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1.
Cell Cycle ; : 1-16, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160130

RESUMO

Literatures indicate that microRNA-129-5p (miR-129-5p) or Fas-associated death domain (FADD) is related to intervertebral disc degeneration (IDD), but the effect of miR-129-5p/FADD axis on IDD is not studied. The study aimed to investigate whether miR-129-5p influenced immune privilege and nucleus pulposus (NP) cell apoptosis in rats with IDD via regulating FADD.A rat model with caudal IDD was established, and injected with miR-129-5p agomir or miR-129-5p antagomir to figure out the character of miR-129-5p in the cell apoptosis and inflammation in the nucleus pulposus (NP) tissues of IDD rats. NP cells were grouped as the same ways for determining proliferation, apoptosis, and senescence in NP cells of IDD rats. Annexin V-FITC/PI double staining detected the apoptosis of macrophages and CD8+ cells co-cultured via transfected NP cells. Expression of miR-129-5p, FADD, collagen I, collagen II, aggrecan and Sox-9 in NP tissues and cells were determined.Up-regulated miR-129-5p decreased FADD, collagen I and elevated collagen Ⅱ, aggrecan, and Sox-9 in NP tissues and repressed inflammation in serum and NP tissues in IDD rats. Up-regulated miR-129-5p facilitated proliferation, inhibited senescence, apoptosis, and decreased FADD, collagen I and increased collagen Ⅱ, aggrecan, and Sox-9 in NP cells of IDD rats. Elevated miR-129-5p promoted the apoptosis of macrophages and CD8+ cells.We pronounced that up-regulated miR-129-5p inhibited the apoptosis and facilitated the proliferation of NP cells, as well as the apoptosis of macrophages and CD8+ cells via decreased FADD in IDD, suggesting that miR-129-5p had a protective effect on IDD.

2.
J Steroid Biochem Mol Biol ; 200: 105635, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32068072

RESUMO

Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive diseases characterized by enzymatic defects in steroid synthesis. Lipoid congenital adrenal hyperplasia (LCAH) is the most severe form of CAH, insofar as the initial step of steroid synthesis is impaired. Variants in the steroid acute regulatory (STAR) gene are responsible for LCAH. To describe the clinical and genetic characteristics of three Chinese patients with LCAH. We analyzed the history, clinical manifestations, physical examination, laboratory data, and computed tomography findings of three girls with LCAH. The STAR gene of the probands and their parents were sequenced using genomic DNA. The wild-type and mutant STAR cDNAs were inserted into the pcDNA3.1(+) plasmid vector and transiently transfected into COS7 cells. The enzymatic activities of the wild-type and mutant STAR were evaluated by the enzyme-dependent conversion efficiency of cholesterol to pregnenolone. We identified the molecular genetic abnormalities in three patients with LCAH. All three patients had a female phenotype: karyotype of patients 1 and 2 was 46, XY and patient 3 was 46, XX. DNA sequencing revealed compound heterozygous variants in STAR for three probands. Two variants, c.659A > G/p.His220Arg and exon 2-3 deletion, were novel. In vitro functional studies uncovered that the His220Arg variant retained 19.2 % of enzymatic activity compared to that of the wild type.

3.
Biomed Res Int ; 2020: 1953242, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32051823

RESUMO

Brucella-caused brucellosis is one of the most widespread worldwide zoonoses. Lipopolysaccharide (LPS) of Brucella, which functions as pathogen-associated molecular patterns (PAMPs), is an important virulence factor that elicits protective antibodies. Per of B. melitensis is involved in the biosynthesis of the O-side chain of LPS. Autophagy is a crucial element of the innate immune response against intracellular pathogens including Brucella. In this study, we observed that autophagy was inhibited in RAW264.7 cells infected with Brucella melitensis ∆per. And, a high-throughput array-based screen and qRT-PCR validation were performed to identify the differentially expressed miRNAs in RAW264.7 cells infected with B. melitensis M5-90 ∆per. The results suggested that mmu-miR-146a-5p, mmu-miR-155-5p, mmu-miR-146b-5p, and mmu-miR-3473a were upregulated and mmu-miR-30c-5p was downregulated. During B. melitensis M5-90 ∆per infection, the increased expression of miR-146b-5p inhibited the autophagy activation in RAW264.7 cells. Using a bioinformatics approach, Tbc1d14 was predicted to be a potential target of miR-146b-5p. The results of a luciferase reporter assay indicated that miR-146b-5p directly targeted the 3'-UTR of Tbc1d14, and the interaction between miR-146b-5p and the 3'-UTR of Tbc1d14 was sequence-specific. High-throughput RNA-Seq-based screening was performed to identify differentially expressed genes in Tbc1d14-expressing RAW264.7 cells, and these were validated by qRT-PCR. Among the differentially expressed genes, four autophagy associated genes, IFNγ-inducible p47 GTPase 1 (IIGP1), nuclear receptor binding protein 2 (Nrbp2), transformation related protein 53 inducible nuclear protein 1 (Trp53inp1), and immunity-related GTPase family M member 1 (Irgm1), were obtained. Our findings provide important insights into the functional mechanism of LPS of B. melitensis.

4.
Nat Commun ; 11(1): 988, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080171

RESUMO

Increasing grain yield of maize (Zea mays L.) is required to meet the rapidly expanding demands for maize-derived food, feed, and fuel. Breeders have enhanced grain productivity of maize hybrids by pyramiding desirable characteristics for larger ears. However, loci selected for improving grain productivity remain largely unclear. Here, we show that a serine/threonine protein kinase encoding gene KERNEL NUMBER PER ROW6 (KNR6) determines pistillate floret number and ear length. Overexpression of KNR6 or introgression of alleles lacking the insertions of two transposable elements in the regulatory region of KNR6 can significantly enhance grain yield. Further in vitro evidences indicate that KNR6 can interact with an Arf GTPase-activating protein (AGAP) and its phosphorylation by KNR6 may affect ear length and kernel number. This finding provides knowledge basis to enhance maize hybrids grain yield.

5.
Heart ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054669

RESUMO

OBJECTIVE: This study assessed whether apolipoprotein CIII-lipoprotein(a) complexes (ApoCIII-Lp(a)) associate with progression of calcific aortic valve stenosis (AS). METHODS: Immunostaining for ApoC-III was performed in explanted aortic valve leaflets in 68 patients with leaflet pathological grades of 1-4. Assays measuring circulating levels of ApoCIII-Lp(a) complexes were measured in 218 patients with mild-moderate AS from the AS Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial. The progression rate of AS, measured as annualised changes in peak aortic jet velocity (Vpeak), and combined rates of aortic valve replacement (AVR) and cardiac death were determined. For further confirmation of the assay data, a proteomic analysis of purified Lp(a) was performed to confirm the presence of apoC-III on Lp(a). RESULTS: Immunohistochemically detected ApoC-III was prominent in all grades of leaflet lesion severity. Significant interactions were present between ApoCIII-Lp(a) and Lp(a), oxidised phospholipids on apolipoprotein B-100 (OxPL-apoB) or on apolipoprotein (a) (OxPL-apo(a)) with annualised Vpeak (all p<0.05). After multivariable adjustment, patients in the top tertile of both apoCIII-Lp(a) and Lp(a) had significantly higher annualised Vpeak (p<0.001) and risk of AVR/cardiac death (p=0.03). Similar results were noted with OxPL-apoB and OxPL-apo(a). There was no association between autotaxin (ATX) on ApoB and ATX on Lp(a) with faster progression of AS. Proteomic analysis of purified Lp(a) showed that apoC-III was prominently present on Lp(a). CONCLUSION: ApoC-III is present on Lp(a) and in aortic valve leaflets. Elevated levels of ApoCIII-Lp(a) complexes in conjunction with Lp(a), OxPL-apoB or OxPL-apo(a) identify patients with pre-existing mild-moderate AS who display rapid progression of AS and higher rates of AVR/cardiac death. TRIAL REGISTRATION: NCT00800800.

6.
Sci Rep ; 10(1): 1677, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015470

RESUMO

Plant seed germination is a crucial developmental event that has significant effects on seedling establishment and yield production. This process is controlled by multiple intrinsic signals, particularly phytohormones. The gaseous hormone ethylene stimulates seed germination; however, the genetic basis of ethylene production in maize during seed germination remains poorly understood. In this study, we quantified the diversity of germination among 14 inbred lines representing the parental materials corresponding to multiple recombinant inbred line (RIL) mapping populations. Quantitative trait loci (QTLs) controlling ethylene production were then identified in germinating seeds from an RIL population constructed from two parental lines showing differences in both germination speed and ethylene production during germination. To explore the possible genetic correlations of ethylene production with other traits, seed germination and seed weight were evaluated using the same batch of samples. On the basis of high-density single nucleotide polymorphism-based genetic linkage maps, we detected three QTLs for ethylene production in germinating seeds, three QTLs for seed germination, and four QTLs for seed weight, with each QTL explaining 5.8%-13.2% of the phenotypic variation of the trait. No QTLs were observed to be co-localized, suggesting that the genetic bases underlying the three traits are largely different. Our findings reveal three chromosomal regions responsible for ethylene production during seed germination, and provide a valuable reference for the future investigation of the genetic mechanism underlying the role of the stress hormone ethylene in maize germination control under unfavourable external conditions.

8.
Neuropsychologia ; 140: 107383, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32057933

RESUMO

During comprehension, language users not only immediately integrate information from local sentence context, but also information from global discourse context for full understanding. In the present study, we examined whether the time course of these integration processes is constrained by language users' working memory capacity. Sentence and discourse stimuli were constructed. For the sentence stimuli, each sentence contained a critical word that was either congruent or incongruent with its preceding sentence context. For the discourse stimuli, each discourse contained four sentences with a target word embedded at the final sentence and the target word was either congruent or incongruent with the information provided at the first sentence of the discourse. Participants of high and low working memory span were instructed to read for comprehension. Our results showed that while the high span readers showed the N400 and P600 effects to semantically incongruent words, the low span readers only showed the P600 effect. This pattern was found regardless of whether the incongruent words were placed at sentence or discourse context. These results suggest that the low span readers are relatively delayed than the high span ones at both sentence- and discourse-level semantic integration and indicate that working memory functions have greater influence than context scope on the time course of semantic integration.

9.
Aging (Albany NY) ; 12(2): 1577-1590, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980592

RESUMO

Nearly half of metastatic breast cancers (MBC) have genetic aberrations in the PI3K/AKT pathway. To investigate the distinct effect of these aberrations on MBC, 193 MBC patients who progressed after the early line (≤2) salvage treatment voluntarily received next generation sequencing (NGS) for a panel of 1,021 genes. 93 (48%) patients had genetic aberrations in the PI3K/AKT pathway. The number of patients with PIK3CA mutations in kinase domain (KD), helical domain (HD) and other domain (OD), were 36 (18.7%), 26 (13.5%), 10 (5.2%), respectively. 21 (10.9%) patients had mutations in PI3K/AKT pathway genes other than PIK3CA (P/A). Compared to PI3K/AKT-wild type (WT) patients, PIK3CA-HD patients had a significantly shorter progression-free survival (PFS) (Logrank p-value < 0.0001). PIK3CA-KD, PIK3CA-OD and other P/A mutations showed similar PFS to WT patients (Logrank p-value = 0.63). PIK3CA-HD patients had a distinct ctDNA mutation profile to patients with other PI3K/AKT mutations. PIK3CA-HD patients had a higher rate of FGFR and NF1 aberrations. In addition, more PIK3CA-HD carriers were TMB-high. Cox regression analyses suggested that PIK3CA-HD mutations, FGFR aberrations and high TMB were all significant risk factors for poor PFS. In conclusion, future research needs to focus more on the treatment strategies targeting PIK3CA-HD mutations.

10.
Viruses ; 12(1)2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31963559

RESUMO

Orf is a zoonotic disease that has caused huge economic losses globally. Systematical analysis of dysregulated cellular micro RNAs (miRNAs) in response to Orf virus (ORFV) infection has not been reported. In the current study, miRNA sequencing and RNA sequencing (RNA-seq) were performed in goat skin fibroblast (GSF) cells at 0, 18, and 30 h post infection (h.p.i). We identified 140 and 221 differentially expressed (DE) miRNAs at 18 and 30 h.p.i, respectively. We also identified 729 and 3961 DE genes (DEGs) at 18 and 30 h.p.i, respectively. GO enrichment analysis indicates enrichment of apoptotic regulation, defense response to virus, immune response, and inflammatory response at both time points. DE miRNAs and DEGs with reverse expression were used to construct miRNA-gene networks. Seven DE miRNAs and seven DEGs related to "negative regulation of viral genome replication" were identified. These were validated by RT-qPCR. Cfa-let-7a, a significantly upregulated miRNA, was found to repress Thrombospondin 1 (THBS1) mRNA and protein expression by directly targeting the THBS1 3' untranslated region. THBS1 has been reported to induce apoptosis; therefore, the cfa-let-7a-THBS1 axis may play an important role in cellular apoptosis during ORFV infection. This study provides new insights into ORFV and host cell interaction mechanisms.

11.
Nanotechnology ; 31(22): 225202, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952068

RESUMO

Dynamically regulated coherent light emission offers a significant impact on improving white light generation, optical communication, on-chip photonic integration, and sensing. Here, we have demonstrated two mechanisms of strain-induced dynamic regulation of ZnO lasing modes through an individual ZnO microbelt and microrod prepared by vapor-phase transport method. We systematically explained the dependence on externally applied strain and crystal orientation. Compared with the reduced size of resonant cavity played a major role in the microbelt, the resonant wavelength variation of the microrod under tensile stress is affected by the change in both the cavity size and the refractive index, which tends to antagonize in the direction of movement. It shows that the refractive index can be effectively regulated only when the stress is in the same direction along the c-axis. The results on the linear relationship between the resonance wavelength variation and applied strain imply the capacity of the devices to detect tiny stresses due to the ultra-narrow line width of the cavity mode with a high-quality factor of âˆ¼104. It not only has a positive influence in the field of the modulated coherent light source, but also provides a feasible strategy for implementing color-resolved non-contact strain sensors.

12.
Molecules ; 25(2)2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31963730

RESUMO

In this article, we report the design, synthesis, photodynamic properties, and in vitro evaluation of photoactivatable prodrug for the poly (ADP-ribose) polymerase 1 (PARP-1) inhibitor Talazoparib. In order to yield a photoactivatable, inactive prodrug, photoactivatable protecting groups (PPGs) were employed to mask the key pharmacophore of Talazoparib. Our study confirmed the good stability and photolytic effect of prodrugs. A PARP-1 enzyme inhibition assay and PARylation experiment showed that the inhibitory activity of the prodrug was reduced 380 times and more than 658 times, respectively, which proved that the prodrug's expected activity was lost after PPG protection. In BRCA1- and BRCA2-deficient cell lines, the inhibitory activity of the compound was significantly restored after ultraviolet (UV) irradiation. The results indicate that the photoactivatable prodrug strategy is an interesting approach for studying PARP inhibitors. Meanwhile, the described photoactivatable prodrug also provided a new biological tool for the mechanism research of PARP.

13.
J Pediatr Endocrinol Metab ; 33(2): 265-270, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31953997

RESUMO

Background The relationship between cytokines and lipid metabolism has garnered attention given their potential metabolic interaction. However, the relationship between adropin and lipopolysaccharide-binding protein (LBP) and obesity-related inflammation has not been reported, as well as their relationship with serum lipid profiles. Objective This study analyzed the association of serum adropin, leptin, LBP levels and lipid profiles in obese children ranging from 5 to 14 years old. Methods Plasma lipid measurements included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) by standard methods, and serum adropin, leptin and LBP levels was measured by enzyme-linked immunosorbent assay (ELISA). Results One hundred and twenty-four children (9.25 ± 1.59 years) with obesity and 42 controls (8.81 ± 1.94 years) were assessed. Compared with the control group, the serum adropin concentrations in the obesity group were significantly lower, whereas the serum leptin and LBP levels were significantly higher. Pearson's correlation analysis showed that serum adropin levels negatively correlated with TG, waist to hip ratio (WHR) and body mass index (BMI), and positively correlated with HDL-c. Serum LBP levels positively correlated with LDL-c and WHR. After adjusting for LBP, the correlation coefficients of adropin with TG, HDL-c and leptin were more robust. Also, after adjusting for serum LBP, the correlation coefficient of leptin with TG was attenuated, yet remained statistically significant, and the correlation coefficient of leptin with HDL-c was enhanced. Conclusions Children with obesity have decreased serum adropin levels and elevated leptin and LBP levels. Each of the three serum cytokines were associated with lipid metabolism, and this association warrants further study.

14.
Bioorg Chem ; 95: 103556, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31927317

RESUMO

STING (Stimulator of Interferon Genes) has become a focal point in immunology research and a target in drug discovery. The discovery of a potent human-STING agonist is expected to revolutionize current anti-virus or cancer immunotherapy. Inspired by the structure and function of murine STING-specific agonists (DMXAA and CMA), we rationally designed and synthesized four series of novel compounds for the enhancement of human sensitivity. In the cell-based assay, we identified six compounds from all the synthetic small molecules: 2g, 9g, and 12b are STING agonists that are efficacious across species, and all have the skeleton of acridone; 1b, 1c, and 12c just function in the murine STING pathway. Notably, 12b exhibits the best activity among the six agonists, and its inductions of both human and murine STING-dependent signalling are similar to that of 2'3'-cGAMP, which is a well-known STING inducer. While a protein assay indicated that 2 g, 9 g, and 12b could activate the pathway by directly binding human STING, 12b also displayed the strongest binding affinity. Additionally, our studies show that 12b can induce faster, more powerful, and more durable responses of assorted cytokines in a native system than 2'3'-cGAMP. Consequently, our team is the first to successfully modify murine STING agonists to obtain human sensitivity, and these results suggest that 12b is a potent direct-human-STING agonist. Additionally, the acridone analogues demonstrate tremendous potential in the treatment of tumours or viral infections.

15.
Nat Commun ; 11(1): 186, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924762

RESUMO

Sodium (Na+) toxicity is one of the major damages imposed on crops by saline-alkaline stress. Here we show that natural maize inbred lines display substantial variations in shoot Na+ contents and saline-alkaline (NaHCO3) tolerance, and reveal that ZmNSA1 (Na+ Content under Saline-Alkaline Condition) confers shoot Na+ variations under NaHCO3 condition by a genome-wide association study. Lacking of ZmNSA1 promotes shoot Na+ homeostasis by increasing root Na+ efflux. A naturally occurred 4-bp deletion decreases the translation efficiency of ZmNSA1 mRNA, thus promotes Na+ homeostasis. We further show that, under saline-alkaline condition, Ca2+ binds to the EF-hand domain of ZmNSA1 then triggers its degradation via 26S proteasome, which in turn increases the transcripts levels of PM-H+-ATPases (MHA2 and MHA4), and consequently enhances SOS1 Na+/H+ antiporter-mediated root Na+ efflux. Our studies reveal the mechanism of Ca2+-triggered saline-alkaline tolerance and provide an important gene target for breeding saline-alkaline tolerant maize varieties.

16.
Cell Metab ; 31(1): 189-206.e8, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31761566

RESUMO

Oxidized phospholipids (OxPLs), which arise due to oxidative stress, are proinflammatory and proatherogenic, but their roles in non-alcoholic steatohepatitis (NASH) are unknown. Here, we show that OxPLs accumulate in human and mouse NASH. Using a transgenic mouse that expresses a functional single-chain variable fragment of E06, a natural antibody that neutralizes OxPLs, we demonstrate the causal role of OxPLs in NASH. Targeting OxPLs in hyperlipidemic Ldlr-/- mice improved multiple aspects of NASH, including steatosis, inflammation, fibrosis, hepatocyte death, and progression to hepatocellular carcinoma. Mechanistically, we found that OxPLs promote ROS accumulation to induce mitochondrial dysfunction in hepatocytes. Neutralizing OxPLs in AMLN-diet-fed Ldlr-/- mice reduced oxidative stress, improved hepatic and adipose-tissue mitochondrial function, and fatty-acid oxidation. These results suggest targeting OxPLs may be an effective therapeutic strategy for NASH.

17.
Plant J ; 101(2): 278-292, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31529523

RESUMO

The nutritional traits of maize kernels are important for human and animal nutrition, and these traits have undergone selection to meet the diverse nutritional needs of humans. However, our knowledge of the genetic basis of selecting for kernel nutritional traits is limited. Here, we identified both single and epistatic quantitative trait loci (QTLs) that contributed to the differences of oil and carotenoid traits between maize and teosinte. Over half of teosinte alleles of single QTLs increased the values of the detected oil and carotenoid traits. Based on the pleiotropism or linkage information of the identified single QTLs, we constructed a trait-locus network to help clarify the genetic basis of correlations among oil and carotenoid traits. Furthermore, the selection features and evolutionary trajectories of the genes or loci underlying variations in oil and carotenoid traits revealed that these nutritional traits produced diverse selection events during maize domestication and improvement. To illustrate more, a mutator distance-relative transposable element (TE) in intron 1 of DXS2, which encoded a rate-limiting enzyme in the methylerythritol phosphate pathway, was identified to increase carotenoid biosynthesis by enhancing DXS2 expression. This TE occurs in the grass teosinte, and has been found to have undergone selection during maize domestication and improvement, and is almost fixed in yellow maize. Our findings not only provide important insights into evolutionary changes in nutritional traits, but also highlight the feasibility of reintroducing back into commercial agricultural germplasm those nutritionally important genes hidden in wild relatives.

18.
J Autoimmun ; 106: 102349, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31629629

RESUMO

BACKGROUND: Genome-wide association studies have identified over 120 risk loci for psoriasis. However, most of the variations are located in non-coding region with high frequency and small effect size. Pathogenetic variants are rarely reported except HLA-C*0602 with the odds ratio being approximately 4.0 in Chinese population. Although rare variations still account for a small proportion of phenotypic variances in complex diseases, their effect on phenotypes is large. Recently, more and more studies focus on the low-frequency functional variants and have achieved a certain amount of success. METHOD: Whole genome sequencing and sanger sequencing was performed on 8 MZ twin pairs discordant for psoriasis to scan and verified the de novo mutations (DNMs). Additionally, 665 individuals with about 20 years' medical history versus 2054 healthy controls and two published large population studies which had about 8 years' medical history (including 10,727 cases versus 10,582 controls) were applied to validate the enrichment of rare damaging mutations in two DNMs genes. Besides, to verify the pathogenicity of candidate DNM in C3, RNA-sequencing for CD4+, CD8+ T cells of twins and lesion, non-lesion skin of psoriasis patients were carried out. Meanwhile, the enzyme-linked immunosorbent assay kit was used to detect the level of C3, C3b in the supernatant of peripheral blood. RESULT: A total of 27 DNMs between co-twins were identified. We found six of eight twins carry HLA-C∗0602 allele which have large effects on psoriasis. And it is interesting that a missense mutation in SPRED1 and a splice region mutation in C3 are found in the psoriasis individuals in the other two MZ twin pairs without carrying HLA-C*0602 allele. In the replication stage, we found 2 loss-of-function (LOF) variants of C3 only in 665 cases with about 20 years' medical history and gene-wise analysis in 665 cases and 2054 controls showed that the rare missense mutations in C3 were enriched in cases (OR = 1.91, P = 0.0028). We further scanned the LOF mutations of C3 in two published studies (about 8 years' medical history), and found one LOF mutation in the case without carrying HLA-C*0602. In the individual with DNM in C3, RNA sequencing showed the expression level of C3 in skin was significant higher than healthy samples in public database (TPM fold change = 1.40, P = 0.000181) and ELISA showed protein C3 in peripheral blood was higher (~2.2-fold difference) than the other samples of twins without DNM in C3. CONCLUSION: To the best of our knowledge, this is the first report that DNM in C3 is the likely pathological mutations, and it provided a better understanding of the genetic etiology of psoriasis and additional treatments for this disease.

19.
Plant Physiol Biochem ; 146: 133-142, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31751913

RESUMO

Avena sativa L. is the most important cultivated oat species worldwide. Although photoperiod-insensitive oat varieties exist, the molecular mechanisms underlying their photoperiod sensitivity are poorly understood. This study investigated the effects of day length on the fioral transition of oats and the mechanisms underlying oat photoperiod insensitivity. Photoperiod-sensitive and photoperiod-insensitive varieties, including gp012, were used in shading experiments, and the developing leaves and main shoot apices (MSAs) of the HONGQI2 and gp012 varieties were used for sequencing. Leaves and MSAs were collected in 2016, and their transcriptomes were sequenced. The photoperiod-insensitive varieties headed under both short-day and long-day conditions, while the photoperiod-sensitive varieties headed only under long-day conditions. A total of 60673 transcript sequences were obtained, 7932 of which were differentially expressed; 3194 and 4738 transcripts were differentially expressed in the leaves and MSAs, respectively. A total of 25793 transcripts were classified into 123 pathways based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The carbon metabolism pathways were dominant, followed by ribosome and protein processing in the endoplasmic reticulum. In addition, 203 transcripts were classified into the circadian rhythm pathway. Compared with the expression of pseudo-response regulator protein 37 (PRR37) in photoperiod-sensitive varieties, that in photoperiod-insensitive varieties was upregulated. Among the differentially expressed transcripts (DETs), 8 MADS-box genes were identified. PRR37 is a key regulator of oat photoperiod insensitivity. The obtained transcriptome dataset may provide a reference for analyzing oat transcript expression, and the results should be used as a reference for oat breeding and production.

20.
Chemosphere ; 244: 125485, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31809929

RESUMO

Microplastics are widespread emerging marine pollutants that have been found in the coral reef ecosystem. In the present study, using Cladocopium goreaui as a symbiont representative, we investigated cytological, physiological, and molecular responses of a Symbiodiniaceae species to weeklong microplastic exposure (Polystyrene, diameter 1.0 µm, 9.0 × 109 particles L-1). The density and size of algal cells decreased significantly at 7 d and 6-7 d of microplastic exposure, respectively. Chlorophyll a content increased significantly at 7 d of exposure, whereas Fv/Fm did not change significantly during the entire exposure period. We observed significant increases in superoxide dismutase activity and caspase3 activation level, significant decrease in glutathione S-transferase activity, but no change in catalase activity during the whole exposure period. Transcriptomic analysis revealed 191 significantly upregulated and 71 significantly downregulated genes at 7 d after microplastic exposure. Fifteen GO terms were overrepresented for these significantly upregulated genes, which were grouped into four categories including transmembrane ion transport, substrate-specific transmembrane transporter activity, calcium ion binding, and calcium-dependent cysteine-type endopeptidase activity. Thirteen of the significantly upregulated genes encode metal ion transporter and ammonium transporter, and five light-harvesting protein genes were among the significantly downregulated genes. These results demonstrate that microplastics can act as an exogenous stressor, suppress detoxification activity, nutrient uptake, and photosynthesis, elevate oxidative stress, and raise the apoptosis level through upregulating ion transport and apoptotic enzymes to repress the growth of C. goreaui. These effects have implications in negative impacts of microplastics on coral-Symbiodiniaceae symbiosis that involves C. goreaui.

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