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1.
Nature ; 623(7987): 562-570, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37880372

RESUMO

Vision enables both image-forming perception, driven by a contrast-based pathway, and unconscious non-image-forming circadian photoentrainment, driven by an irradiance-based pathway1,2. Although two distinct photoreceptor populations are specialized for each visual task3-6, image-forming photoreceptors can additionally contribute to photoentrainment of the circadian clock in different species7-15. However, it is unknown how the image-forming photoreceptor pathway can functionally implement the segregation of irradiance signals required for circadian photoentrainment from contrast signals required for image perception. Here we report that the Drosophila R8 photoreceptor separates image-forming and irradiance signals by co-transmitting two neurotransmitters, histamine and acetylcholine. This segregation is further established postsynaptically by histamine-receptor-expressing unicolumnar retinotopic neurons and acetylcholine-receptor-expressing multicolumnar integration neurons. The acetylcholine transmission from R8 photoreceptors is sustained by an autocrine negative feedback of the cotransmitted histamine during the light phase of light-dark cycles. At the behavioural level, elimination of histamine and acetylcholine transmission impairs R8-driven motion detection and circadian photoentrainment, respectively. Thus, a single type of photoreceptor can achieve the dichotomy of visual perception and circadian photoentrainment as early as the first visual synapses, revealing a simple yet robust mechanism to segregate and translate distinct sensory features into different animal behaviours.


Assuntos
Ritmo Circadiano , Drosophila melanogaster , Células Fotorreceptoras de Invertebrados , Percepção Visual , Animais , Acetilcolina/metabolismo , Relógios Biológicos/fisiologia , Relógios Biológicos/efeitos da radiação , Ritmo Circadiano/fisiologia , Ritmo Circadiano/efeitos da radiação , Drosophila melanogaster/citologia , Drosophila melanogaster/fisiologia , Drosophila melanogaster/efeitos da radiação , Retroalimentação Fisiológica , Histamina/metabolismo , Neurotransmissores/metabolismo , Células Fotorreceptoras de Invertebrados/metabolismo , Células Fotorreceptoras de Invertebrados/efeitos da radiação , Receptores Colinérgicos/metabolismo , Receptores Histamínicos/metabolismo , Percepção Visual/fisiologia , Percepção Visual/efeitos da radiação
2.
Nature ; 588(7837): 284-289, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33239781

RESUMO

Genetic diversity is key to crop improvement. Owing to pervasive genomic structural variation, a single reference genome assembly cannot capture the full complement of sequence diversity of a crop species (known as the 'pan-genome'1). Multiple high-quality sequence assemblies are an indispensable component of a pan-genome infrastructure. Barley (Hordeum vulgare L.) is an important cereal crop with a long history of cultivation that is adapted to a wide range of agro-climatic conditions2. Here we report the construction of chromosome-scale sequence assemblies for the genotypes of 20 varieties of barley-comprising landraces, cultivars and a wild barley-that were selected as representatives of global barley diversity. We catalogued genomic presence/absence variants and explored the use of structural variants for quantitative genetic analysis through whole-genome shotgun sequencing of 300 gene bank accessions. We discovered abundant large inversion polymorphisms and analysed in detail two inversions that are frequently found in current elite barley germplasm; one is probably the product of mutation breeding and the other is tightly linked to a locus that is involved in the expansion of geographical range. This first-generation barley pan-genome makes previously hidden genetic variation accessible to genetic studies and breeding.


Assuntos
Cromossomos de Plantas/genética , Genoma de Planta/genética , Hordeum/genética , Internacionalidade , Mutação , Melhoramento Vegetal , Inversão Cromossômica/genética , Mapeamento Cromossômico , Loci Gênicos/genética , Genótipo , Hordeum/classificação , Polimorfismo Genético/genética , Padrões de Referência , Banco de Sementes , Inversão de Sequência , Sequenciamento Completo do Genoma
3.
J Cell Mol Med ; 27(2): 189-203, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36541023

RESUMO

Circular RNAs (circRNAs) are often found in eukaryocyte and have a role in the pathogenesis of a variety of human disorders. Our related research has shown the differential expression of circRNAs in periprosthetic osteolysis (PPOL). However, the involvement of circRNAs in the exact process is yet unknown. CircSLC8A1 expression was evaluated in clinical samples and human bone marrow mesenchymal stem cells (hBMSCs) in this investigation using quantitative real-time PCR. In vitro and in vivo studies were conducted to explicate its functional role and pathway. We demonstrated CircSLC8A1 is involved in PPOL using gain- and loss-of-function methods. The association of CircSLC8A1 and miR-144-3p, along with miR-144-3p and RUNX1, was predicted using bioinformatics. RNA pull-down and luciferase assays confirmed it. The impact of CircSLC8A1 in the PPOL-mouse model was also investigated using adeno-associated virus. CircSLC8A1 was found to be downregulated in PPOL patients' periprosthetic tissues. Overexpression of CircSLC8A1 promoted osteogenic differentiation (OD) and inhibited apoptosis of hBMSCs in vitro. The osteogenic markers of RUNX1, osteopontin (OPN) and osteocalcin (OCN) were significantly upregulated in hBMSCs after miR-144-3p inhibitor was transferred. Mechanistic analysis demonstrated that CircSLC8A1 directly bound to miR-144-3p and participated in PPOL through the miR-144-3p/RUNX1 pathway in hBMSCs. Micro-CT and quantitative analysis showed that CircSLC8A1 markedly inhibited PPOL, and osteogenic markers (RUNX1, OPN and OCN) were significantly increased (P<0.05) in the mice model. Our findings prove that CircSLC8A1 exerted a regulatory role in promoting osteogenic differentiation in hBMSCs, and CircSLC8A1/miR-144-3p/RUNX1 pathway may provide a potential target for prevention of PPOL.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Osteólise , Animais , Camundongos , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Osteogênese/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Osteólise/genética , Osteólise/metabolismo , Diferenciação Celular/genética , Células-Tronco Mesenquimais/metabolismo , Osteocalcina/metabolismo , Células Cultivadas
4.
Plant Biotechnol J ; 21(1): 46-62, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36054248

RESUMO

Divergent selection of populations in contrasting environments leads to functional genomic divergence. However, the genomic architecture underlying heterogeneous genomic differentiation remains poorly understood. Here, we de novo assembled two high-quality wild barley (Hordeum spontaneum K. Koch) genomes and examined genomic differentiation and gene expression patterns under abiotic stress in two populations. These two populations had a shared ancestry and originated in close geographic proximity but experienced different selective pressures due to their contrasting micro-environments. We identified structural variants that may have played significant roles in affecting genes potentially associated with well-differentiated phenotypes such as flowering time and drought response between two wild barley genomes. Among them, a 29-bp insertion into the promoter region formed a cis-regulatory element in the HvWRKY45 gene, which may contribute to enhanced tolerance to drought. A single SNP mutation in the promoter region may influence HvCO5 expression and be putatively linked to local flowering time adaptation. We also revealed significant genomic differentiation between the two populations with ongoing gene flow. Our results indicate that SNPs and small SVs link to genetic differentiation at the gene level through local adaptation and are maintained through divergent selection. In contrast, large chromosome inversions may have shaped the heterogeneous pattern of genomic differentiation along the chromosomes by suppressing chromosome recombination and gene flow. Our research offers novel insights into the genomic basis underlying local adaptation and provides valuable resources for the genetic improvement of cultivated barley.


Assuntos
Hordeum , Hordeum/genética , Genômica , Adaptação Fisiológica/genética , Genes de Plantas
5.
Anal Biochem ; 663: 115020, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36521558

RESUMO

X-ray crystallography is the major approach for atomic-level protein structure determination. Since not all proteins can be easily crystallized, accurate prediction of protein crystallization propensity is critical to guiding the experimental design and improving the success rate of X-ray crystallography experiments. In this work, we proposed a new deep learning pipeline, GCmapCrys, for multi-stage crystallization propensity prediction through integrating graph attention network with predicted protein contact map. Experimental results on 1548 proteins with known crystallization records demonstrated that GCmapCrys increased the value of Matthew's correlation coefficient by 37.0% in average compared to state-of-the-art protein crystallization propensity predictors. Detailed analyses show that the major advantages of GCmapCrys lie in the efficiency of the graph attention network with predicted contact map, which effectively associates the residue-interaction knowledge with crystallization pattern. Meanwhile, the designed four sequence-based features can be complementary to further enhance crystallization propensity proprediction.


Assuntos
Biologia Computacional , Proteínas , Cristalização/métodos , Proteínas/química , Cristalografia por Raios X , Biologia Computacional/métodos
6.
Virol J ; 20(1): 270, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37990229

RESUMO

BACKGROUND: Influenza A virus (IAV) is the only influenza virus causing flu pandemics (i.e., global epidemics of flu disease). Influenza (the flu) is a highly contagious disease that can be deadly, especially in high-risk groups. Worldwide, these annual epidemics are estimated to result in about 3 to 5 million cases of severe illness and in about 290,000 to 650,000 respiratory deaths. We intend to reveal the effect of IAV infection on the host's metabolism, immune response, and neurotoxicity by using a mouse IAV infection model. METHODS: 51 metabolites of murine blood plasma (33 amino acids/amino acid derivatives (AADs) and 18 metabolites of the tryptophan pathway) were analyzed by using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry with Electrospray Ionization at the acute (7 days post-infection (dpi)), resolution (14 dpi), and recovery (21 dpi) stages of the virus infection in comparison with controls. RESULTS: Among the 33 biogenic amino acids/AADs, the levels of five amino acids/AADs (1-methylhistidine, 5-oxoproline, α-aminobutyric acid, glutamine, and taurine) increased by 7 dpi, whereas the levels of ten amino acids/AADs (4-hydroxyproline, alanine, arginine, asparagine, cysteine, citrulline, glycine, methionine, proline, and tyrosine) decreased. By 14 dpi, the levels of one AAD (3-methylhistidine) increased, whereas the levels of five amino acids/AADs (α-aminobutyric acid, aminoadipic acid, methionine, threonine, valine) decreased. Among the 18 metabolites from the tryptophan pathway, the levels of kynurenine, quinolinic acid, hydroxykynurenine increased by 7 dpi, whereas the levels of indole-3-acetic acid and nicotinamide riboside decreased. CONCLUSIONS: Our data may facilitate understanding the molecular mechanisms of host responses to IAV infection and provide a basis for discovering potential new mechanistic, diagnostic, and prognostic biomarkers and therapeutic targets for IAV infection.


Assuntos
Vírus da Influenza A , Influenza Humana , Animais , Camundongos , Humanos , Triptofano , Aminoácidos/metabolismo , Metionina , Vírus da Influenza A/metabolismo
7.
Nature ; 544(7651): 427-433, 2017 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-28447635

RESUMO

Cereal grasses of the Triticeae tribe have been the major food source in temperate regions since the dawn of agriculture. Their large genomes are characterized by a high content of repetitive elements and large pericentromeric regions that are virtually devoid of meiotic recombination. Here we present a high-quality reference genome assembly for barley (Hordeum vulgare L.). We use chromosome conformation capture mapping to derive the linear order of sequences across the pericentromeric space and to investigate the spatial organization of chromatin in the nucleus at megabase resolution. The composition of genes and repetitive elements differs between distal and proximal regions. Gene family analyses reveal lineage-specific duplications of genes involved in the transport of nutrients to developing seeds and the mobilization of carbohydrates in grains. We demonstrate the importance of the barley reference sequence for breeding by inspecting the genomic partitioning of sequence variation in modern elite germplasm, highlighting regions vulnerable to genetic erosion.


Assuntos
Cromossomos de Plantas/genética , Genoma de Planta/genética , Hordeum/genética , Núcleo Celular/genética , Centrômero/genética , Cromatina/genética , Cromatina/metabolismo , Mapeamento Cromossômico , Cromossomos Artificiais Bacterianos/genética , Variação Genética , Genômica , Haplótipos/genética , Meiose/genética , Sequências Repetitivas de Ácido Nucleico/genética , Sementes/genética
8.
BMC Med Educ ; 23(1): 323, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37158861

RESUMO

BACKGROUND: Massive open online courses (MOOCs) have become innovative open-learning approach in medical education. This study aimed to evaluate the dynamic changes in the construction and application of medical MOOCs before and after the coronavirus disease 2019 (COVID-19) pandemic in China. METHODS: The dynamic changes of usages about medical MOOCs before and after 2020 were mainly searched on the Smart Education of China Higher Education platform, and the detailed learning profiles and outcome indicators were further analyzed using 40 national first-class medical MOOCs from 'zhihuishu' platform. RESULTS: A total of 2,405 medical MOOCs were exported from the Smart Education of China Higher Education platform, of which 1,313 (54.6%) were launched since 2020. The total and average numbers of participants of 141 national first-class medical MOOCs peaked during the initial spread of COVID-19 in 2020. We further analyzed the dynamic usage of MOOCs from 2018 to 2022 based on 40 national first-class medical MOOCs launched on the 'Zhihuishu' platform. The findings revealed that the number of registered learners (3,240 versus 2,654), questions and answers (27,005 versus 5,116) and students taking the final examination (2,782 versus 1,995) per semester were significantly higher since 2020 compared to these before 2020. Especially, the number of registered learners, registered schools, questions and answers, and students participating in online discussion, taking the unit quiz, taking final examinations and passing final examinations all peaked in the 2020 spring-summer semester. Pearson's correlation analysis found that the number of questions and answers and the number of learners who participated in online discussion were both positively correlated with the number of students who passed the final examination, and the correlation was especially strong since 2020. Moreover, the number of publications on medical MOOC research has soared since 2020 and has maintained a continuous upward trend. CONCLUSIONS: High-quality medical MOOCs have been launched rapidly since the COVID-19 pandemic in China. The number of participants and online interactions of medical MOOCs peaked during the initial spread of COVID-19 in 2020. MOOCs are reliable and valid digital sources that facilitate medical higher education and play irreplaceable roles in emergency management.


Assuntos
COVID-19 , Educação a Distância , Humanos , Pandemias , COVID-19/epidemiologia , Escolaridade , China/epidemiologia
9.
Alzheimers Dement ; 19(4): 1117-1134, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36574591

RESUMO

INTRODUCTION: Plasma amyloid beta (Aß)1-42/Aß1-40 ratio, phosphorylated-tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) are putative blood biomarkers for Alzheimer's disease (AD). However, head-to-head cross-sectional and longitudinal comparisons of the aforementioned biomarkers across the AD continuum are lacking. METHODS: Plasma Aß1-42, Aß1-40, p-tau181, GFAP, and NfL were measured utilizing the Single Molecule Array (Simoa) platform and compared cross-sectionally across the AD continuum, wherein Aß-PET (positron emission tomography)-negative cognitively unimpaired (CU Aß-, n = 81) and mild cognitive impairment (MCI Aß-, n = 26) participants were compared with Aß-PET-positive participants across the AD continuum (CU Aß+, n = 39; MCI Aß+, n = 33; AD Aß+, n = 46) from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) cohort. Longitudinal plasma biomarker changes were also assessed in MCI (n = 27) and AD (n = 29) participants compared with CU (n = 120) participants. In addition, associations between baseline plasma biomarker levels and prospective cognitive decline and Aß-PET load were assessed over a 7 to 10-year duration. RESULTS: Lower plasma Aß1-42/Aß1-40 ratio and elevated p-tau181 and GFAP were observed in CU Aß+, MCI Aß+, and AD Aß+, whereas elevated plasma NfL was observed in MCI Aß+ and AD Aß+, compared with CU Aß- and MCI Aß-. Among the aforementioned plasma biomarkers, for models with and without AD risk factors (age, sex, and apolipoprotein E (APOE) ε4 carrier status), p-tau181 performed equivalent to or better than other biomarkers in predicting a brain Aß-/+ status across the AD continuum. However, for models with and without the AD risk factors, a biomarker panel of Aß1-42/Aß1-40, p-tau181, and GFAP performed equivalent to or better than any of the biomarkers alone in predicting brain Aß-/+ status across the AD continuum. Longitudinally, plasma Aß1-42/Aß1-40, p-tau181, and GFAP were altered in MCI compared with CU, and plasma GFAP and NfL were altered in AD compared with CU. In addition, lower plasma Aß1-42/Aß1-40 and higher p-tau181, GFAP, and NfL were associated with prospective cognitive decline and lower plasma Aß1-42/Aß1-40, and higher p-tau181 and GFAP were associated with increased Aß-PET load prospectively. DISCUSSION: These findings suggest that plasma biomarkers are altered cross-sectionally and longitudinally, along the AD continuum, and are prospectively associated with cognitive decline and brain Aß-PET load. In addition, although p-tau181 performed equivalent to or better than other biomarkers in predicting an Aß-/+ status across the AD continuum, a panel of biomarkers may have superior Aß-/+ status predictive capability across the AD continuum. HIGHLIGHTS: Area under the curve (AUC) of p-tau181 ≥ AUC of Aß42/40, GFAP, NfL in predicting PET Aß-/+ status (Aß-/+).  AUC of Aß42/40+p-tau181+GFAP panel ≥ AUC of Aß42/40/p-tau181/GFAP/NfL for Aß-/+.  Longitudinally, Aß42/40, p-tau181, and GFAP were altered in MCI versus CU.  Longitudinally, GFAP and NfL were altered in AD versus CU.  Aß42/40, p-tau181, GFAP, and NfL are associated with prospective cognitive decline.  Aß42/40, p-tau181, and GFAP are associated with increased PET Aß load prospectively.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides , Proteína Glial Fibrilar Ácida , Estudos Transversais , Filamentos Intermediários , Estudos Longitudinais , Estudos Prospectivos , Austrália , Apolipoproteína E4 , Disfunção Cognitiva/diagnóstico por imagem , Biomarcadores , Proteínas tau
10.
Int J Mol Sci ; 24(10)2023 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-37240406

RESUMO

The quality and maturation of an oocyte not only play decisive roles in fertilization and embryo success, but also have long-term impacts on the later growth and development of the fetus. Female fertility declines with age, reflecting a decline in oocyte quantity. However, the meiosis of oocytes involves a complex and orderly regulatory process whose mechanisms have not yet been fully elucidated. This review therefore mainly focuses on the regulation mechanism of oocyte maturation, including folliculogenesis, oogenesis, and the interactions between granulosa cells and oocytes, plus in vitro technology and nuclear/cytoplasm maturation in oocytes. Additionally, we have reviewed advances made in the single-cell mRNA sequencing technology related to oocyte maturation in order to improve our understanding of the mechanism of oocyte maturation and to provide a theoretical basis for subsequent research into oocyte maturation.


Assuntos
Oócitos , Oogênese , Animais , Feminino , Oogênese/genética , Oócitos/fisiologia , Mamíferos , Meiose , Células da Granulosa
11.
Plant J ; 106(2): 419-434, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33506596

RESUMO

The future of plant cultivar improvement lies in the evaluation of genetic resources from currently available germplasm. Today's gene pool of crop genetic diversity has been shaped during domestication and more recently by breeding. Recent efforts in plant breeding have been aimed at developing new and improved varieties from poorly adapted crops to suit local environments. However, the impact of these breeding efforts is poorly understood. Here, we assess the contributions of both historical and recent breeding efforts to local adaptation and crop improvement in a global barley panel by analysing the distribution of genetic variants with respect to geographic region or historical breeding category. By tracing the impact that breeding had on the genetic diversity of Hordeum vulgare (barley) released in Australia, where the history of barley production is relatively young, we identify 69 candidate regions within 922 genes that were under selection pressure. We also show that modern Australian barley varieties exhibit 12% higher genetic diversity than historical cultivars. Finally, field-trialling and phenotyping for agriculturally relevant traits across a diverse range of Australian environments suggests that genomic regions under strong breeding selection and their candidate genes are closely associated with key agronomic traits. In conclusion, our combined data set and germplasm collection provide a rich source of genetic diversity that can be applied to understanding and improving environmental adaptation and enhanced yields.


Assuntos
Genoma de Planta/genética , Hordeum/genética , Melhoramento Vegetal , Austrália , Produção Agrícola , Domesticação , Genes de Plantas/genética , Variação Genética
12.
Plant J ; 105(5): 1192-1210, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33249667

RESUMO

Shifting from a livestock-based protein diet to a plant-based protein diet has been proposed as an essential requirement to maintain global food sustainability, which requires the increased production of protein-rich crops for direct human consumption. Meanwhile, the lack of sufficient genetic diversity in crop varieties is an increasing concern for sustainable food supplies. Countering this concern requires a clear understanding of the domestication process and dynamics. Narrow-leafed lupin (Lupinus angustifolius L.) has experienced rapid domestication and has become a new legume crop over the past century, with the potential to provide protein-rich seeds. Here, using long-read whole-genome sequencing, we assembled the third-generation reference genome for the narrow-leafed lupin cultivar Tanjil, comprising 20 chromosomes with a total genome size of 615.8 Mb and contig N50 = 5.65 Mb. We characterized the original mutation and putative biological pathway resulting in low seed alkaloid level that initiated the recent domestication of narrow-leafed lupin. We identified a 1133-bp insertion in the cis-regulatory region of a putative gene that may be associated with reduced pod shattering (lentus). A comparative analysis of genomic diversity in cultivars and wild types identified an apparent domestication bottleneck, as precisely predicted by the original model of the bottleneck effect on genetic variability in populations. Our results identify the key domestication genetic loci and provide direct genomic evidence for a domestication bottleneck, and open up the possibility of knowledge-driven de novo domestication of wild plants as an avenue to broaden crop plant diversity to enhance food security and sustainable low-carbon emission agriculture.


Assuntos
Genoma de Planta/genética , Lupinus/genética , Folhas de Planta/genética , Variação Genética/genética , Mutação/genética
13.
J Neurochem ; 163(1): 53-67, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36000528

RESUMO

Cholesterol levels have been repeatedly linked to Alzheimer's Disease (AD), suggesting that high levels could be detrimental, but this effect is likely attributed to Low-Density Lipoprotein (LDL) cholesterol. On the other hand, High-Density Lipoproteins (HDL) cholesterol levels have been associated with reduced brain amyloidosis and improved cognitive function. However, recent findings have suggested that HDL-functionality, which depends upon the HDL-cargo proteins associated with HDL, rather than HDL levels, appears to be the key factor, suggesting a quality over quantity status. In this report, we have assessed the HDL-cargo (Cholesterol, ApoA-I, ApoA-II, ApoC-I, ApoC-III, ApoD, ApoE, ApoH, ApoJ, CRP, and SAA) in stable healthy control (HC), healthy controls who will convert to MCI/AD (HC-Conv) and AD patients (AD). Compared to HC we observed an increased cholesterol/ApoA-I ratio in AD and HC-Conv, as well as an increased ApoD/ApoA-I ratio and a decreased ApoA-II/ApoA-I ratio in AD. Higher cholesterol/ApoA-I ratio was also associated with lower cortical grey matter volume and higher ventricular volume, while higher ApoA-II/ApoA-I and ApoJ/ApoA-I ratios were associated with greater cortical grey matter volume (and for ApoA-II also with greater hippocampal volume) and smaller ventricular volume. Additionally, in a clinical status-independent manner, the ApoE/ApoA-I ratio was significantly lower in APOE ε4 carriers and lowest in APOE ε4 homozygous. Together, these data indicate that in AD patients the composition of HDL is altered, which may affect HDL functionality, and such changes are associated with altered regional brain volumetric data.


Assuntos
Doença de Alzheimer , Lipoproteínas HDL , Apolipoproteína A-I/metabolismo , Apolipoproteína A-II/metabolismo , Apolipoproteína C-III/metabolismo , Apolipoproteína E4/metabolismo , Apolipoproteínas E/metabolismo , Encéfalo/metabolismo , Colesterol/metabolismo , Humanos , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo
14.
Inorg Chem ; 61(43): 17196-17201, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36265225

RESUMO

Semiconductor conductivities depend largely on the crystal structures and the associated electronic structures. If the electronic structures can be switched reversibly in the same crystal structure, then a drastic conductivity change may be controllable. The effect of electron transfer (ET) on semiconductor conductivity remained elusive so far. In this work, a series of two pillared inorganicorganic hybrid photochromic semiconductors (PSCs), [(CQ)Pb3X6(H2O)]·2H2O [X = Cl (1) and Br (2), CQ = N-4,4'-bipyridiniopropionate (viologen)], with II-stacking viologen π-aggregates, are constructed by a bottom-up self-assembly strategy through inorganic skeleton-directed intercalation and intermolecular noncovalent interaction. The conductivities are abnormally "invariant" after photoinduced ET, breaking the convention that the generation of radicals favors conductivity. The abnormally "invariant" conductivities are mainly derived from approximate electronic couplings before and after ET between II-stacking viologen π-aggregates.

15.
J Chem Inf Model ; 62(17): 4283-4291, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36017565

RESUMO

Protein fold recognition refers to predicting the most likely fold type of the query protein and is a critical step of protein structure and function prediction. With the popularity of deep learning in bioinformatics, protein fold recognition has obtained impressive progress. In this study, to extract the fold-specific feature to improve protein fold recognition, we proposed a unified deep metric learning framework based on a joint loss function, termed NPCFold. In addition, we also proposed an integrated machine learning model based on the similarity of proteins in various properties, termed NPCFoldpro. Benchmark experiments show both NPCFold and NPCFoldpro outperform existing protein fold recognition methods at the fold level, indicating that our proposed strategies of fusing loss functions and fusing features could improve the fold recognition level.


Assuntos
Biologia Computacional , Proteínas , Biologia Computacional/métodos , Aprendizado de Máquina , Proteínas/química
16.
Cell Mol Biol (Noisy-le-grand) ; 68(6): 124-129, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-36227667

RESUMO

This experiment was carried out to study the effects of estrogen on the proliferation and apoptosis of osteoblasts through regulating the G protein-coupled estrogen receptor (GPER)/protein kinase B (AKT) pathway. For this aim, osteoblasts were cultured in vitro and divided into control group, estrogen group and inhibitor group after passage. The osteoblasts in the control group were cultured normally, estrogen intervention was made in the estrogen group and G15 inhibitor intervention was made in the inhibitor group. After intervention for 24 h, osteoblasts were collected for detection. The positive expression of GPER and the double-positive expression of Tom20/Lamp2 were detected via immunofluorescence assay. The protein expressions of GPER, AKT and phosphorylated (p)-AKT were detected via Western blotting. The mRNA expression of GPER was detected via qPCR. Moreover, the autophagosomes were observed under a transmission electron microscope, and the apoptosis and cell proliferation were detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and cell counting kit-8 (CCK8) assay, respectively. Results of the immunofluorescence assay revealed that the positive expression of GPER in the estrogen group was higher than that in the control group and inhibitor group (p<0.05), while the double-positive expression of Tom20/Lamp2 in the estrogen group was lower than that in control group and inhibitor group (p<0.05). According to the results of Western blotting, the relative protein expression of AKT had no differences among the three groups (p>0.05), while the relative protein expressions of GPER and p-AKT in the estrogen group were higher than those in the control group and inhibitor group (p<0.05). The results of qPCR showed that the relative mRNA expression of GPER in the estrogen group was higher than that in the control group and inhibitor group (p<0.05). There were a small number of autophagosomes in osteoblasts in the control group and inhibitor group, while the number of autophagosomes in osteoblasts was smaller in the estrogen group. Besides, the estrogen group had a remarkably lower apoptosis rate of osteoblasts than the control group and inhibitor group and a remarkably higher proliferation rate than the control group and inhibitor group. Then estrogen can inhibit the mitochondrial autophagy of osteoblasts by regulating the GPER/AKT pathway, thereby inhibiting apoptosis and promoting cell proliferation.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Receptores de Estrogênio , Apoptose , Proliferação de Células , DNA Nucleotidilexotransferase/metabolismo , DNA Nucleotidilexotransferase/farmacologia , Estrogênios/farmacologia , Proteínas de Ligação ao GTP/metabolismo , Osteoblastos/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais
17.
Bull Entomol Res ; 112(2): 187-196, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34474703

RESUMO

Diadegma semiclausum is an important parasitoid wasp and widely used in the biological control of the diamondback moth, Plutella xylostella, one of the most destructive pests of cruciferous plants. Insect olfactory system is critical in guiding behaviors including feeding, mating, and oviposition, in which odorant binding proteins (OBPs) and odorant receptors (ORs) are two key components. However, limited attention has been paid to D. semiclausum olfactory genes. In this study, a transcriptome sequencing was performed on the RNA samples extracted from D. semiclausum male and female adult antennae. A total of 17 putative OBP and 67 OR genes were annotated and further compared to OBPs and ORs from P. xylostella, and other hemipteran parasitoid species. The expression patterns of D. semiclausum OBPs between male and female antennae were examined using reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR. Six OBPs (DsemOBP 6, 7, 8, 9, 10, and 14) demonstrated significantly higher expression levels in females than in males, which may assist in female D. semiclausum host-seeking and oviposition behaviors. This study advances our understanding of the olfactory system of D. semiclausum at the molecular level and paves the way for future functional studies aiming at increasing the efficacy to control P. xylostella by using D. semiclausum.


Assuntos
Mariposas , Vespas , Animais , Antenas de Artrópodes/metabolismo , Feminino , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Larva/fisiologia , Masculino , Mariposas/genética , Oviposição , Olfato , Vespas/genética
18.
Plant J ; 101(5): 1057-1074, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31571294

RESUMO

Functional divergence after gene duplication plays a central role in plant evolution. Among cereals, only Hordeum vulgare (barley), Triticum aestivum (wheat) and Secale cereale (rye) accumulate delphinidin-derived (blue) anthocyanins in the aleurone layer of grains, whereas Oryza sativa (rice), Zea mays (maize) and Sorghum bicolor (sorghum) do not. The underlying genetic basis for this natural occurrence remains elusive. Here, we mapped the barley Blx1 locus involved in blue aleurone to an approximately 1.13 Mb genetic interval on chromosome 4HL, thus identifying a trigenic cluster named MbHF35 (containing HvMYB4H, HvMYC4H and HvF35H). Sequence and expression data supported the role of these genes in conferring blue-coloured (blue aleurone) grains. Synteny analyses across monocot species showed that MbHF35 has only evolved within distinct Triticeae lineages, as a result of dispersed gene duplication. Phylogeny analyses revealed a shared evolution pattern for MbHF35 in Triticeae, suggesting that these genes have co-evolved together. We also identified a Pooideae-specific flavonoid 3',5'-hydroxylase (F3'5'H) lineage, termed here Mo_F35H2, which has a higher amino acid similarity with eudicot F3'5'Hs, demonstrating a scenario of convergent evolution. Indeed, selection tests identified 13 amino acid residues in Mo_F35H2 that underwent positive selection, possibly driven by protein thermostablility selection. Furthermore, through the interrogation of barley germplasm there is evidence that HvMYB4H and HvMYC4H have undergone human selection. Collectively, our study favours blue aleurone as a recently evolved trait resulting from environmental adaptation. Our findings provide an evolutionary explanation for the absence of blue anthocyanins in other cereals and highlight the importance of gene functional divergence for plant diversity and environmental adaptation.


Assuntos
Hordeum/genética , Proteínas de Plantas/genética , Adaptação Fisiológica/genética , Evolução Biológica , Mapeamento Cromossômico , Cor , Grão Comestível , Meio Ambiente , Duplicação Gênica , Loci Gênicos/genética , Hordeum/fisiologia , Fenótipo , Filogenia , Proteínas de Plantas/metabolismo
19.
Theor Appl Genet ; 134(9): 2875-2889, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34059938

RESUMO

KEY MESSAGE: Using genomic structural equation modelling, this research demonstrates an efficient way to identify genetically correlating traits and provides an effective proxy for multi-trait selection to consider the joint genetic architecture of multiple interacting traits in crop breeding. Breeding crop cultivars with optimal value across multiple traits has been a challenge, as traits may negatively correlate due to pleiotropy or genetic linkage. For example, grain yield and grain protein content correlate negatively with each other in cereal crops. Future crop breeding needs to be based on practical yet accurate evaluation and effective selection of beneficial trait to retain genes with the best agronomic score for multiple traits. Here, we test the framework of whole-system-based approach using structural equation modelling (SEM) to investigate how one trait affects others to guide the optimal selection of a combination of agronomically important traits. Using ten traits and genome-wide SNP profiles from a worldwide barley panel and SEM analysis, we revealed a network of interacting traits, in which tiller number contributes positively to both grain yield and protein content; we further identified common genetic factors affecting multiple traits in the network of interaction. Our method demonstrates an efficient way to identify genetically correlating traits and underlying pleiotropic genetic factors and provides an effective proxy for multi-trait selection within a whole-system framework that considers the joint genetic architecture of multiple interacting traits in crop breeding. Our findings suggest the promise of a whole-system approach to overcome challenges such as the negative correlation of grain yield and protein content to facilitating quantitative and objective breeding decisions in future crop breeding.


Assuntos
Cromossomos de Plantas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/genética , Genoma de Planta , Melhoramento Vegetal/métodos , Locos de Características Quantitativas , Seleção Genética , Mapeamento Cromossômico/métodos , Polimorfismo de Nucleotídeo Único
20.
Int J Med Sci ; 18(3): 768-777, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33437212

RESUMO

Increasing evidence has demonstrated that circular RNA (circRNA) exerts important function in the pathogenesis of some diseases. While, the contributions of circRNAs to aseptic loosening after total hip arthroplasty (THA) remain largely unknown. Our research is to explore the differentially expressed circRNAs (DEcircRNAs) and elucidate complex regulated mechanism of circRNAs in aseptic loosening. The DEcircRNAs were identified by RNA sequencing (RNA-seq) analysis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was adopted to corroborate these DEcircRNAs. The potential function of circRNAs in aseptic loosening tissue was identified by competing endogenous RNA (ceRNA) analysis. Enrichment analysis was performed for target mRNAs and host genes of the DEcircRNAs by Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). 257 DEcircRNAs were obtained from RNA-seq results. Following the RT-qPCR corroboration, 6 circRNAs (hsa_circ_0007482, hsa_circ_0005232, hsa_circ_0000994, hsa_circ_0000690, hsa_circ_0058092 and hsa_circ_0004496) were selected for further analysis. By circRNA-miRNA and miRNA-mRNA prediction, 6 circRNAs, 138 miRNAs and 1667 mRNAs were identified. Then, circRNA-miRNA-mRNA network was established. The result of GO and KEGG enrichment analysis suggested that the circRNAs were related with some biological functions and pathways of aseptic loosening. A novel pathogenesis and treatment strategy about aseptic loosening after THA was revealed from our study of circRNA-miRNA-mRNA network.


Assuntos
Artroplastia de Quadril/efeitos adversos , Regulação da Expressão Gênica/imunologia , Redes Reguladoras de Genes/imunologia , Falha de Prótese , RNA Circular/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA-Seq , Reoperação , Membrana Sinovial/imunologia , Membrana Sinovial/patologia
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