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We present a data-driven method to learn stochastic reduced models of complex systems that retain a state-dependent memory beyond the standard generalized Langevin equation with a homogeneous kernel. The constructed model naturally encodes the heterogeneous energy dissipation by jointly learning a set of state features and the non-Markovian coupling among the features. Numerical results demonstrate the limitation of the standard generalized Langevin equation and the essential role of the broadly overlooked state-dependency nature in predicting molecule kinetics related to conformation relaxation and transition.
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One important problem in constructing the reduced dynamics of molecular systems is the accurate modeling of the non-Markovian behavior arising from the dynamics of unresolved variables. The main complication emerges from the lack of scale separations, where the reduced dynamics generally exhibits pronounced memory and non-white noise terms. We propose a data-driven approach to learn the reduced model of multi-dimensional resolved variables that faithfully retains the non-Markovian dynamics. Different from the common approaches based on the direct construction of the memory function, the present approach seeks a set of non-Markovian features that encode the history of the resolved variables and establishes a joint learning of the extended Markovian dynamics in terms of both the resolved variables and these features. The training is based on matching the evolution of the correlation functions of the extended variables that can be directly obtained from the ones of the resolved variables. The constructed model essentially approximates the multi-dimensional generalized Langevin equation and ensures numerical stability without empirical treatment. We demonstrate the effectiveness of the method by constructing the reduced models of molecular systems in terms of both one-dimensional and four-dimensional resolved variables.
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Cadeias de MarkovRESUMO
A hallmark of meso-scale interfacial fluids is the multi-faceted, scale-dependent interfacial energy, which often manifests different characteristics across the molecular and continuum scale. The multi-scale nature imposes a challenge to construct reliable coarse-grained (CG) models, where the CG potential function needs to faithfully encode the many-body interactions arising from the unresolved atomistic interactions and account for the heterogeneous density distributions across the interface. We construct the CG models of both single- and two-component polymeric fluid systems based on the recently developed deep coarse-grained potential [Zhang et al., J. Chem. Phys. 149, 034101 (2018)] scheme, where each polymer molecule is modeled as a CG particle. By only using the training samples of the instantaneous force under the thermal equilibrium state, the constructed CG models can accurately reproduce both the probability density function of the void formation in bulk and the spectrum of the capillary wave across the fluid interface. More importantly, the CG models accurately predict the volume-to-area scaling transition for the apolar solvation energy, illustrating the effectiveness to probe the meso-scale collective behaviors encoded with molecular-level fidelity.
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BACKGROUND: With reduced balance and mobility, older patients with stroke are more susceptible to fear of falling (FOF). A maladaptive form of FOF can cause excessive activity restriction, poor balance, and recurrent falls, forming a self-reinforcing vicious cycle. This study applied and adapted the FOF model to investigate the interaction between FOF and fall risk in older stroke patients. METHODS: A cross-sectional study was conducted among 302 older stroke patients aged 60 and over. All participants were invited to complete the FOF, fall risk, physical activity, and balance tests, which were measured by the Falls Efficacy Scale International (FES-I), Self-Rated Fall Risk Questionnaire (FRQ), the long-form International Physical Activity Questionnaire (IPAQ-LF) and the Four-Stage Balance Test (FSBT) respectively. Data were analyzed using structural equation modeling. RESULTS: The mean age of the respondents was 68.62 ± 7.62 years; 8.94% reported a high level of FOF, and 18.21% reported a moderate level of FOF. The structural equation model showed that FOF was directly associated with fall risk (ß=-0.38, p < 0.001), and was indirectly associated with fall risk via physical activity (ß=-0.075, p < 0.05) and balance ability (ß=-0.123, p < 0.05). Depression (ß=-0.47, p < 0.001), fall history (ß=-0.13, p < 0.05), and female sex (ß=-0.16, p < 0.05) affected FOF, while anxiety was not associated with FOF. CONCLUSIONS: The increased risk of falling in older stroke patients results from a maladaptive FOF affected by depression, fall history, poor balance ability, and limited physical activity. Our results suggest that greater attention should be paid to FOF during stroke recovery and fall prevention. A multifaced intervention program encompassing physiological and psychological factors should be designed to address FOF and prevent falls.
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Medo , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Medo/psicologia , Estudos Transversais , Análise de Classes Latentes , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Vida IndependenteRESUMO
The relationship between large conductance calcium activated potassium channel (BKCa) and vascular lesions in type 2 diabetes mellitus (T2DM) was investigated by observing vascular reactivity of thoracic aorta and mesenteric artery and the current changes of BKCa in vascular smooth muscle cells (VSMCs). The thoracic aorta and mesenteric artery of T2DM rats were isolated, the whole cell perforated patch clamp experiment and single channel patch clamp experiment of acute enzyme separation of thoracic aorta and mesenteric artery smooth muscle cells were performed to measure the membrane capacitance and the amplitude of macro current. And the vascular ring experiment was performed to observe the change of relaxation percentage. The results showed that the amplitude of BKCa current in vascular smooth muscle cells of diabetic rats was higher than that of the control group. The channel current had outward rectifying characteristics. BKCa is related to vascular reactivity and smooth muscle relaxation in T2DM rats. The opening probability of BKCa in VSMCs of diabetic rats was significantly increased. This study suggests that BKCa may be a new target for diabetic vascular disease.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Aorta Torácica , Diabetes Mellitus Experimental/metabolismo , Artérias Mesentéricas/metabolismo , Músculo Liso Vascular , Miócitos de Músculo Liso , RatosRESUMO
OBJECTIVES: Guanylate cyclase-C (GC-C) agonists, which increase intestinal secretion and accelerate transit, are used to treat chronic constipation and constipation-predominant irritable bowel syndrome and are being evaluated for pediatric use. Prior studies suggest GC-C receptor density may be higher in young children, potentially amplifying GC-C agonism with treatment implications. We aimed to quantitate duodenal and colonic GC-C mRNA expression in children. METHODS: Mucosal biopsies were obtained from subjects aged 6âmonths to 18âyears during clinically indicated upper, that is, esophago-gastro-duodenal, and/or colonic endoscopy. Tissue samples without histologic abnormalities were grouped by subject age (<24âmonths, 24âmonths to <6âyears, 6 to <12âyears, and 12 to <18âyears) and analyzed for GC-C mRNA expression by qPCR. The relationship between GC-C mRNA levels and age was modeled using regression analyses. RESULTS: Ninety-nine subjects underwent upper endoscopy/colonoscopy; 93 had evaluable samples. Mean relative GC-C mRNA expression was 2.36 (range 2.21-2.46) for duodenal samples and 1.56 (range 1.22-1.91) for colonic samples. Predicted and observed normalized GC-C mRNA expression in each region were comparable among age groups. Pooled expression by region demonstrated lower expression in colonic versus duodenal samples. CONCLUSIONS: Uniform levels of GC-C mRNA expression were detected in children aged >6âmonths in the duodenum and >12âmonths in the colon. Higher expression was observed in all age groups in duodenal versus colonic samples, indicating regional variability in GC-C receptor density. These data are reassuring for further studies of GC-C agonists in children.
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Colo , Duodeno , Guanilato Ciclase , Mucosa Intestinal , Adolescente , Criança , Pré-Escolar , Colo/metabolismo , Duodeno/metabolismo , Guanilato Ciclase/metabolismo , Humanos , Lactente , Mucosa Intestinal/metabolismo , RNA Mensageiro/metabolismoRESUMO
Plant growth and architecture is regulated by the polar distribution of the hormone auxin. Polarity and flexibility of this process is provided by constant cycling of auxin transporter vesicles along actin filaments, coordinated by a positive auxin-actin feedback loop. Both polar auxin transport and vesicle cycling are inhibited by synthetic auxin transport inhibitors, such as 1-N-naphthylphthalamic acid (NPA), counteracting the effect of auxin; however, underlying targets and mechanisms are unclear. Using NMR, we map the NPA binding surface on the Arabidopsis thaliana ABCB chaperone TWISTED DWARF1 (TWD1). We identify ACTIN7 as a relevant, although likely indirect, TWD1 interactor, and show TWD1-dependent regulation of actin filament organization and dynamics and that TWD1 is required for NPA-mediated actin cytoskeleton remodeling. The TWD1-ACTIN7 axis controls plasma membrane presence of efflux transporters, and as a consequence act7 and twd1 share developmental and physiological phenotypes indicative of defects in auxin transport. These can be phenocopied by NPA treatment or by chemical actin (de)stabilization. We provide evidence that TWD1 determines downstream locations of auxin efflux transporters by adjusting actin filament debundling and dynamizing processes and mediating NPA action on the latter. This function appears to be evolutionary conserved since TWD1 expression in budding yeast alters actin polarization and cell polarity and provides NPA sensitivity.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Ligação a Tacrolimo/metabolismo , Citoesqueleto de Actina/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Transporte Biológico/genética , Transporte Biológico/fisiologia , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Proteínas de Ligação a Tacrolimo/genéticaRESUMO
Bladder pain syndrome (BPS) is poorly understood; however, there is a female predominance and comorbidity with irritable bowel syndrome (IBS). Here we test the hypothesis that linaclotide, a guanylate cyclase-C (GC-C) agonist approved for the treatment of IBS with constipation (IBS-C), may represent a novel therapeutic for BPS acting through a mechanism involving an inhibition of visceral organ cross-sensitization. We showed previously that infusion of dilute protamine sulfate (PS) into the bladder increased sensitivity and permeability in the bladder and colon. PS was infused into the bladder of female rats; sensitivity was assessed via application of von Frey filaments applied to the suprapubic area and the frequency of withdrawal responses was recorded. Colonic sensitivity was measured via visceromotor behavioral response to graded pressures of colorectal distension (CRD). Permeability was measured in vitro via transepithelial electrical resistance (TEER) and conductance (G). Linaclotide (3 µg/kg, p.o.) or vehicle was administered daily for 7 days prior to experiments. Rats treated with PS bladder infusion exhibited visceral hyperalgesia, as shown by a significantly higher response frequency to individual von Frey filaments and increased behavioral responses to CRD. Linaclotide attenuated bladder and colonic hyperalgesia to control levels. PS infusion into the bladder increased bladder and colon permeability measured as a decrease in TEER and increased G. Linaclotide significantly inhibited PS-induced colonic hyperpermeability while having no effect on bladder hyperpermeability. Our findings suggest a novel treatment paradigm for GC-C agonism in IBS-C and BPS mediated through a mechanism involving visceral organ crosstalk.
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Colo/efeitos dos fármacos , Colo/metabolismo , Guanilato Ciclase/metabolismo , Peptídeos/farmacologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/metabolismo , Animais , Ativação Enzimática/efeitos dos fármacos , Feminino , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacosRESUMO
Roots, leaves, and intermediate sections between roots and leaves (ISRL) of wheat seedlings show different physiological functions at the protein level. We performed the first integrative proteomic analysis of different tissues of the drought-tolerant wheat cultivar Hanxuan 10 (HX-10) and drought-sensitive cultivar Chinese Spring (CS) during a simulated drought and recovery. Differentially expressed proteins (DEPs) in the roots (122), ISRLs (146), and leaves (163) showed significant changes in expression in response to drought stress and recovery. Numerous DEPs associated with cell defense and detoxifications were significantly regulated in roots and ISRLs, while in leaves, DEPs related to photosynthesis showed significant changes in expression. A significantly larger number of DEPs related to stress defense were upregulated in HX-10 than in CS. Expression of six HSPs potentially related to drought tolerance was significantly upregulated under drought conditions, and these proteins were involved in a complex protein-protein interaction network. Further phosphorylation analysis showed that the phosphorylation levels of HSP60, HSP90, and HOP were upregulated in HX-10 under drought stress. We present an overview of metabolic pathways in wheat seedlings based on abscisic acid signaling and important protein expression patterns.
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Aclimatação , Proteínas de Plantas/metabolismo , Mapas de Interação de Proteínas , Plântula/fisiologia , Triticum/fisiologia , Secas , Fosforilação , Folhas de Planta/fisiologia , Raízes de Plantas/fisiologia , Proteoma/análise , Proteoma/metabolismo , ProteômicaRESUMO
MRP4 mediates the efflux of cGMP and cAMP and acts as an important regulator of these secondary messengers, thereby affecting signaling events mediated by cGMP and cAMP. Immunofluorescence staining showed high MRP4 expression localized predominantly in the apical membrane of rat colonic epithelium. In vitro studies were performed using a rat colonic mucosal layer mounted in an Ussing chamber. Linaclotide activation of the guanylate cyclase-C (GC-C)/cGMP pathway induced a concentration-dependent increase in transepithelial ion current [short-circuit current (Isc)] across rat colonic mucosa (EC50: 9.2 nM). Pretreatment of colonic mucosa with the specific MRP4 inhibitor MK571 potentiated linaclotide-induced electrolyte secretion and augmented linaclotide-stimulated intracellular cGMP accumulation. Notably, pretreatment with the phosphodiesterase 5 inhibitor sildenafil increased basal Isc, but had no amplifying effect on linaclotide-induced Isc. MRP4 inhibition selectively affected the activation phase, but not the deactivation phase, of linaclotide. In contrast, incubation with a GC-C/Fc chimera binding to linaclotide abrogated linaclotide-induced Isc, returning to baseline. Furthermore, linaclotide activation of GC-C induced cGMP secretion from the apical and basolateral membranes of colonic epithelium. MRP4 inhibition blocked cGMP efflux from the apical membrane, but not the basolateral membrane. These data reveal a novel, previously unrecognized mechanism that functionally couples GC-C-induced luminal electrolyte transport and cGMP secretion to spatially restricted, compartmentalized regulation by MRP4 at the apical membrane of intestinal epithelium. These findings have important implications for gastrointestinal disorders with symptoms associated with dysregulated fluid homeostasis, such as irritable bowel syndrome with constipation, chronic idiopathic constipation, and secretory diarrhea.
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GMP Cíclico/metabolismo , Eletrólitos/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Peptídeos/farmacologia , Propionatos/farmacologia , Quinolinas/farmacologia , Receptores Acoplados a Guanilato Ciclase/metabolismo , Receptores de Peptídeos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Transporte Biológico/efeitos dos fármacos , Colo/citologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/fisiologia , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Feminino , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/fisiologia , Cinética , Ratos , Ratos Sprague-Dawley , Receptores de EnterotoxinaRESUMO
Irritable bowel syndrome (IBS) is characterized by altered bowel habits, persistent pain and discomfort, and typically colorectal hypersensitivity. Linaclotide, a peripherally restricted 14 aa peptide approved for the treatment of IBS with constipation, relieves constipation and reduces IBS-associated pain in these patients presumably by activation of guanylate cyclase-C (GC-C), which stimulates production and release of cyclic guanosine monophosphate (cGMP) from intestinal epithelial cells. We investigated whether activation of GC-C by the endogenous agonist uroguanylin or the primary downstream effector of that activation, cGMP, directly modulates responses and sensitization of mechanosensitive colorectal primary afferents. The distal 2 cm of mouse colorectum with attached pelvic nerve was harvested and pinned flat mucosal side up for in vitro single-fiber recordings, and the encoding properties of mechanosensitive afferents (serosal, mucosal, muscular, and muscular-mucosal; M/M) to probing and circumferential stretch studied. Both cGMP (10-300 µM) and uroguanylin (1-1000 nM) applied directly to colorectal receptive endings significantly reduced responses of muscular and M/M afferents to stretch; serosal and mucosal afferents were not affected. Sensitized responses (i.e., increased responses to stretch) of muscular and M/M afferents were reversed by cGMP, returning responses to stretch to control. Blocking the transport of cGMP from colorectal epithelia by probenecid, a mechanism validated by studies in cultured intestinal T84 cells, abolished the inhibitory effect of uroguanylin on M/M afferents. These results suggest that GC-C agonists like linaclotide alleviate colorectal pain and hypersensitivity by dampening stretch-sensitive afferent mechanosensitivity and normalizing afferent sensitization.
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Colo/enzimologia , Guanilato Ciclase/metabolismo , Mecanorreceptores/enzimologia , Reto/enzimologia , Vias Aferentes/enzimologia , Animais , Linhagem Celular Tumoral , Colo/inervação , Ativação Enzimática/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reto/inervaçãoRESUMO
Here, we conducted the first large-scale leaf phosphoproteome analysis of two bread wheat cultivars by liquid chromatography-tandem mass spectrometry. Altogether, 1802 unambiguous phosphorylation sites representing 1175 phosphoproteins implicated in various molecular functions and cellular processes were identified by gene ontology enrichment analysis. Among the 1175 phosphoproteins, 141 contained 3-10 phosphorylation sites. The phosphorylation sites were located more frequently in the N- and C-terminal regions than in internal regions, and â¼70% were located outside the conserved regions. Conservation analysis showed that 90.5% of the phosphoproteins had phosphorylated orthologs in other plant species. Eighteen significantly enriched phosphorylation motifs, of which six were new wheat phosphorylation motifs, were identified. In particular, 52 phosphorylated transcription factors (TFs), 85 protein kinases (PKs), and 16 protein phosphatases (PPs) were classified and analyzed in depth. All the Tyr phosphorylation sites were in PKs such as mitogen-activated PKs (MAPKs) and SHAGGY-like kinases. A complicated cross-talk phosphorylation regulatory network based on PKs such as Snf1-related kinases (SnRKs), calcium-dependent PKs (CDPKs), and glycogen synthase kinase 3 (GSK3) and PPs including PP2C, PP2A, and BRI1 suppressor 1 (BSU1)-like protein (BSL) was constructed and was found to be potentially involved in rapid leaf growth. Our results provide a series of phosphoproteins and phosphorylation sites in addition to a potential network of phosphorylation signaling cascades in wheat seedling leaves.
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Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Proteômica/métodos , Plântula/metabolismo , Transdução de Sinais , Triticum/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Cromatografia Líquida , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Fosfoproteínas/química , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilação , Proteínas de Plantas/química , Proteínas de Plantas/genética , Estrutura Terciária de Proteína , Proteoma/química , Proteoma/genética , Proteoma/metabolismo , Homologia de Sequência de Aminoácidos , Espectrometria de Massas em TandemRESUMO
BACKGROUND & AIMS: Linaclotide is a minimally absorbed agonist of guanylate cyclase-C (GUCY2C or GC-C) that reduces symptoms associated with irritable bowel syndrome with constipation (IBS-C). Little is known about the mechanism by which linaclotide reduces abdominal pain in patients with IBS-C. METHODS: We determined the effects of linaclotide on colonic sensory afferents in healthy mice and those with chronic visceral hypersensitivity. We assessed pain transmission by measuring activation of dorsal horn neurons in the spinal cord in response to noxious colorectal distention. Levels of Gucy2c messenger RNA were measured in tissues from mice using quantitative reverse transcription polymerase chain reaction and in situ hybridization. We used human intestinal cell lines to measure release of cyclic guanosine-3',5'-monophosphate (cGMP) by linaclotide. We performed a post-hoc analysis of data from a phase III, double-blind, parallel-group study in which 805 patients with IBS-C were randomly assigned to groups given an oral placebo or 290 µg linaclotide once daily for 26 weeks. We quantified changes in IBS-C symptoms, including abdominal pain. RESULTS: In mice, linaclotide inhibited colonic nociceptors with greater efficacy during chronic visceral hypersensitivity. Intra-colonic administration of linaclotide reduced signaling of noxious colorectal distention to the spinal cord. The colonic mucosa, but not neurons, was found to express linaclotide's target, GC-C. The downstream effector of GC-C, cGMP, was released after administration of linaclotide and also inhibited nociceptors. The effects of linaclotide were lost in Gucy2c(-/-) mice and prevented by inhibiting cGMP transporters or removing the mucosa. During 26 weeks of linaclotide administration, a significantly greater percentage of patients (70%) had at least a 30% reduction in abdominal pain compared with patients given placebo (50%). CONCLUSIONS: We have identified an analgesic mechanism of linaclotide: it activates GC-C expressed on mucosal epithelial cells, resulting in the production and release of cGMP. This extracellular cGMP acts on and inhibits nociceptors, thereby reducing nociception. We also found that linaclotide reduces chronic abdominal pain in patients with IBS-C.
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Dor Abdominal/prevenção & controle , Colo/inervação , GMP Cíclico/fisiologia , Guanilato Ciclase/fisiologia , Nociceptores/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Dor Abdominal/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Células CACO-2 , Linhagem Celular , Colo/efeitos dos fármacos , Colo/patologia , Modelos Animais de Doenças , Método Duplo-Cego , Feminino , Humanos , Síndrome do Intestino Irritável/induzido quimicamente , Síndrome do Intestino Irritável/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Peptídeos Natriuréticos/farmacologia , Nociceptores/fisiologia , Receptores do Fator Natriurético Atrial/fisiologia , Receptores de Enterotoxina , Receptores Acoplados a Guanilato Ciclase/fisiologia , Receptores de Peptídeos/fisiologia , Resultado do Tratamento , Ácido Trinitrobenzenossulfônico/efeitos adversosRESUMO
As an abundant ROS, hydrogen peroxide (H2 O2 ) plays pivotal roles in plant growth and development. In this work, we conducted for the first time an iTRAQ-based quantitative proteomic analysis of wheat seedling growth under different exogenous H2 O2 treatments. The growth of seedlings and roots was significantly restrained by increased H2 O2 concentration stress. Malondialdehyde, soluble sugar, and proline contents as well as peroxidase activity increased with increasing H2 O2 levels. A total of 3,425 proteins were identified by iTRAQ, of which 157 showed differential expression and 44 were newly identified H2 O2 -responsive proteins. H2 O2 -responsive proteins were mainly involved in stress/defense/detoxification, signal transduction, and carbohydrate metabolism. It is clear that up-regulated expression of signal transduction and stress/defence/detoxification-related proteins under H2 O2 stress, such as plasma membrane intrinsic protein 1, fasciclin-like arabinogalactan protein, and superoxide dismutase, could contribute to H2 O2 tolerance of wheat seedlings. Increased gluconeogenesis (phosphoenol-pyruvate carboxykinase) and decreased pyruvate kinase proteins are potentially related to the higher H2 O2 tolerance of wheat seedlings. A metabolic pathway of wheat seedling growth under H2 O2 stress is presented.
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Peróxido de Hidrogênio/toxicidade , Marcação por Isótopo/métodos , Redes e Vias Metabólicas/efeitos dos fármacos , Proteômica/métodos , Plântula/crescimento & desenvolvimento , Estresse Fisiológico/efeitos dos fármacos , Triticum/metabolismo , Análise por Conglomerados , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Proteínas de Plantas/classificação , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Proteoma/metabolismo , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/metabolismo , Estresse Fisiológico/genética , Transcrição Gênica/efeitos dos fármacos , Triticum/efeitos dos fármacos , Triticum/genética , Triticum/crescimento & desenvolvimentoRESUMO
In order to overcome the discreteness of input data and training data in deep neural network (DNN), the multivariable response surface function was used to revise input data and training data in this paper. The loss function based on the data on the response surface was derived, DNN based on multivariable response surface function (MRSF-DNN) was established. MRSF-DNN model of recycled brick aggregate concrete compressive strength was established, in which coarse aggregate volume content, fine aggregate volume content and water cement ratio are influencing factors. Furthermore, the predictive analysis and extended analysis of MRSF-DNN model were carried out. The results show that: MRSF-DNN model had high prediction accuracy, the correlation coefficient between the real values and the forecast values was 0.9882, the relative error was between -0.5% and 1%. Furthermore, MRSF-DNN had more stable prediction ability and stronger generalization ability than DNN.
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Cimentos Ósseos , Generalização Psicológica , Força Compressiva , Cimentos de Ionômeros de Vidro , Redes Neurais de ComputaçãoRESUMO
In recent intelligent-robot-assisted surgery studies, an urgent issue is how to detect the motion of instruments and soft tissue accurately from intra-operative images. Although optical flow technology from computer vision is a powerful solution to the motion-tracking problem, it has difficulty obtaining the pixel-wise optical flow ground truth of real surgery videos for supervised learning. Thus, unsupervised learning methods are critical. However, current unsupervised methods face the challenge of heavy occlusion in the surgical scene. This paper proposes a novel unsupervised learning framework to estimate the motion from surgical images under occlusion. The framework consists of a Motion Decoupling Network to estimate the tissue and the instrument motion with different constraints. Notably, the network integrates a segmentation subnet that estimates the segmentation map of instruments in an unsupervised manner to obtain the occlusion region and improve the dual motion estimation. Additionally, a hybrid self-supervised strategy with occlusion completion is introduced to recover realistic vision clues. Extensive experiments on two surgical datasets show that the proposed method achieves accurate motion estimation for intra-operative scenes and outperforms other unsupervised methods, with a margin of 15% in accuracy. The average estimation error for tissue is less than 2.2 pixels on average for both surgical datasets.
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Procedimentos Cirúrgicos Robóticos , Cirurgia Assistida por Computador , Algoritmos , Movimento (Física) , Cirurgia Assistida por Computador/métodosRESUMO
BACKGROUND: The analyses of protein synthesis, accumulation and regulation during grain development in wheat are more complex because of its larger genome size compared to model plants such as Arabidopsis and rice. In this study, grains from two wheat cultivars Jimai 20 and Zhoumai 16 with different gluten quality properties were harvested at five development stages, and were used to displayed variable expression patterns of grain proteins. RESULTS: Proteome characterization during grain development in Chinese bread wheat cultivars Jimai 20 and Zhoumai 16 with different quality properties was investigated by 2-DE and tandem MALDI-TOF/TOF-MS. Identification of 117 differentially accumulated protein spots representing 82 unique proteins and five main expression patterns enabled a chronological description of wheat grain formation. Significant proteome expression differences between the two cultivars were found; these included 14 protein spots that accumulated in both cultivars but with different patterns and 27 cultivar-different spots. Among the cultivar-different protein spots, 14 accumulated in higher abundance in Jimai 20 than in Zhoumai 16, and included NAD-dependent isocitrate dehydrogenase, triticin precursor, LMW-s glutenin subunit and replication factor C-like protein. These proteins are likely to be associated with superior gluten quality. In addition, some proteins such as class II chitinase and peroxidase 1 with isoforms in developing grains were shown to be phosphorylated by Pro-Q Diamond staining and phosphorprotein site prediction. Phosphorylation could have important roles in wheat grain development. qRT-PCR analysis demonstrated that transcriptional and translational expression patterns of many genes were significantly different. CONCLUSIONS: Wheat grain proteins displayed variable expression patterns at different developmental stages and a considerable number of protein spots showed differential accumulation between two cultivars. Differences in seed storage proteins were considered to be related to different quality performance of the flour from these wheat cultivars. Some proteins with isoforms were phosphorylated, and this may reflect their importance in grain development. Our results provide new insights into proteome characterization during grain development in different wheat genotypes.
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Regulação da Expressão Gênica de Plantas , Glutens/metabolismo , Proteoma/análise , Sementes/crescimento & desenvolvimento , Triticum/metabolismo , Sequência de Aminoácidos , Eletroforese em Gel Bidimensional , Glutens/genética , Dados de Sequência Molecular , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteômica , Sementes/genética , Sementes/metabolismo , Especificidade da Espécie , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Transcrição Gênica , Triticum/genética , Triticum/crescimento & desenvolvimento , LeguminasRESUMO
Gliadins were the major components of wheat storage proteins and determine the extensibility properties of gluten dough. In this work, 19 new full-length γ-gliadin genes were isolated from various Aegilops and Triticum species. Sequence characterization showed that a specific octapeptide and celiac disease (CD)-toxic epitope Gliγ-3 (VQGQGIIQPQQPAQL) were present in the rich glutamine domain and C-terminal non-repetitive domain, respectively. Based on the sequence features of both peptides, a new classification system for γ-gliadin gene family was established, in which γ-gliadins were classified into two types (types I and II) with each consisting of two groups. An uneven distribution of different types and groups of γ-gliadin genes was exhibited among 11 Aegilops and Triticum genomes. Phylogenetic analysis revealed that types I and II genes diverged at about 14 MYA while the divergence of 4 γ-gliadin group genes occurred at around 10 MYA almost simultaneously. The γ-gliadin genes from S(l) and B genomes displayed a different transcriptional expression pattern during grain development, and rapid increasing of gliadin mRNA and proteins occurred at 15-20 DPA. In addition, genome-specific variations of CD-toxic epitopes among Aegilops and Triticum genomes were found. The A genome and its related progenitor genomes A(u) and A(m) had fewer CD epitopes than other genomes, suggesting that these genomes might be valuable gene resources to remove CD toxic peptides for wheat quality improvement.
Assuntos
Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Gliadina/genética , Poaceae/genética , Triticum/genética , Sequência de Aminoácidos , Doença Celíaca/imunologia , Epitopos/imunologia , Evolução Molecular , Perfilação da Expressão Gênica , Gliadina/química , Gliadina/imunologia , Gliadina/metabolismo , Dados de Sequência Molecular , Peptídeos/química , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Padrões de Referência , Sementes/genética , Sementes/crescimento & desenvolvimento , Alinhamento de Sequência , Transcrição GênicaRESUMO
The α-gliadins are associated with human celiac disease. A total of 23 noninterrupted full open reading frame α-gliadin genes and 19 pseudogenes were cloned and sequenced from C, M, N, and U genomes of four diploid Aegilops species. Sequence comparison of α-gliadin genes from Aegilops and Triticum species demonstrated an existence of extensive allelic variations in Gli-2 loci of the four Aegilops genomes. Specific structural features were found including the compositions and variations of two polyglutamine domains (QI and QII) and four T cell stimulatory toxic epitopes. The mean numbers of glutamine residues in the QI domain in C and N genomes and the QII domain in C, N, and U genomes were much higher than those in Triticum genomes, and the QI domain in C and N genomes and the QII domain in C, M, N, and U genomes displayed greater length variations. Interestingly, the types and numbers of four T cell stimulatory toxic epitopes in α-gliadins from the four Aegilops genomes were significantly less than those from Triticum A, B, D, and their progenitor genomes. Relationships between the structural variations of the two polyglutamine domains and the distributions of four T cell stimulatory toxic epitopes were found, resulting in the α-gliadin genes from the Aegilops and Triticum genomes to be classified into three groups.
Assuntos
Doença Celíaca/genética , Doença Celíaca/imunologia , Epitopos/genética , Variação Genética , Genoma de Planta , Gliadina/genética , Poaceae/genética , Alelos , Doença Celíaca/classificação , DNA de Plantas/química , DNA de Plantas/metabolismo , Diploide , Variação Genética/imunologia , Poaceae/classificação , Especificidade da Espécie , Triticum/genética , Triticum/metabolismoRESUMO
Recently, airflow sensors have attracted great attention due to their unique characteristics. However, the preparation of high-performance airflow sensors via extraordinarily simple, controllable and cost-effective methods remains a great challenge. Herein, inspired by the fluff system of the spider, an ultrasensitive fluffy-like airflow sensor with carbon fibers (CFs) uniformly and firmly planted on the surface of a polyvinyl alcohol (PVA) fibrous substrate has been easily fabricated using electrostatic flocking technology. The fluffy-like structure endows the airflow sensor with superior properties including ultra-sensitivity, fast response time (0.103 s), low airflow velocity detection limit (0.068 m s-1), ultra-sensitive detection in a wide airflow range (0.068-16 m s-1), and multi-directional consistent response to airflow. This sensor can be used to accurately recognize sound waves and voiceless speech and detect human and object motions in different postures and speeds. This work presents insights into designing and preparing high-performance airflow sensors on a large-scale for sound recognition, motion monitoring, and assisting the disabled.