIALS AND METHODS: Fifteen patients (7 females and 8 males, age 73±9 years) with ascending TEVAR underwent computed tomography angiography with retrospective cardiac gating. Geometric modeling of the thoracic aorta was performed; geometric features including axial length, effective diameter, and centerline, inner surface, and outer surface curvatures were quantified for systole and diastole; and pulsatile deformations were calculated for the ascending aorta, arch, and descending aorta. RESULTS: From diastole to systole, the ascending endograft exhibited straightening of the centerline (0.224±0.039 to 0.217±0.039 cm-1, p<0.05) and outer surface (0.181±0.028 to 0.177±0.029 cm-1, p<0.05) curvatures. No significant changes were observed for inner surface curvature, diameter, or axial length in the ascending endograft. The aortic arch did not exhibit any significant deformation in axial length, diameter, or curvature. The descending aorta exhibited small but significant expansion of effective diameter from 2.59±0.46 to 2.63±0.44 cm (p<0.05). CONCLUSION: Compared with the native ascending aorta (from prior literature), ascending TEVAR damps axial and bending pulsatile deformations of the ascending aorta similar to how descending TEVAR damps descending aortic deformations, while diametric deformations are damped to a greater extent. Downstream diametric and bending pulsatility of the native descending aorta was muted compared with that in patients without ascending TEVAR (from prior literature). Deformation data from this study can be used to evaluate the mechanical durability of ascending aortic devices and inform physicians about the downstream effects of ascending TEVAR to help predict remodeling and guide future interventional strategies. CLINICAL IMPACT: This study quantified local deformations of both stented ascending and native descending aortas to reveal the biomechanical impact of ascending TEVAR on the entire thoracic aorta, and reported that the ascending TEVAR muted cardiac-induced deformation of the stented ascending aorta and native descending aorta. Understanding of in vivo deformations of the stented ascending aorta, aortic arch and descending aorta can inform physicians about the downstream effects of ascending TEVAR. Notable reduction of compliance may lead to cardiac remodeling and long-term systemic complications. This is the first report which included dedicated deformation data regarding ascending aortic endograft from clinical trial.

5.
J Nanobiotechnology ; 21(1): 281, 2023 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-37598162

RESUMEN

BACKGROUND: Iron sulfide nanomaterials have been successfully employed as therapeutic agents for bacterial infection therapy and catalytic-ferroptosis synergistic tumor therapy due to their unique structures, physiochemical properties, and biocompatibility. However, biomedical research and understanding of the biological functions of iron sulfides are insufficient, and how iron sulfide nanomaterials affect reactive oxygen species (ROS) in diseases remains unknown. Acute kidney injury (AKI) is associated with high levels of ROS, and therefore nanomedicine-mediated antioxidant therapy has emerged as a novel strategy for its alleviation. RESULTS: Here, mackinawite nanozymes were synthesized from glutathione (GSH) and iron ions (Fe3+) (denoted as GFeSNs) using a hydrothermal method, and then evaluated as ROS scavengers for ROS-related AKI treatment. GFeSNs showed broad-spectrum ROS scavenging ability through synergistic interactions of multiple enzymes-like and hydrogen polysulfide-releasing properties. Furthermore, both in vitro and in vivo experiments demonstrated that GFeSNs exhibited outstanding cytoprotective effects against ROS-induced damage at extremely low doses and significantly improved treatment outcomes in AKI. CONCLUSIONS: Given the synergetic antioxidant properties and high biocompatibility, GFeSNs exhibit great potential for the treatment of AKI and other ROS-associated diseases.


Asunto(s)
Lesión Renal Aguda , Antioxidantes , Animales , Antioxidantes/farmacología , Especies Reactivas de Oxígeno , Lesión Renal Aguda/tratamiento farmacológico , Hierro , Peces , Glutatión
6.
J Allergy Clin Immunol ; 149(4): 1225-1241, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35074422

RESUMEN

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic and contagious coronavirus that caused a global pandemic with 5.2 million fatalities to date. Questions concerning serologic features of long-term immunity, especially dominant epitopes mediating durable antibody responses after SARS-CoV-2 infection, remain to be elucidated. OBJECTIVE: We aimed to dissect the kinetics and longevity of immune responses in coronavirus disease 2019 (COVID-19) patients, as well as the epitopes responsible for sustained long-term humoral immunity against SARS-CoV-2. METHODS: We assessed SARS-CoV-2 immune dynamics up to 180 to 220 days after disease onset in 31 individuals who predominantly experienced moderate symptoms of COVID-19, then performed a proteome-wide profiling of dominant epitopes responsible for persistent humoral immune responses. RESULTS: Longitudinal analysis revealed sustained SARS-CoV-2 spike protein-specific antibodies and neutralizing antibodies in COVID-19 patients, along with activation of cytokine production at early stages after SARS-CoV-2 infection. Highly reactive epitopes that were capable of mediating long-term antibody responses were shown to be located at the spike and ORF1ab proteins. Key epitopes of the SARS-CoV-2 spike protein were mapped to the N-terminal domain of the S1 subunit and the S2 subunit, with varying degrees of sequence homology among endemic human coronaviruses and high sequence identity between the early SARS-CoV-2 (Wuhan-Hu-1) and current circulating variants. CONCLUSION: SARS-CoV-2 infection induces persistent humoral immunity in COVID-19-convalescent individuals by targeting dominant epitopes located at the spike and ORF1ab proteins that mediate long-term immune responses. Our findings provide a path to aid rational vaccine design and diagnostic development.


Asunto(s)
COVID-19 , Anticuerpos Antivirales , Epítopos , Humanos , Inmunidad Humoral , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus
7.
BMC Cancer ; 22(1): 1042, 2022 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-36199068

RESUMEN

OBJECTIVE: Pancreatic adenocarcinoma (PAAD) is a leading cause of cancer-related mortality in adults. Syndecan-4 (SDC4) is involved in cancer pathogenesis. Therefore, this study aimed to explore the expression and clinical significance of SDC4 in PAAD. METHODS: Differentially expressed genes (DEGs) between PAAD and normal pancreas were screened from the GTEx and TCGA databases, and the correlationship between the DEGs and prognosis were analyzed. The prognostic value of the screened SDC4, SERPINE1, and SLC2A1 was evaluated using the Kaplan-Meier curve and SDC4 was subsequently selected as the better candidate. Also, SDC4 expression was analyzed in PAAD tissues, the other risk factors affecting postoperative survival were analyzed using Cox regression analysis, and SDC4-mediated pathways enrichment was identified by GSVA and GSEA. SDC4 expression in PAAD tissues and adjacent normal tissues of selected PAAD patients was detected by RT-qPCR and immunohistochemistry. The correlation between SDC4 and clinical features was evaluated by the χ2 test. RESULTS: SDC4 was highly expressed in PAAD tissues. Elevated SDC4 was correlated with reduced overall survival. SDC4 enrichment pathways included spliceosome function, proteasome activity, pentose phosphate pathway, base excision repair, mismatch repair, DNA replication, oxidative phosphorylation, mitotic spindle formation, epithelial-mesenchymal transition, and G2M checkpoints. SDC4 was elevated in PAAD tissues of PAAD patients compared with adjacent normal tissues. High SDC4 expression was related to metastatic differentiation, TNM stage, lymphatic metastasis, and lower 3-year survival rate. SDC4 was an independent risk factor affecting postoperative survival. CONCLUSION: SDC4 was highly expressed in PAAD and was related to clinicopathological features and poor prognosis, which might be an important index for PAAD early diagnosis and prognosis.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pancreáticas/patología , Pronóstico , Complejo de la Endopetidasa Proteasomal/genética , Sindecano-4/genética , Sindecano-4/metabolismo , Neoplasias Pancreáticas
8.
Sensors (Basel) ; 22(17)2022 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-36080908

RESUMEN

Automatic modulation classification (AMC) plays a fundamental role in common communication systems. Existing clustering models typically handle fewer modulation types with lower classification accuracies and more computational resources. This paper proposes a hierarchical self-organizing map (SOM) based on a feature space composed of high-order cumulants (HOC) and amplitude moment features. This SOM with two stacked layers can identify intrinsic differences among samples in the feature space without the need to set thresholds. This model can roughly cluster the multiple amplitude-shift keying (MASK), multiple phase-shift keying (MPSK), and multiple quadrature amplitude keying (MQAM) samples in the root layer and then finely distinguish the samples with different orders in the leaf layers. We creatively implement a discrete transformation method based on modified activation functions. This method causes MQAM samples to cluster in the leaf layer with more distinct boundaries between clusters and higher classification accuracies. The simulation results demonstrate the superior performance of the proposed hierarchical SOM on AMC problems when compared with other clustering models. Our proposed method can manage more categories of modulation signals and obtain higher classification accuracies while using fewer computational resources.


Asunto(s)
Algoritmos , Análisis por Conglomerados , Simulación por Computador
9.
J Am Chem Soc ; 143(30): 11602-11610, 2021 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-34291644

RESUMEN

Herein we report a chromium-catalyzed allylic defluorinative ketyl olefin coupling between aldehydes and α-trifluoromethyl alkenes, which provides novel and efficient access to diverse gem-difluorohomoallylic alcohols. Remarkably, the high chemoselectivity of this reaction enables the conversion of the formyl moiety in the presence of various easily reducible functionalities including ketone, organohalides, aziridine, sulfone, alkyne, and unactivated alkene. The utility of this method is demonstrated by various simple derivatizations of the attached hydroxyl group of the coupling products. The preliminary mechanistic investigations suggest a reaction pathway with a rate-limiting C-C forming step followed by facile ß-fluoro elimination.

10.
Br J Nutr ; 126(5): 652-662, 2021 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-33222701

RESUMEN

Nutrition in early life has a long-term influence on later health. In order to the explore effects of in ovo feeding (IOF) of vitamin C on splenic development, splenic metabolism and apoptosis were detected in embryo, adult chickens and in vitro. A total of 360 fertile eggs were selected and randomly assigned to control (CON) and vitamin C (VC) groups which were injected with saline and vitamin C on embryonic day 11, respectively. Functional enrichment of differentially expressed genes by transcriptome on embryonic day 19 suggested that purine nucleotide metabolism might be a potential pathway for the IOF of vitamin C to regulate spleen development. Additionally, the IOF of vitamin C significantly increased splenic vitamin C content on post-hatch day 21. Meanwhile, the splenic expression of adenosine deaminase, serine/threonine kinase 1 and proliferating cell nuclear antigen was down-regulated, whereas the expression of cysteinyl aspartate specific proteinase 9 was up-regulated in the VC group. On post-hatch day 42, the IOF of vitamin C significantly down-regulated the splenic expression of B-cell lymphoma 2 and increased the mRNA level of cysteinyl aspartate specific proteinase 9. The IOF of vitamin C could regulate the expression of genes related to adenylate metabolism and increased the apoptosis rate in vitro, which is consistent with the result in vivo. In conclusion, the IOF of vitamin C regulated splenic development and maturation by affecting purine nucleotide metabolism pathway and promoting apoptosis.


Asunto(s)
Apoptosis , Ácido Ascórbico , Pollos , Nucleótidos de Purina/metabolismo , Bazo/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Ácido Ascórbico/administración & dosificación , Péptido Hidrolasas , Vitaminas/administración & dosificación
11.
Br J Nutr ; 124(9): 903-911, 2020 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-32517823

RESUMEN

This study aimed to evaluate the effect of in ovo feeding (IOF) of vitamin C at embryonic age 11 (E11) on post-hatch performance, immune status and DNA methylation-related gene expression in broiler chickens. A total of 240 Arbor Acres breeder eggs (63 (sem 0·5) g) were randomly divided into two groups: normal saline and vitamin C (VC) groups. After incubation, newly hatched chicks from each group were randomly divided into six replicates with ten chicks per replicate. Hatchability, average daily feed intake (D21-42 and D1-42), and average daily gain and feed conversion ratio (D1-21) were improved by vitamin C treatment (P < 0·05). IOF of vitamin C increased vitamin C content (D1), total antioxidant capacity (D42), IgA (D1), IgM (D1 and D21), stimulation index for T lymphocyte (D35) and lysozyme activity (D21) in plasma (P < 0·05). On D21, vitamin C increased the splenic expression of IL-4 and DNMT1 and decreased IL-1ß, Tet2, Tet3 and Gadd45ß expression (P < 0·05). On D42, vitamin C increased the splenic expression of IL-4 and DNMT3A and decreased IFN-γ, Tet3, MBD4 and TDG expression (P < 0·05). In conclusion, the vitamin C via in ovo injection can be absorbed by broiler's embryo and IOF of vitamin C at E11 improves the post-hatch performance and immune status and, to some extent, the antioxidant capacity of broiler chickens. The expression of enzyme-related DNA methylation and demethylation indicates that the level of DNA methylation may increase in spleen in the VC group and whether the fluctuating expression of pro- and anti-inflammatory cytokines is related to DNA methylation change remained to be further investigated.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales/inmunología , Ácido Ascórbico/administración & dosificación , Metilación de ADN/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Óvulo/efectos de los fármacos , Fenómenos Fisiológicos Nutricionales de los Animales/genética , Animales , Antioxidantes/metabolismo , Embrión de Pollo , Pollos , Citocinas/metabolismo , Huevos , Bazo/metabolismo
12.
New Phytol ; 221(4): 1983-1997, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30339276

RESUMEN

Molybdenum (Mo) is an essential micronutrient for most living organisms, including humans. Cereals such as rice (Oryza sativa) are the major dietary source of Mo. However, little is known about the genetic basis of the variation in Mo content in rice grain. We mapped a quantitative trait locus (QTL) qGMo8 that controls Mo accumulation in rice grain by using a recombinant inbred line population and a backcross introgression line population. We identified a molybdate transporter, OsMOT1;1, as the causal gene for this QTL. OsMOT1;1 exhibits transport activity for molybdate, but not sulfate, when heterogeneously expressed in yeast cells. OsMOT1;1 is mainly expressed in roots and is involved in the uptake and translocation of molybdate under molybdate-limited condition. Knockdown of OsMOT1;1 results in less Mo being translocated to shoots, lower Mo concentration in grains and higher sensitivity to Mo deficiency. We reveal that the natural variation of Mo concentration in rice grains is attributed to the variable expression of OsMOT1;1 due to sequence variation in its promoter. Identification of natural allelic variation in OsMOT1;1 may facilitate the development of rice varieties with Mo-enriched grain for dietary needs and improve Mo nutrition of rice on Mo-deficient soils.


Asunto(s)
Grano Comestible/genética , Grano Comestible/metabolismo , Variación Genética , Proteínas de Transporte de Membrana/genética , Molibdeno/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Alelos , Arabidopsis/genética , Transporte Biológico/efectos de los fármacos , Clonación Molecular , Grano Comestible/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Genes de Plantas , Proteínas de Transporte de Membrana/metabolismo , Molibdeno/farmacología , Mutación/genética , Fenotipo , Proteínas de Plantas/metabolismo , Sitios de Carácter Cuantitativo/genética , Saccharomyces cerevisiae/metabolismo
13.
J Sep Sci ; 42(10): 1915-1929, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30900299

RESUMEN

A facile and sensitive multi-residue detection approach of pressurized liquid extraction following high-performance liquid chromatography tandem mass spectrometry was established to detect the residues of adrenergic drugs, steroids, sedative, colorant and antioxidant in feed. The conditions employed for pressurized liquid extraction involved acetonitrile/ethyl acetate (1:1, v/v) as the extracting solvent, the temperature 80°C, two cycles and a static time of 10 min. The extraction was followed by a solid-phase extraction clean-up step. The separation of samples was done by C18 column with the mobile phase of 5 mM ammonium acetate solution and acetonitrile with 0.1% formic acid. The limits of quantification ranged from 0.03 to 1 µg/kg, limits of detection were in a range of 0.01-0.5 µg/kg, and average recoveries were 70.4-98.6%. The pressurized liquid extraction procedure was optimized and overall method was validated in terms of sensitivity, linearity, selectivity, matrix effect, accuracy, recovery and stability of the target drugs in the pressurized liquid extraction extracts solution. The screening method was proved to be fast, selective, accurate and sensitive for screening drugs.


Asunto(s)
Adrenérgicos/análisis , Alimentación Animal/análisis , Antioxidantes/análisis , Colorantes/análisis , Hipnóticos y Sedantes/análisis , Esteroides/análisis , Acetatos/química , Animales , Fraccionamiento Químico , Cromatografía Líquida de Alta Presión , Formiatos/análisis , Límite de Detección , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Extracción en Fase Sólida , Solventes , Porcinos , Espectrometría de Masas en Tándem
14.
Biol Proced Online ; 18: 18, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27807400

RESUMEN

Aqueous two-phase system (ATPS) is a liquid-liquid fractionation technique and has gained an interest because of great potential for the extraction, separation, purification and enrichment of proteins, membranes, viruses, enzymes, nucleic acids and other biomolecules both in industry and academia. Although, the partition behavior involved in the method is complex and difficult to predict. Current research shows that it has also been successfully used in the detection of veterinary drug residues in food, separation of precious metals, sewage treatment and a variety of other purposes. The ATPS is able to give high recovery yield and is easily to scale up. It is also very economic and environment friendly method. The aim of this review is to overview the basics of ATPS, optimization and its applications.

15.
J Sep Sci ; 39(13): 2584-94, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27145483

RESUMEN

A comprehensive strategy combining a quantitative method was developed for 30 banned drugs including ß-agonists, hormones, glucocorticoid and psychiatric drugs in swine and chicken feeds. This rapid, simple and effective extraction method was based on matrix solid-phase dispersion and electrospray ionization tandem mass spectrometry. The quantitative method was validated after previous statistical optimization of the main parameters of matrix solid-phase dispersion. The limit of quantification of dopamine hydrochloride, chlormadinone acetate, melengestrol acetate, testosterone propionate, nandrolone and midazolam was 2 µg/kg and that of the other 24 drugs was 1 µg/kg. The recoveries of ß-agonists, hormones, glucocorticoid and psychiatric drugs spiked in swine and chicken feeds at a concentration range of 1-8 µg/kg were above 70.1% with inter-day relative standard deviations less than 15.8%. The analytical strategy was applied to 100 feed samples collected from a local market in Wuhan (China). Clenbuterol, ractopamine and melengestrol acetate were identified and quantified at the level 0.2∼3.5 µg/kg. The rapid and reliable method can be used to efficiently separate, characterize and quantify the residues of 30 banned drugs in swine and chicken feeds with advantages of simple pretreatment and environmental friendly nature.


Asunto(s)
Agonistas Adrenérgicos beta/análisis , Glucocorticoides/análisis , Hormonas/análisis , Psicotrópicos/análisis , Cromatografía Líquida de Alta Presión , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem
16.
Nucleic Acids Res ; 42(22): 13969-80, 2014 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-25428370

RESUMEN

Numerous eukaryotic genes are alternatively spliced. Recently, deep transcriptome sequencing has skyrocketed proportion of alternatively spliced genes; over 95% human multi-exon genes are alternatively spliced. One fundamental question is: are all these alternative splicing (AS) events functional? To look into this issue, we studied the most common form of alternative 5' splice sites-GYNNGYs (Y = C/T), where both GYs can function as splice sites. Global analyses suggest that splicing noise (due to stochasticity of splicing process) can cause AS at GYNNGYs, evidenced by higher AS frequency in non-coding than in coding regions, in non-conserved than in conserved genes and in lowly expressed than in highly expressed genes. However, ∼20% AS GYNNGYs in humans and ∼3% in mice exhibit tissue-dependent regulation. Consistent with being functional, regulated GYNNGYs are more conserved than unregulated ones. And regulated GYNNGYs have distinctive sequence features which may confer regulation. Particularly, each regulated GYNNGY comprises two splice sites more resembling each other than unregulated GYNNGYs, and has more conserved downstream flanking intron. Intriguingly, most regulated GYNNGYs may tune gene expression through coupling with nonsense-mediated mRNA decay, rather than encode different proteins. In summary, AS at GYNNGY 5' splice sites is primarily splicing noise, and secondarily a way of regulation.


Asunto(s)
Empalme Alternativo , Sitios de Empalme de ARN , Animales , Secuencia de Bases , Secuencia Conservada , Humanos , Macaca mulatta , Ratones , Especificidad de Órganos
17.
Mol Biol Evol ; 30(12): 2588-601, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24023392

RESUMEN

In female mammals most X-linked genes are subject to X-inactivation. However, in humans some X-linked genes escape silencing, these escapees being candidates for the phenotypic aberrations seen in polyX karyotypes. These escape genes have been reported to be under stronger purifying selection than other X-linked genes. Although it is known that escape from X-inactivation is much more common in humans than in mice, systematic assays of escape in humans have to date employed only interspecies somatic cell hybrids. Here we provide the first systematic next-generation sequencing analysis of escape in a human cell line. We analyzed RNA and genotype sequencing data obtained from B lymphocyte cell lines derived from Europeans (CEU) and Yorubans (YRI). By replicated detection of heterozygosis in the transcriptome, we identified 114 escaping genes, including 76 not previously known to be escapees. The newly described escape genes cluster on the X chromosome in the same chromosomal regions as the previously known escapees. There is an excess of escaping genes associated with mental retardation, consistent with this being a common phenotype of polyX phenotypes. We find both differences between populations and between individuals in the propensity to escape. Indeed, we provide the first evidence for there being both hyper- and hypo-escapee females in the human population, consistent with the highly variable phenotypic presentation of polyX karyotypes. Considering also prior data, we reclassify genes as being always, never, and sometimes escape genes. We fail to replicate the prior claim that genes that escape X-inactivation are under stronger purifying selection than others.


Asunto(s)
Expresión Génica , Genes Ligados a X , Discapacidad Intelectual/genética , Inactivación del Cromosoma X , Animales , Pueblo Asiatico/genética , Línea Celular , Evolución Molecular , Femenino , Variación Genética , Humanos , Masculino , Ratones , Tasa de Mutación , Fenotipo , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ARN , Población Blanca/genética , Cromosoma X
18.
Cytogenet Genome Res ; 143(4): 221-4, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25227289

RESUMEN

We report on a patient with a 47,XXY karyotype who presents a normal female phenotype, which is an extremely rare observation worldwide. The patient is infertile. Type B ultrasound scans and other tests suggested that her ovaries had completely failed. Microsatellite DNA marker analysis revealed that the 2 X chromosomes were derived from her mother and that this abnormality was caused by non-disjunction of the maternal X chromosomes during meiosis II. Copy number variation analysis identified 2 large de novo deletions in her Y chromosome. Remarkably, one of the deleted regions includes the SRY gene locus, which might explain her female phenotype. However, the genetic mechanism of her ovarian failure remains unclear. This paper is the first report of a 47,XXY female with ovarian failure.


Asunto(s)
Síndrome de Klinefelter/diagnóstico , Insuficiencia Ovárica Primaria/diagnóstico , Adulto , Cromosomas Humanos Y/genética , Femenino , Eliminación de Gen , Genes sry , Humanos , Síndrome de Klinefelter/genética , Técnicas de Diagnóstico Molecular , Linaje , Polimorfismo de Nucleótido Simple , Insuficiencia Ovárica Primaria/genética
19.
Data Brief ; 53: 110049, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38317731

RESUMEN

This data article presents experimental and numerical datasets for eight fixed-base, single storey, unbraced high strength steel welded I-section frames subjected to in-plane horizontal and vertical loading. A detailed description of the full-scale frame testing programme is provided in the related research article 'Benchmark tests on high strength steel frames'. The experimental dataset can be used to steer future research in full-scale structural testing and provide benchmark results that are suitable for the validation of finite element models and the development of system-level design approaches. In addition to the benchmark experimental frame data, all necessary details and data for shell finite element (FE) model validation using geometrically and materially nonlinear analysis (GMNIA) is presented. The general purpose FE software Abaqus was used. The dataset can be used as an illustrative example of GMNIA validation in accordance with EN 1993-1-14 with all relevant data for reproducibility provided.

20.
Poult Sci ; 103(2): 103282, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38147728

RESUMEN

Growing evidence of fecal microbiota transplantation (FMT) and fecal virus transplantation (FVT) provides a possibility to regulate animal health, whereas little is known about the impact of the 2 methods. This study aimed to investigate the effects of gut microbes on jejunal function in healthy broiler chickens, with the objective of establishing a theoretical basis for the application of FMT and FVT. Cecal feces from 28-day-old AA broilers were collected to prepare gavage juice for FMT and FVT. FMT for Group FM, FVT for group FV and PBS gavage for group CON, continuously treated for 6 days start at 5-day-old chicks. Samples were collected at d 11 and d 21. The results showed that the treatment d 2 and the overall fecal score in treatment groups were significantly lower than CON group (P < 0.05). The jejunum morphology showed that FMT increased crypt depth, decreased villus height, V/C (P < 0.05) and FVT increased villus height (P < 0.05) at d 11. At d 21, villus height and crypt depth significantly higher (P < 0.05) in group FM and group FV. The expression of Claudin1, Occludin, ZO2, and Muc2 in the FV group was significantly increased (P < 0.05) at 11-day-old. FMT increased the secretion of sIgA at 11-day-old, and this influence lasted up to 21-day-old (P < 0.05). At 11-day-old, the expression of b0+AT of basic amino acid transport carrier and chymotrypsin activity (P < 0.05) had a significant correlation. At 21 d of age, FVT significantly increased the expression of PepT1 and SGLT1 (P < 0.05). At 11-day-old, FM group showed significantly higher faith pd index (P = 0.004) and Shannon index (P = 0.037), and separated from FV and CON according to PCoA. Among differentiating bacteria, Bacteroides significantly enriched (P < 0.05) in group FM, which positively correlated with the expression of ZO2, Muc2, Occludin, and Claudin1; R_Ruminococcus, L_Ruminococcus, Butyricicoccuss significantly enriched (P < 0.05) in group CON, which significantly higher than processing groups, R_Ruminococcus and L_Ruminococcus negatively correlated with the expression of Occludin (P < 0.05), and R_Ruminococcus, Butyricicoccus negatively correlated with the expression of Claudin1 (P < 0.05). At 21-day-old, PCoA based on Bray-Curtis shows that microbes taxa of 3 groups are isolated with each other and treatment groups were significant different with CON group based on Unweighted UniFrac and weighted UniFrac. The expression of PepT1 was significantly negatively (P < 0.05) correlated with Ruminococcus, and the expression of sIgA was significantly negatively (P < 0.05) correlated with Parabacteroides. In conclusion, FMT regulated intestinal flora rapidly, while it had little effect on intestinal function and a higher potential damaging risk on jejunal. FVT regulated intestinal flora structure softer, improved tight junction expression, but the mechanism of action needs further exploration.


Asunto(s)
Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Animales , Trasplante de Microbiota Fecal/veterinaria , Pollos/microbiología , Ocludina , Inmunoglobulina A Secretora
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