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1.
Mol Biol Evol ; 41(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38376543

RESUMO

In mammalian research, it has been debated what can initiate an evolutionary tradeoff between different senses, and the phenomenon of sensory tradeoff in rodents, the most abundant mammalian clade, is not evident. The Nile rat (Arvicanthis niloticus), a murid rodent, recently adapted to a diurnal niche through an evolutionary acquisition of daylight vision with enhanced visual acuity. As such, this model provides an opportunity for a cross-species investigation where comparative morphological and multi-omic analyses of the Nile rat are made with its closely related nocturnal species, e.g. the mouse (Mus musculus) and the rat (Rattus norvegicus). Thus, morphological examinations were performed, and evolutionary reductions in relative sizes of turbinal bone surfaces, the cribriform plate, and the olfactory bulb were discovered in Nile rats. Subsequently, we compared multiple murid genomes, and profiled olfactory epithelium transcriptomes of mice and Nile rats at various ages with RNA sequencing. The results further demonstrate that, in comparison with mouse olfactory receptor (OR) genes, Nile rat OR genes have experienced less frequent gain, more frequent loss, and more frequent expression reduction during their evolution. Furthermore, functional degeneration of coding sequences in the Nile rat lineage was found in OR genes, yet not in other genes. Taken together, these results suggest that acquisition of improved vision in the Nile rat has been accompanied by degeneration of both olfaction-related anatomical structures and OR gene repertoires, consistent with the hypothesis of an olfaction-vision tradeoff initiated by the switch from a nocturnal to a diurnal lifestyle in mammals.


Assuntos
Ritmo Circadiano , Murinae , Animais , Ritmo Circadiano/fisiologia , Mamíferos , Genoma
2.
J Am Chem Soc ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838245

RESUMO

The activity of Ru-based alkaline hydrogen oxidation reaction (HOR) electrocatalysts usually decreases rapidly at potentials higher than 0.1 V (vs a reversible hydrogen electrode (RHE)), which significantly limits the lifetime of fuel cells. It is found that this phenomenon is caused by the overadsorption of the O species due to the overcharging of Ru nanoparticles at high potentials. Here, Mn1Ox(OH)y clusters-modified Ru nanoparticles (Mn1Ox(OH)y@Ru/C) were prepared to promote charge transfer from overcharged Ru nanoparticles to Mn1Ox(OH)y clusters. Mn1Ox(OH)y@Ru/C exhibits high HOR activity and stability over a wide potential range of 0-1.0 V. Moreover, a hydroxide exchange membrane fuel cell with a Mn1Ox(OH)y@Ru/C anode delivers a high peak power density of 1.731 W cm-2, much superior to that of a Pt/C anode. In situ X-ray absorption fine structure (XAFS) analysis and density functional theory (DFT) calculations reveal that Mn in Mn1Ox(OH)y clusters could receive more electrons from overcharged Ru at higher potentials and significantly decrease the overadsorption of the O species on Ru, thus permitting the HOR on Ru to proceed at high potentials. This study provides guidance for the design of alkaline HOR catalysts without activity decay at high potentials.

3.
Small ; : e2401404, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644200

RESUMO

Developing low-loading platinum-group-metal (PGM) catalysts is one of the key challenges in commercializing anion-exchange-membrane-fuel-cells (AEMFCs), especially for hydrogen oxidation reaction (HOR). Here, ruthenium-iridium nanoparticles being deposited on a Zn-N species-doped carbon carrier (Ru6Ir/Zn-N-C) are synthesized and used as an anodic catalyst for AEMFCs. Ru6Ir/Zn-N-C shows extremely high mass activity (5.87 A mgPGM -1) and exchange current density (0.92 mA cm-2), which is 15.1 and 3.9 times that of commercial Pt/C, respectively. Based on the Ru6Ir/Zn-N-C AEMFCs achieve a peak power density of 1.50 W cm-2, surpassing the state-of-the-art commercial PtRu catalysts and the power ratio of the normalized loading is 14.01 W mgPGM anode -1 or 5.89 W mgPGM -1 after decreasing the anode loading (87.49 µg cm-2) or the total PGM loading (0.111 mg cm-2), satisfying the US Department of Energy's PGM loading target. Moreover, the solvent and solute isotope separation method is used for the first time to reveal the kinetic process of HOR, which shows the reaction is influenced by the adsorption of H2O and OH-. The improvement of the hydrogen bond network connectivity of the electric double layer by adjusting the interfacial H2O structure together with the optimized HBE and OHBE is proposed to be responsible for the high HOR activity of Ru6Ir/Zn-N-C.

4.
BMC Biol ; 21(1): 57, 2023 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-36941675

RESUMO

BACKGROUND: Individual organisms may exhibit phenotypic plasticity when they acclimate to different conditions. Such plastic responses may facilitate or constrain the adaptation of their descendant populations to new environments, complicating their evolutionary trajectories beyond the genetic blueprint. Intriguingly, phenotypic plasticity itself can evolve in terms of its direction and magnitude during adaptation. However, we know little about what determines the evolution of phenotypic plasticity, including gene expression plasticity. Recent laboratory-based studies suggest dominance of reversing gene expression plasticity-plastic responses that move the levels of gene expression away from the new optima. Nevertheless, evidence from natural populations is still limited. RESULTS: Here, we studied gene expression plasticity and its evolution in the montane and lowland populations of an elevationally widespread songbird-the Rufous-capped Babbler (Cyanoderma ruficeps)-with reciprocal transplant experiments and transcriptomic analyses; we set common gardens at altitudes close to these populations' native ranges. We confirmed the prevalence of reversing plasticity in genes associated with altitudinal adaptation. Interestingly, we found a positive relationship between magnitude and degree of evolution in gene expression plasticity, which was pertinent to not only adaptation-associated genes but also the whole transcriptomes from multiple tissues. Furthermore, we revealed that genes with weaker expressional interactions with other genes tended to exhibit stronger plasticity and higher degree of plasticity evolution, which explains the positive magnitude-evolution relationship. CONCLUSIONS: Our experimental evidence demonstrates that species may initiate their adaptation to new habitats with genes exhibiting strong expression plasticity. We also highlight the role of expression interdependence among genes in regulating the magnitude and evolution of expression plasticity. This study illuminates how the evolution of phenotypic plasticity in gene expression facilitates the adaptation of species to challenging environments in nature.


Assuntos
Aclimatação , Adaptação Fisiológica , Fenótipo , Adaptação Fisiológica/genética , Altitude , Expressão Gênica , Evolução Biológica
5.
J Am Chem Soc ; 145(50): 27867-27876, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38079607

RESUMO

Efficient and CO-tolerant catalysts for alkaline hydrogen oxidation (HOR) are vital to the commercial application of anion exchange membrane fuel cells (AEMFCs). Herein, a robust Ru-based catalyst (Ru/VOC) with ultrasmall Ru nanoparticles supported on carbon frameworks with atomically dispersed V-O species is prepared elaborately. The catalyst exhibits a remarkable mass activity of 3.44 mA µgPGM, which is 31.3 times that of Ru/C and even 4.7 times higher than that of Pt/C. Moreover, the Ru/VOC anode can achieve a peak power density (PPD) of 1.194 W cm-2, much superior to that of Ru/C anode and even better than that of Pt/C anode. In addition, the catalyst also exhibits superior stability and exceptional CO tolerance. Experimental results and density functional theory (DFT) calculations demonstrate that V-O species are ideal OH- adsorption sites, which allow Ru to release more sites for hydrogen adsorption. Furthermore, the electron transfer from Ru nanoparticles to the carbon substrate regulates the electronic structure of Ru, reducing the hydrogen binding energy (HBE) and the CO adsorption energy on Ru, thus boosting the alkaline HOR performance and CO tolerance of the catalyst. This is the first report that oxophilic single atoms distributed on carbon frameworks serve as OH- adsorption sites for efficient hydrogen oxidation, opening up new guidance for the elaborate design of high-activity catalysts for the alkaline HOR.

6.
Biotechnol Lett ; 43(6): 1163-1174, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33677804

RESUMO

OBJECTIVES: Growing evidence shows that long non-coding RNAs (lncRNAs) are widely involved in the progression of multiple diseases, including ischemic stroke. The aim of this study was to explore the function and underlying mechanism of lncRNAs small nucleolar RNA host gene 1 (SNHG1) in ischemic stroke. RESULTS: SNHG1 and salt-induced kinase 1 (SIK1) were upregulated in oxygen-glucose deprivation/reperfusion (OGD/R)-induced bEnd3 cells. SNHG1 downregulation promoted OGD/R-induced injury through decreasing cell proliferation and increasing apoptosis, which was reversed by upregulating SIK1 or downregulating miR-298. Moreover, SIK1 interference had similar functions with SNHG1 knockdown in OGD/R-treated bEnd3 cells. In addition, miR-298 was a direct target of SNHG1 and could specifically bind to SIK1. Furthermore, SNHG1 functioned as a molecular sponge of miR-298 to regulate SIK1 expression. CONCLUSION: SNHG1 knockdown enhanced OGD/R-induced injury in bEnd3 cells by regulating miR-298/SIK1 axis, which might provide promising therapeutic target for treatment of ischemic stroke.


Assuntos
Encéfalo/citologia , AVC Isquêmico/genética , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genética , RNA Longo não Codificante/genética , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , AVC Isquêmico/induzido quimicamente , Camundongos , Modelos Biológicos , Regulação para Cima
7.
Neurol Sci ; 41(5): 1193-1199, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31901124

RESUMO

INTRODUCTION: To improve the accuracy of ultrasound techniques for the assessment of carotid stenosis, we designed a novel carotid artery stenosis ultrasound scale (CASUS), and evaluated its accuracy, reliability, and its value in predicting the occurrence of cardiovascular and cerebrovascular diseases in a prospective study. METHODS: A total of 750 patients with first-time ischemic stroke and hospitalized within 24 h were enrolled in the study. Using color Doppler ultrasound (CDUS), the degree of stenosis and blood flow (BF) in bilateral internal carotid arteries (ICA) and the V1-V3 segment of vertebral arteries (VA) was assessed. Cubic simulation curves for BF and global blood flow (GBF) over the stenosis score (SS), total stenosis score (TSS), and radiological imaging- total stenosis score (RI-TSS) were fitted and compared. The receiver operating characteristic (ROC) curves using TSS, RI-TSS, or GBF to predict various ischemic stroke endpoints were also analyzed and compared. RESULTS: There was a linear relationship between SS and BF both ICA and VA (R2 were 0.734 and 0.783, respectively, both P < 0.05). Both TSS and RI-TSS with GBF showed an inverse "S" curve relationship (R2 was 0.839 and 0.843, all P < 0.05). The AUC values of TSS-based and RI-TSS-based predictions of each endpoint were all greater than 0.7 (all P < 0.05), but the differences of the AUC values between TSS, RI-TSS, and GBF were not statistically significant (all P > 0.05). CONCLUSIONS: The novel CASUS can better reflect the level of cerebral reperfusion in patients with ischemic stroke and can better predict the occurrence of cardiovascular and cerebrovascular diseases.


Assuntos
Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , AVC Isquêmico/diagnóstico por imagem , Ultrassonografia Doppler , Artéria Vertebral/diagnóstico por imagem , Idoso , Artéria Carótida Interna/patologia , Feminino , Humanos , AVC Isquêmico/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Artéria Vertebral/patologia
8.
Stroke ; 49(7): 1610-1617, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29895539

RESUMO

BACKGROUND AND PURPOSE: Blood pressure (BP) control in the early phase of stroke is controversial to reduce the risk of poststroke cognitive impairment (PSCI). This study was to investigate the impact of BP levels in the early phase of ischemic stroke and stroke subtype on PSCI. METHODS: Seven hundred and ninety-six patients with acute ischemic stroke were included. Cognitive function was assessed after stroke onset using the Montreal Cognitive Assessment. Patients were divided into quintiles according to systolic BP and diastolic BP levels in the early phase. Subtype analyses were according to Trial of ORG 10172 in Acute Stroke Treatment classification (infarct cause) and Oxfordshire Community Stroke Project classification (infarct location). RESULTS: After adjusting for multiple variables, the quintiles with the lowest systolic BP (Q1, 102-127 mm Hg) and with the highest systolic BP (Q5, 171-215 mm Hg) were associated with increased PSCI risk (odds ratio, 1.83; 95% confidence interval, 1.64-2.28; P=0.007 in Q1; odds ratio, 2.32; 95% confidence interval, 1.74-2.90; P<0.001 in Q5) at 3 months as compared with the middle quintile (Q3, 143-158 mm Hg). Similar association was found in diastolic BP quintiles. The analysis of cerebral infarction subtype demonstrated that both large artery atherosclerosis and total anterior circulation infarct were associated with increased risk of PSCI at 3 months after adjusting for multiple variables (large artery atherosclerosis: odds ratio, 1.42; 95% confidence interval, 1.06-1.90; P=0.031; total anterior circulation infarct: odds ratio, 1.68; 95% confidence interval, 1.32-2.15; P=0.001). CONCLUSIONS: Lower or higher BP in the early phase of ischemic stroke was correlated with increased PSCI risk at 3 months. Maintaining systolic/diastolic BP in the levels of 143 to 158/93 to 102 mm Hg might be beneficial to reduce the occurrence of PSCI. Moreover, large artery atherosclerosis subtype and total anterior circulation infarct subtype were correlated with increased PSCI risk at 3 months. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org. Unique identifier: ChiCTR-TRC-14004804.


Assuntos
Pressão Sanguínea/fisiologia , Isquemia Encefálica/complicações , Disfunção Cognitiva/etiologia , Acidente Vascular Cerebral/complicações , Idoso , Determinação da Pressão Arterial , Isquemia Encefálica/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Risco , Acidente Vascular Cerebral/fisiopatologia
9.
Bioinformatics ; 33(21): 3505-3507, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28666356

RESUMO

MOTIVATION: Genome-scale phenotypic data are available for many model organisms, yet existing tools to functionally interpret gene sets from these phenotypic data are largely based on mutagenesis-derived phenotypes observed in mouse or human. RESULTS: Data from both mutagenesis and knockdown experiments are incorporated into modPhEA to allow users to perform enrichment analyses based on phenotypes observed in budding yeast (Saccharomyces cerevisiae), roundworm (Caenorhabditis elegans), fruit fly (Drosophila melanogaster), zebrafish (Danio rerio), mouse (Mus musculus) and humans (Homo sapiens). The phenotypes analysed can be customized to investigate complex traits and gene sets from any fully sequenced animal or fungal genome are also supported by modPhEA. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://evol.nhri.org.tw/modPhEA/. CONTACT: liaoby@nhri.org.tw. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Fenótipo , Software , Animais , Caenorhabditis elegans/genética , Drosophila melanogaster/genética , Genes , Genoma , Humanos , Camundongos , Modelos Animais , Mutagênese , Saccharomyces cerevisiae/genética , Peixe-Zebra/genética
10.
Med Sci Monit ; 24: 6688-6694, 2018 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-30243025

RESUMO

BACKGROUND The optimal medical regimen for managing hypertension during acute phase of lacunar infarcts has not yet been clarified in real world setting. The aim of this study was to evaluate blood pressure lowering regimens on neurological progression and clinical outcomes during the acute phase of lacunar infarcts. MATERIAL AND METHODS For this study, 411 patients with first-episode lacunar infarcts and hypertension within 24 hours of symptom onset were included. All patients received antihypertension therapies, with different regimens, as well as routine medication during first 7 days after onset. There were 6 proposed antihypertensive treatments: calcium channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), ß-blocker (ß-B), and diuretic drug (DD) alone or in combination. Neurological progression was defined as worsening by ≥1 point in the National Institute of Health Stroke Scale (NIHSS) for motor function. The outcome was assessed using the modified Rankin Scale (mRS): favorable outcome (mRS of 0-1) or unfavorable outcome (mRS 2-5). RESULTS Logistic regression analysis showed that combination therapy with CCB, ACEI/ARB, and ß-B exhibited the lowest risk of deterioration (OR=0.48, P=0.019) and unfavorable outcomes (OR=0.50, P=0.022). Similarly, combination therapy with CCB, ACEI/ARB, and DD exhibited lower risk of deterioration (OR=0.63, P=0.033) and unfavorable outcome (OR=0.77, P=0.042) at 3 months. CONCLUSIONS Rational blood pressure lowering was beneficial to the functional outcomes of patients during acute phase of lacunar infarcts, and combination therapy was better than mono-drug therapy.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Acidente Vascular Cerebral Lacunar/tratamento farmacológico , Antagonistas Adrenérgicos beta/farmacologia , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/fisiologia , Bloqueadores dos Canais de Cálcio/farmacologia , China , Quimioterapia Combinada/métodos , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Proc Natl Acad Sci U S A ; 112(15): 4707-12, 2015 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-25825715

RESUMO

High-throughput gene expression profiling has revealed substantial leaky and extraneous transcription of eukaryotic genes, challenging the perceptions that transcription is strictly regulated and that changes in transcription have phenotypic consequences. To assess the functional implications of mRNA transcription directly, we analyzed mRNA expression data derived from microarrays, RNA-sequencing, and in situ hybridization, together with phenotype data of mouse mutants as a proxy of gene function at the tissue level. The results indicated that despite the presence of widespread ectopic transcription, mRNA expression and mutant phenotypes of mammalian genes or tissues remain associated. The expression-phenotype association at the gene level was particularly strong for tissue-specific genes, and the association could be underestimated due to data insufficiency and incomprehensive phenotyping of mouse mutants; the strength of expression-phenotype association at the tissue level depended on tissue functions. Mutations on genes expressed at higher levels or expressed at earlier embryonic stages more often result in abnormal phenotypes in the tissues where they are expressed. The mRNA expression profiles that have stronger associations with their phenotype profiles tend to be more evolutionarily conserved, indicating that the evolution of transcriptome and the evolution of phenome are coupled. Therefore, mutations resulting in phenotypic aberrations in expressed tissues are more likely to occur in highly transcribed genes, tissue-specific genes, genes expressed during early embryonic stages, or genes with evolutionarily conserved mRNA expression profiles.


Assuntos
Perfilação da Expressão Gênica , Genoma/genética , Mutação , RNA Mensageiro/genética , Algoritmos , Animais , Evolução Molecular , Ontologia Genética , Camundongos , Modelos Genéticos , Análise de Sequência com Séries de Oligonucleotídeos , Especificidade de Órgãos/genética , Fenótipo , RNA Mensageiro/metabolismo , Seleção Genética
12.
J Biol Chem ; 289(42): 29322-33, 2014 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-25164813

RESUMO

Inflammasomes are multi-protein complexes that regulate chronic inflammation-associated diseases by inducing interleukin-1 ß (IL-1ß) secretion. Numerous components involved in inflammasome activation have been identified, but the mechanisms of inflammasome-mediated IL-1ß secretion have not yet been fully explored. Here, we demonstrate that end-binding protein 1 (EB1), which is required for activation of AIM2 inflammasome complex, links the AIM2 inflammasome to autophagy-dependent secretion. Imaging studies revealed that AIM2 inflammasomes colocalize with microtubule organizing centers and autophagosomes. Biochemical analyses showed that poly(dA-dT)-activated AIM2 inflammasomes induce autophagy and IL-1ß secretion in an LC3-dependent fashion. Furthermore, depletion of EB1 decreases autophagic shedding and intracellular trafficking. Finally, we found that the 5'-AMP activated protein kinase may regulate this EB1-mediated autophagy-based inflammasome-induced secretion of IL-1ß. These findings reveal a novel EB1-mediated pathway for the secretion of IL-1ß.


Assuntos
Autofagia , Proteínas de Ligação a DNA/metabolismo , Inflamassomos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular , Células HeLa , Humanos , Inflamação , Interleucina-1beta/metabolismo , Microtúbulos/metabolismo
13.
Nucleic Acids Res ; 41(5): 2907-17, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23341037

RESUMO

Because regulation of its activity is instrumental either to support cell proliferation and growth or to promote cell death, the universal myo-inositol phosphate synthase (MIPS), responsible for myo-inositol biosynthesis, is a critical enzyme of primary metabolism. Surprisingly, we found this enzyme to be imported in the nucleus and to interact with the histone methyltransferases ATXR5 and ATXR6, raising the question of whether MIPS1 has a function in transcriptional regulation. Here, we demonstrate that MIPS1 binds directly to its promoter to stimulate its own expression by locally inhibiting the spreading of ATXR5/6-dependent heterochromatin marks coming from a transposable element. Furthermore, on activation of pathogen response, MIPS1 expression is reduced epigenetically, providing evidence for a complex regulatory mechanism acting at the transcriptional level. Thus, in plants, MIPS1 appears to have evolved as a protein that connects cellular metabolism, pathogen response and chromatin remodeling.


Assuntos
Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Meristema/genética , Mio-Inositol-1-Fosfato Sintase/fisiologia , Apoptose , Arabidopsis/citologia , Arabidopsis/enzimologia , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/fisiologia , Núcleo Celular/enzimologia , Montagem e Desmontagem da Cromatina , Citoplasma/enzimologia , Metilação de DNA , Epigênese Genética , Flagelina/imunologia , Expressão Gênica , Histonas/metabolismo , Meristema/citologia , Meristema/enzimologia , Metilação , Metiltransferases/metabolismo , Metiltransferases/fisiologia , Mio-Inositol-1-Fosfato Sintase/genética , Mio-Inositol-1-Fosfato Sintase/metabolismo , Imunidade Vegetal/genética , Regiões Promotoras Genéticas , Ligação Proteica , Processamento de Proteína Pós-Traducional , Transporte Proteico , Nicotiana
14.
Proc Natl Acad Sci U S A ; 107(16): 7353-8, 2010 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-20368429

RESUMO

The relative importance of protein function change and gene expression change in phenotypic evolution is a contentious, yet central topic in evolutionary biology. Analyzing 5,199 mouse genes with recorded mutant phenotypes, we find that genes exclusively affecting morphological traits when mutated (dubbed "morphogenes") are grossly enriched with transcriptional regulators, whereas those exclusively affecting physiological traits (dubbed "physiogenes") are enriched with channels, transporters, receptors, and enzymes. Compared to physiogenes, morphogenes are more likely to be essential and pleiotropic and less likely to be tissue specific. Morphogenes evolve faster in expression profile, but slower in protein sequence and gene gain/loss than physiogenes. Thus, morphological and physiological changes have a differential molecular basis; separating them helps discern the genetic mechanisms of phenotypic evolution.


Assuntos
Evolução Molecular , Perfilação da Expressão Gênica , Animais , Biologia Computacional/métodos , Bases de Dados Genéticas , Regulação da Expressão Gênica , Genômica , Humanos , Camundongos , Modelos Biológicos , Modelos Genéticos , Mutação , Hibridização de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo
15.
Biotechnol Genet Eng Rev ; : 1-12, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37232405

RESUMO

To systematically evaluate the effectiveness and safety of safinamide in the treatment of levodopa-induced motor complications of Parkinson's disease (PD). A search strategy was developed and PubMed, Embase, Web of Science, Cochrane Library, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and WanFang Data were searched to find randomized controlled trials on the treatment of PD motor complications caused by levodopa with safinamide. A manual reference search was conducted for articles published until June 2022 to independently screen references, extract data, and evaluate the risk of bias in the included studies. RevMan 5.3 software was utilized to analyze the data. A total of 5 randomized controlled trials with 2061 PD patients were included, containing 1277 patients in the safinamide group (trial group) and 784 patients in the control group. Meta-analysis results exhibited that regarding effectiveness, the duration of continuous optimal drug effect without dyskinesia (On-time) of the 50 mg trial group was longer than that of the control group. The On-time of the 100 mg trial group was longer than that of the control group.The improvement of the Unified Parkinson's Disease Rating Scale Part III (UPDRSIII) score in the 50 mg trial group was better than that in the control group. The improvement of the UPDRSIII score of the 100 mg trial group was better than that of the control group.There was no significant difference in the incidence of adverse events between the two groups. Safinamide is effective and safe in the treatment of PD motor complications caused by levodopa.

16.
World J Gastrointest Oncol ; 15(11): 1852-1863, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38077649

RESUMO

Pancreatic cancer remains one of the most lethal diseases worldwide owing to its late diagnosis, early metastasis, and poor prognosis. Because current therapeutic options are limited, there is an urgent need to investigate novel targeted treatment strategies. Pancreatic cancer faces significant metabolic challenges, principally hypoxia and nutrient deprivation, due to specific microenvironmental constraints, including an extensive desmoplastic stromal reaction. Pancreatic cancer cells have been shown to rewire their metabolism and energy production networks to support rapid survival and proliferation. Increased glucose uptake and glycolytic pathway activity during this process have been extensively described. However, growing evidence suggests that pancreatic cancer cells are glutamine addicted. As a nitrogen source, glutamine directly (or indirectly via glutamate conversion) contributes to many anabolic processes in pancreatic cancer, including amino acids, nucleobases, and hexosamine biosynthesis. It also plays an important role in redox homeostasis, and when converted to α-ketoglutarate, glutamine serves as an energy and anaplerotic carbon source, replenishing the tricarboxylic acid cycle intermediates. The present study aims to provide a comprehensive overview of glutamine metabolic reprogramming in pancreatic cancer, focusing on potential therapeutic approaches targeting glutamine metabolism in pancreatic cancer.

17.
Bioinformatics ; 27(22): 3218-9, 2011 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-21976423

RESUMO

SUMMARY: DroPhEA is a core module of a web application that facilitates research in insect functional genomics through enrichment analysis on mutant phenotypes of fruit fly (Drosophila melanogaster). The phenotypes investigated in the analyses can be predefined by FlyBase or customized by users. DroPhEA allows users to specify mutation or ortholog types, displays enriched term results in a hierarchical structure and supports analyses on gene sets of all insect species with a fully sequenced genome.


Assuntos
Drosophila melanogaster/genética , Genoma de Inseto , Fenótipo , Software , Animais , Anopheles/genética , Anopheles/fisiologia , Evolução Molecular , Comportamento Alimentar , Genes de Insetos , Genômica/métodos , Mutação
18.
Contrast Media Mol Imaging ; 2022: 8381870, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35685661

RESUMO

This study aimed to investigate the effect of berberine hydrochloride on the diversity of intestinal flora in patients with Parkinson's disease (PD). Prospectively selected 68 PD patients, admitted to our hospital from April 2021 to June 2021, were randomly assigned to an observation group and a control group (n = 34 per group). Patients in the control group were given conventional treatment in accordance with Parkinson's diagnosis and treatment guidelines. Patients in the observation group were administered berberine hydrochloride besides the treatment in the control group. After continuous treatment for 3 months, the enzyme-linked immunosorbent assay was applied to determine interleukin-8 (IL-8), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. High-throughput sequencing technology was employed to perform DNA sequencing on the 16S rRNA genes of all bacteria in stool samples before and after treatment in the two groups to analyze the distribution of intestinal flora. After treatment, the levels of IL-8, IL-6, and TNF-α were lower in the observation group than those in the control group (P < 0.05). Regarding intestinal flora, the Chao index, Ace index, and Shannon index were higher in the observation group than those in the control group. The Simpson index was lower in the observation group than that of the control group (P < 0.05). The principal component analysis chart analysis exhibited that the overall structure of the intestinal flora was quite different between the observation and the control groups after treatment. Berberine hydrochloride can improve the disorder of intestinal flora in PD patients and suppress the expression of inflammatory factors.


Assuntos
Berberina , Microbioma Gastrointestinal , Doença de Parkinson , Berberina/farmacologia , Berberina/uso terapêutico , Humanos , Interleucina-6 , Interleucina-8 , Doença de Parkinson/tratamento farmacológico , RNA Ribossômico 16S/genética , Fator de Necrose Tumoral alfa
19.
Am J Transl Res ; 14(3): 1757-1764, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35422951

RESUMO

BACKGROUND: To investigate the efficacy and safety of pramipexole in Parkinson's disease with anxiety or depression by analyzing the randomized clinical trials (RCTs). METHODS: National Library of Medicine (PubMed), Cochrane Library of EMBASE, CNKI, VIP and Wanfang database were retrieved to conduct a meta-analysis. We performed sensitivity analysis to assess the efficacy and safety of pramipexole in Parkinson's disease with anxiety or depression. RESULTS: In our study, the results showed that the efficiency was significantly improved in patients with Parkinson's disease of the experimental group (fixed effect model, SMD = 3.45, 95% CI = [2.50, 4.76]). The HAMD score of experimental group was lower than that of control group. Moreover, adverse events of experimental group were lower than that of control group. CONCLUSIONS: The research demonstrated that pramipexole may improve the efficacy and HAMD score of Parkinson's disease with anxiety or depression. Due to the limited number of included studies, more RCTs are needed to investigate the effect of pramipexole in Parkinson's disease with anxiety or depression.

20.
Bioinformatics ; 26(17): 2212-3, 2010 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-20605928

RESUMO

SUMMARY: MamPhEA is a web application dedicated to understanding functional properties of mammalian gene sets based on mouse-mutant phenotypes. It allows users to conduct enrichment analysis on predefined or user-defined phenotypes, gives users the option to specify phenotypes derived from null mutations, produces easily comprehensible results and supports analyses on genes of all mammalian species with a fully sequenced genome. AVAILABILITY: http://evol.nhri.org.tw/MamPhEA/.


Assuntos
Internet , Fenótipo , Software , Animais , Bases de Dados Genéticas , Expressão Gênica , Camundongos , Mutação
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