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1.
Reprod Sci ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34622427

RESUMO

Preeclampsia (PE) is a hypertensive pregnancy, which is a leading cause of maternal and fetal morbidity and mortality during pregnancy. L-Tryptophan (Trp) is an essential amino acid, which can be metabolized into various biologically active metabolites. However, the levels of many circulating Trp-metabolites in human normotensive pregnancies (NT) and PE are undetermined. This study quantified the levels of Trp-metabolites in maternal and umbilical vein sera from women with NT and PE. Paired maternal and umbilical blood samples were collected from singleton pregnant patients. Twenty-five Trp-metabolites were measured in serum samples using liquid chromatography with tandem mass spectrometry. The effects of L-kynurenine (Kyn) and indole-3-lactic acid (ILA), on function of human umbilical vein endothelial cells (HUVECs), were also determined. Twenty Trp-metabolites were detected. The levels of 9 Trp-metabolites including Kyn and ILA were higher (P < 0.05) in umbilical vein than maternal serum, whereas 2 (5-hydroxy-L-tryptophan and serotonin) were lower (P < 0.05) in umbilical vein compared to maternal serum. PE significantly (P < 0.05) elevated ILA levels in maternal and umbilical vein sera. Kyn dose-dependently decreased (P < 0.05) cell viability. Kyn and ILA dose- and time-dependently (P < 0.05) increased monolayer integrity in HUVECs. These data suggest that these Trp-metabolites are important in regulating endothelial function during pregnancy, and the elevated ILA in PE may antagonize increased endothelial permeability occurring in PE.

2.
BMC Biol ; 19(1): 222, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625063

RESUMO

BACKGROUND: The zinc-finger transcription factor Krüppel-homolog 1 (Kr-h1) exerts a dual regulatory role during insect development by preventing precocious larval/nymphal metamorphosis and in stimulating aspects of adult reproduction such as vitellogenesis. However, how Kr-h1 functions both as a transcriptional repressor in juvenile metamorphosis and an activator in adult reproduction remains elusive. Here, we use the insect Locusta migratoria to dissect the molecular mechanism by which Kr-h1 functions as activator and repressor at these distinct developmental stages. RESULTS: We report that the kinase PKCα triggers Kr-h1 phosphorylation at the amino acid residue Ser154, a step essential for its dual functions. During juvenile stage, phosphorylated Kr-h1 recruits a corepressor, C-terminal binding protein (CtBP). The complex of phosphorylated Kr-h1 and CtBP represses the transcription of Ecdysone induced protein 93F (E93) and consequently prevents the juvenile-to-adult transition. In adult insects, phosphorylated Kr-h1 recruits a coactivator, CREB-binding protein (CBP), and promotes vitellogenesis by inducing the expression of Ribosomal protein L36. Furthermore, Kr-h1 phosphorylation with the concomitant inhibition of E93 transcription is evolutionarily conserved across insect orders. CONCLUSION: Our results suggest that Kr-h1 phosphorylation is indispensable for the recruitment of transcriptional cofactors, and for its anti-metamorphic and vitellogenic actions in insects. Our data shed new light on the understanding of Kr-h1 regulation and function in JH-regulated insect metamorphosis and reproduction.

3.
Luminescence ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34634179

RESUMO

Cr (VI) is a kind of dangerous effluent which has great harm to human health and environment. Recognition and perception of Cr (VI) by artificial receptors has attracted extensive attention. A novel fluorescent chemical sensor based on 5,7-dihydroxyflavone skeleton was designed and synthesized for the selective recognition of Cr (VI). As confirmed by fluorescence technology, the fluorescent probe 4-dimethylaminobenzyl chrysin ester-Zn (DBC-Zn) showed high sensitivity and selectivity for dichromate and fast response (less than 30 seconds) recognition. The fluorescence intensity of DBC-Zn varies linearly with the concentration of Cr (VI) in the range of 0.1-1 µM. The detection limit of Cr2 O7 2- by DBC-Zn is 2.3 nM, which is far lower than the national safe drinking water standard stipulated by the U.S. Environmental Protection Agency (1.9 µM). The quenching mechanism of the probe can be attributed to the interaction of dynamic quenching effect (DQE) and fluorescence internal filtration effect (IFE). In addition, the probe has good stability in neutral and alkaline environment, and the accuracy of quantitative analysis of Cr2 O7 2- in lake water or tap water is more than 80%. The test paper based on DBC-Zn can effectively detect Cr2 O7 2- at the concentration of 100 ppb. It shows that the probe has a certain practical application value.

4.
Nucleic Acids Res ; 49(17): 9648-9664, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34469513

RESUMO

Retinal development is tightly regulated to ensure the generation of appropriate cell types and the assembly of functional neuronal circuitry. Despite remarkable advances have been made in understanding regulation of gene expression during retinal development, how translational regulation guides retinogenesis is less understood. Here, we conduct a comprehensive translatome and transcriptome survey to the mouse retinogenesis from the embryonic to the adult stages. We discover thousands of genes that have dynamic changes at the translational level and pervasive translational regulation in a developmental stage-specific manner with specific biological functions. We further identify genes whose translational efficiencies are frequently controlled by changing usage in upstream open reading frame during retinal development. These genes are enriched for biological functions highly important to neurons, such as neuron projection organization and microtubule-based protein transport. Surprisingly, we discover hundreds of previously uncharacterized micropeptides, translated from putative long non-coding RNAs and circular RNAs. We validate their protein products in vitro and in vivo and demonstrate their potentials in regulating retinal development. Together, our study presents a rich and complex landscape of translational regulation and provides novel insights into their roles during retinogenesis.

5.
Nat Plants ; 7(9): 1164-1165, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34518668
6.
Nutrition ; 93: 111425, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34481288

RESUMO

OBJECTIVES: Youngsters who are overweight or obese (YOO) have become an important global health concern. Some micronutrients may be modifiable influential factors. This study aimed to investigate the individual and joint association of whole-blood magnesium (WBMg) and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) in YOO. METHODS: This is a propensity score matching-based case-control study. YOO was defined depending on age- and sex-specific body mass index z-score, calculated with SAS macros (%group_standard and %WHO2007) from the World Health Organization website. WBMg, blood lipids, and covariates were carefully measured by trained technicians using a whole-blood, five-element, basic analyzer and atomic absorption spectrometer or automatic biochemical analyzer. Locally weighted scattered plot smoothing and multivariable conditional logistic regression models were applied to estimate the associations of WBMg and blood lipids in YOO. RESULTS: WBMg was positively associated with YOO. The adjusted likelihood of YOO significantly increased by 21% (odds ratio: 1.21; 95% confidence interval [CI], 1.10-1.33) with per-interquartile range elevation of WBMg. Compared with the 1st quartile, adjusted odds ratios among youngsters in the 2nd, 3rd, and 4th quartiles of WBMg were 1.11 (95% CI, 0.92-1.35), 1.29 (95% CI, 1.06-1.57), and 1.47 (95% CI, 1.18-1.83), respectively. Furthermore, the relationship between WBMg and YOO was moderated by lipid profiles. Compared with those having lower (< median) WBMg and TC, TG, LDL-C, or higher (≥ median) HDL-C, youngsters with both higher WBMg and TC, TG, LDL-C, or lower HDL-C had higher YOO odds, which averagely increased by 188%, 250%, 339%, and 369%, respectively. CONCLUSIONS: WBMg was an independent risk factor of YOO, and the associations were stronger among those with unhealthy blood lipids. Our findings can help to guide clinical and public health policies on the relevance of magnesium nutritional status.

7.
Nucleic Acids Res ; 49(18): 10717-10734, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34500466

RESUMO

The final 3'-terminal residue of the telomeric DNA G-overhang is inherently less precise. Here, we describe how alteration of the last 3'-terminal base affects the mutual recognition between two different G-rich oligomers of human telomeric DNA in the formation of heteromolecular G-quadruplexes (hetero-GQs). Associations between three- and single-repeat fragments of human telomeric DNA, target d(GGGTTAGGGTTAGGG) and probe d(TAGGGT), in Na+ solution yield two coexisting forms of (3 + 1) hybrid hetero-GQs: the kinetically favourable LLP-form (left loop progression) and the thermodynamically controlled RLP-form (right loop progression). However, only the adoption of a single LLP-form has been previously reported between the same probe d(TAGGGT) and a target variant d(GGGTTAGGGTTAGGGT) having one extra 3'-end thymine. Moreover, the flanking base alterations of short G-rich probe variants also significantly affect the loop progressions of hetero-GQs. Although seemingly two pseudo-mirror counter partners, the RLP-form exhibits a preference over the LLP-form to be recognized by a low equivalent of fluorescence dye thioflavin T (ThT). To a greater extent, ThT preferentially binds to RLP hetero-GQ than with the corresponding telomeric DNA duplex context or several other representative unimolecular GQs.

8.
Int J Mol Sci ; 22(17)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34502234

RESUMO

The WOX family is a group of plant-specific transcription factors which regulate plant growth and development, cell division and differentiation. From the available genome sequence databases of nine Triticeae species, 199 putative WOX genes were identified. Most of the identified WOX genes were distributed on the chromosomes of homeologous groups 1 to 5 and originated via the orthologous evolution approach. Parts of WOX genes in Triticum aestivum were confirmed by the specific PCR markers using a set of Triticum. durum-T. aestivum genome D substitution lines. All of these identified WOX proteins could be grouped into three clades, similar to those in rice and Arabidopsis. WOX family members were conserved among these Triticeae plants; all of them contained the HOX DNA-binding homeodomain, and WUS clade members contained the characteristic WUS-box motif, while only WUS and WOX9 contained the EAR motif. The RNA-seq and qPCR analysis revealed that the TaWOX genes had tissue-specific expression feature. From the expression patterns of TaWOX genes during immature embryo callus production, TaWOX9 is likely closely related with the regulation of regeneration process in T. aestivum. The findings in this study could provide a basis for evolution and functional investigation and practical application of the WOX family genes in Triticeae species.

9.
Front Cell Infect Microbiol ; 11: 704919, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504807

RESUMO

Aims: Long non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis (FM), remain unclear. Methods: FM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7. Results: First, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF. Conclusion: Expression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.

10.
Scand J Gastroenterol ; : 1-7, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487462

RESUMO

BACKGROUND AND AIMS: Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease (IBD). We identify an antigen-like substance called Crohn's disease (CD) antibody binding polypeptide (CABP). As a serological marker, anti-CABP may contribute to the diagnosis of IBD. The present study aims to evaluate the clinical role of anti-CABP as a serological antibody for IBD. METHODS: Using enzyme-linked immunosorbent assay (ELISA), serum anti-CABP, anti-Saccharomyces cerevisiae antibody (ASCA) and perinuclear anti-neutrophil cytoplasmic antibody (pANCA), titers were tested in 168 CD patients, 123 ulcerative colitis (UC) patients and 170 controls. The correlation between serum antibody and clinical characteristics was investigated. The diagnostic potential of the anti-CABP was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: The titers of anti-CABP (IgA or IgG) and ASCA IgG of CD patients were significantly higher than non-CD group (all p < .01). In the differential diagnosis of CD and non-CD, anti-CABP IgA revealed an area under the curve (AUC) of 0.706 and anti-CABP IgG demonstrated an AUC of 0.788. As an individual antibody, anti-CABP could effectively distinguish CD from non-CD (AUC 0.816), and the diagnostic efficacy was better than that of ASCA (AUC 0.680). The combined use of anti-CABP, ASCA and pANCA significantly improved the diagnostic value (AUC 0.857). Anti-CABP positive rates were associated with perianal lesions and disease location in CD patients (both p < .05). CONCLUSIONS: Our results suggested that anti-CABP could be used as a serological marker to assist the diagnosis of CD. CLINICAL TRIAL REGISTRATION: This trial is registered with clinical trial registration unique identifier ChiCTR2000037094.

11.
Anesth Analg ; 133(3): 781-793, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34403389

RESUMO

BACKGROUND: Orexin, a neuropeptide derived from the perifornical area of the hypothalamus (PeFLH), promotes the recovery of propofol, isoflurane, and sevoflurane anesthesias, without influencing the induction time. However, whether the orexinergic system also plays a similar role in desflurane anesthesia, which is widely applied in clinical practice owing to its most rapid onset and offset time among all volatile anesthetics, has not yet been studied. In the present study, we explored the effect of the orexinergic system on the consciousness state induced by desflurane anesthesia. METHODS: The c-Fos staining was used to observe the activity changes of orexinergic neurons in the PeFLH and their efferent projection regions under desflurane anesthesia. Chemogenetic and optogenetic techniques were applied to compare the effect of PeFLH orexinergic neurons on the induction, emergence, and maintenance states between desflurane and isoflurane anesthesias. Orexinergic terminals in the paraventricular thalamic nucleus (PVT) were manipulated with pharmacologic, chemogenetic, and optogenetic techniques to assess the effect of orexinergic circuitry on desflurane anesthesia. RESULTS: Desflurane anesthesia inhibited the activity of orexinergic neurons in the PeFLH, as well as the neuronal activity in PVT, basal forebrain, dorsal raphe nucleus, and ventral tegmental area, as demonstrated by c-Fos staining. Activation of PeFLH orexinergic neurons prolonged the induction time and accelerated emergence from desflurane anesthesia but only influenced the emergence in isoflurane anesthesia, as demonstrated by chemogenetic and pharmacologic techniques. Meanwhile, optical activation of orexinergic neurons exhibited a long-lasting inhibitory effect on burst-suppression ratio (BSR) under desflurane anesthesia, and the effect may be contributed by the orexinergic PeFLH-PVT circuitry. The orexin-2 receptor (OX2R), but not orexin-1 receptor (OX1R), in the PVT, which had been inhibited most significantly by desflurane, mediated the proemergence effect of desflurane anesthesia. CONCLUSIONS: We discovered, for the first time, that orexinergic neurons in the PeFLH could not only influence the maintenance and emergence from isoflurane and desflurane anesthesias but also affect the induction under desflurane anesthesia. Furthermore, this specific effect is probably mediated by orexinergic PeFLH-PVT circuitry, especially OX2Rs in the PVT.


Assuntos
Período de Recuperação da Anestesia , Anestesia por Inalação , Anestésicos Inalatórios/farmacologia , Estado de Consciência/efeitos dos fármacos , Desflurano/farmacologia , Isoflurano/farmacologia , Núcleos da Linha Média do Tálamo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Orexinas/farmacologia , Potenciais de Ação , Animais , Eletroencefalografia , Masculino , Núcleos da Linha Média do Tálamo/metabolismo , Neurônios/metabolismo , Optogenética , Receptores de Orexina/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Sprague-Dawley , Fatores de Tempo
12.
Aging (Albany NY) ; 13(16): 20511-20533, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34432649

RESUMO

Interferon (IFN) signaling pathways play crucial roles in the pathogenesis of rheumatoid arthritis (RA). Prior studies have mainly studied mixed alterations in the IFN signaling pathway in RA, but these studies have not been sufficient to elucidate how imbalanced IFN signaling subtly influences immune cells. Single-cell RNA (scRNA) sequencing makes it possible to better understand the alternations in the interferon signaling pathways in RA. In the present study, we found that IFN signaling pathways were activated in natural killer (NK) cells, monocytes, T cells, B cells, and most immune cell subclasses in RA. We then explored and analyzed the connections between abnormal IFN signaling pathways and cellular functional changes in RA. Single-Cell rEgulatory Network Inference and Clustering (SCENIC) analysis and gene regulatory network (GRN) construction were also performed to identify key transcription factors in RA. Finally, we also investigated altered IFN signaling pathways in multiple RA peripheral blood samples, which indicated that abnormal IFN signaling pathways were universally observed in RA. Our study contributes to a better understanding of the delicate and precise regulation of IFN signaling in the immune system in RA. Furthermore, common alternations in IFN signaling pathway-related transcription factors could help to identify novel therapeutic targets for RA treatment.

13.
Sci Adv ; 7(32)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34362731

RESUMO

Altered mitochondrial quality control and dynamics may contribute to neurodegenerative diseases, including Parkinson's disease, but we understand little about these processes in neurons. We combined time-lapse microscopy and correlative light and electron microscopy to track individual mitochondria in neurons lacking the fission-promoting protein dynamin-related protein 1 (Drp1) and delineate the kinetics of PINK1-dependent pathways of mitochondrial quality control. Depolarized mitochondria recruit Parkin to the outer mitochondrial membrane, triggering autophagosome formation, rapid lysosomal fusion, and Parkin redistribution. Unexpectedly, these mitolysosomes are dynamic and persist for hours. Some are engulfed by healthy mitochondria, and others are deacidified before bursting. In other cases, Parkin is directly recruited to the matrix of polarized mitochondria. Loss of PINK1 blocks Parkin recruitment, causes LC3 accumulation within mitochondria, and exacerbates Drp1KO toxicity to dopamine neurons. These results define a distinct neuronal mitochondrial life cycle, revealing potential mechanisms of mitochondrial recycling and signaling relevant to neurodegeneration.

14.
Dev Cell ; 56(16): 2313-2328.e7, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34428398

RESUMO

How autophagy initiation is regulated and what the functional significance of this regulation is are unknown. Here, we characterized the role of yeast Vac8 in autophagy initiation through recruitment of PIK3C3-C1 to the phagophore assembly site (PAS). This recruitment is dependent on the palmitoylation of Vac8 and on its middle ARM domains for binding PIK3C3-C1. Vac8-mediated anchoring of PIK3C3-C1 promotes PtdIns3P generation at the PAS and recruitment of the PtdIns3P binding protein Atg18-Atg2. The mouse homolog of Vac8, ARMC3, is conserved and functions in autophagy in mouse testes. Mice lacking ARMC3 have normal viability but show complete male infertility. Proteomic analysis indicated that the autophagic degradation of cytosolic ribosomes was blocked in ARMC3-deficient spermatids, which caused low energy levels of mitochondria and motionless flagella. These studies uncovered a function of Vac8/ARMC3 in PtdIns3-kinase anchoring at the PAS and its physical significance in mammalian spermatogenesis with a germ tissue-specific autophagic function.

15.
Cell Death Dis ; 12(7): 703, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262024

RESUMO

Lysine crotonylation has been discovered in histone and non-histone proteins and found to be involved in diverse diseases and biological processes, such as neuropsychiatric disease, carcinogenesis, spermatogenesis, tissue injury, and inflammation. The unique carbon-carbon π-bond structure indicates that lysine crotonylation may use distinct regulatory mechanisms from the widely studied other types of lysine acylation. In this review, we discussed the regulation of lysine crotonylation by enzymatic and non-enzymatic mechanisms, the recognition of substrate proteins, the physiological functions of lysine crotonylation and its cross-talk with other types of modification. The tools and methods for prediction and detection of lysine crotonylation were also described.


Assuntos
Processamento de Proteína Pós-Traducional , Proteínas/metabolismo , Acilação , Animais , Humanos , Lisina , Lisina Acetiltransferases/metabolismo , Conformação Proteica , Relação Estrutura-Atividade , Especificidade por Substrato
16.
Talanta ; 233: 122533, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215036

RESUMO

The formation of G-quadruplex (G4) structures in oncogenic G-rich promoter regions are implicated in their biological functions, especially the inhibition of transcription. The binding of cations is thought to contribute to the stabilization of the G4 formation and competition against the duplex formation in the genomic sequence. Furthermore, it might affect the recognition of DNA-binding proteins. Therefore, measuring the interaction between G4 DNA and cations in a free solution environment is critical for evaluating G4 DNA biological functions. However, how binding to cations (K+ and NH4+) affects the folding equilibrium of the G4 structure remains unclear. In this work, a Taylor dispersion analysis (TDA) method using a capillary electrophoresis (CE) instrument was established for the quantitative characterization of the cation-dependent G4 formation in the human c-KIT oncogene promoter region, as well as diffusivities and hydrodynamic radii of DNA variations before and after folding. Our results showed that both K+ and NH4+ can induce the random-coiled c-KIT DNA to unfold and form a more unstretched intermediate state and then fold into tightly structured G4s with smaller size. The G4 size induced by NH4+ was smaller than that induced by K+ ions, though these two cations induced the c-KIT G4 DNA formation with similar binding constants (order of magnitude around 106 M-1). The TDA method can be widely used for rapid structural analyses of trace amounts of DNA mixtures, which effectively differentiate DNA variations or DNA-ligand complex conformations.


Assuntos
Quadruplex G , Oncogenes , DNA/genética , Humanos , Ligantes , Regiões Promotoras Genéticas
17.
J Am Chem Soc ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196527

RESUMO

The simultaneous control of the defect species and surface properties of semiconducting materials is a crucial aspect of improving photocatalytic performance, yet it remains challenging. Here, we synthesized Mg-Zr-codoped single-crystalline Ta3N5 (Ta3N5:Mg+Zr) nanoparticles by a brief NH3 nitridation process, exhibiting photocatalytic water reduction activity 45 times greater than that of pristine Ta3N5 under visible light. A coherent picture of the relations between the defect species (comprising reduced Ta, nitrogen vacancies and oxygen impurities), surface properties (associated with dispersion of the Pt cocatalyst), charge carrier dynamics, and photocatalytic activities was drawn. The tuning of defects and simultaneous optimization of surface properties resulting from the codoping evidently resulted in the generation of high concentrations of long-lived electrons in this material as well as the efficient migration of these electrons to evenly distributed surface Pt sites. These effects greatly enhanced the photocatalytic activity. This work highlights the importance and feasibility of improving multiple properties of a catalytic material via a one-step strategy.

18.
Adv Exp Med Biol ; 1208: 357-371, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34260033

RESUMO

Autophagy is an important intracellular lysosomal degradation process in cells, which is highly conserved from yeast to mammals. The process of autophagy is roughly divided into the following key steps: the formation of a membrane structure called ISM (isolated membrane) after stimulation, the biogenesis and maturation of autophagosomes, and finally the degradation of autophagosomes. A number of proteins are required to function in the whole process of autophagy. Since the initial genetic screening in yeast cells, multiple genes that play pivotal roles in autophagy have been discovered. These molecules have been named ATG genes (AuTophaGy related genes). The screening for new key molecules involved in autophagy has greatly promoted the characterization of the mechanism of the autophagy machinery and provides multiple targets for the development of autophagy-based regulatory drugs.


Assuntos
Autofagossomos , Autofagia , Animais , Autofagia/genética , Proteínas Relacionadas à Autofagia/genética , Lisossomos , Saccharomyces cerevisiae
19.
Adv Exp Med Biol ; 1208: 373-386, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34260034

RESUMO

Autophagy is an evolutionarily conserved intracellular degradation process. Autophagy is closely involved in human health and diseases. In recent years, mass spectrometry-based proteomic methods have become important and powerful tools for autophagy studies. These types of techniques have been especially helpful to reveal the range of degradation substrates of autophagy through large-scale, unbiased analysis of cellular proteomes. At present, a variety of mass spectrometry-based proteomics methods have been successfully applied to autophagy research.


Assuntos
Autofagia , Proteômica , Humanos , Espectrometria de Massas , Proteoma/genética
20.
Plant Genome ; : e20096, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34275212

RESUMO

Characterization of genomic regions underlying adaptation of landraces can reveal a quantitative genetics framework for local wheat (Triticum aestivum L.) adaptability. A collection of 512 wheat landraces from the eastern edge of the Fertile Crescent in Iran and Pakistan were genotyped using genome-wide single nucleotide polymorphism markers generated by genotyping-by-sequencing. The minor allele frequency (MAF) and the heterozygosity (H) of Pakistani wheat landraces (MAF = 0.19, H = 0.008) were slightly higher than the Iranian wheat landraces (MAF = 0.17, H = 0.005), indicating that Pakistani landraces were slightly more genetically diverse. Population structure analysis clearly separated the Pakistani landraces from Iranian landraces, which indicates two separate adaptability trajectories. The large-scale agro-climatic data of seven variables were quite dissimilar between Iran and Pakistan as revealed by the correlation coefficients. Genome-wide association study identified 91 and 58 loci using agroclimatic data, which likely underpin local adaptability of the wheat landraces from Iran and Pakistan, respectively. Selective sweep analysis identified significant hits on chromosomes 4A, 4B, 6B, 7B, 2D, and 6D, which were colocalized with the loci associated with local adaptability and with some known genes related to flowering time and grain size. This study provides insight into the genetic diversity with emphasis on the genetic architecture of loci involved in adaptation to local environments, which has breeding implications.

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