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1.
J Proteomics ; 210: 103527, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31610263

RESUMO

Bombyx mori nucleopolyhedrovirus (BmNPV) is a major pathogen causing severe economic loss. Previous studies have revealed that some proteins in silkworm digestive juice show antiviral activity. In this study, antiviral activity examination of different resistant strains showed that the digestive juice of the resistant strain (A35) had higher inhibition to virus than the susceptible strain (P50). Subsequently, the label-free quantitative proteomics was used to study the midgut digestive juice response to BmNPV infection in P50 and A35 strains. A total of 98 proteins were identified, of which 80 were differentially expressed proteins (DEPs) with 54 enzymes and 26 nonenzymatic proteins by comparing the proteomes of infected and non-infected P50 and A35 silkworms. These DEPs are mainly involved in metabolism, proteolysis, neuroactive ligand receptor interaction, starch and sucrose metabolism and glutathione metabolism. After removing the genetic background and individual immune stress response proteins, 9 DEPs were identified potentially involved in resistance to BmNPV. Further studies showed that a serine protease, an alkaline phosphatase and serine protease inhibitor 2 isoform X1 were differentially expressed in A35 compared to P50 or post BmNPV infection. Taken together, these results provide insights into the potential mechanisms for silkworm digestive juice to provide resistance to BmNPV infection. Signifcance: Bombyx mori nucleopolyhedrovirus (BmNPV) is highly pathogenic, which has a great impact on the sericulture. BmNPV entered the midgut lumen and exposed to digestive juices after oral infection. Previous studies have revealed that some proteins in silkworm digestive juice show antiviral activity, however, current information on the digestive juice proteome of high resistant silkworm strain after BmNPV challenge compared to susceptible strain is incomprehensive. Here, we combined label-free quantification method, bioinformatics, RT-qPCR and western blot analysis and found that BmNPV infection causes some protein changes in the silkworm midgut digestive juice. The DEPs were identified in the digestive juices of different resistant strains following BmNPV infection, and screened out some proteins potentially related to resistance to BmNPV. Three important differentially expression proteins were validated by independent approaches. These findings uncover the potential role of silkworm digestive juice in providing resistance to BmNPV and supplemented the profile of the proteome of the digestive juices in B. mori.

2.
Theriogenology ; 141: 9-15, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31479777

RESUMO

Artificial insemination (AI) has been used as a routine technology globally in the pig production industry since 1930. One of the preferable advantages of AI technology is that the semen of elite boars can be disseminated to the commercial sow population rapidly. Understanding the genetic background of semen traits may help in developing genetic improvement programs of boars by including these traits into the selection index. In this study, we utilized weighted single-step genome-wide association study (wssGWAS) to identify genetic regions and further candidate genes associated with sperm morphology abnormalities (proximal droplet, distal droplet, bent tail, coiled tail, and distal midpiece reflex) in a Duroc boar population. Several genomic regions explained 2.76%-9.22% of the genetic variances for sperm morphology abnormalities were identified. The first three detected QTL regions together explained about 7.65%-25.10% of the total genetic variances of the studied traits. Several genes were detected and considered as candidate genes for each of the traits under study: coiled tail, HOOK1, ARSA, SYCE3, SOD3, GMNN, RBPJ, STIL, and FGF1; bent tail, FGF1, ADIPOR1, ARPC5, FGFR3, PANX1, IZUMO1R, ANKRD49, and GAL; proximal droplet, NSF, WNT3, WNT9B, LYZL6, FGFR1OP, RNASET2, FYN, LRRC6, EPC1, DICER1, FNDC3A, and PFN1; distal droplet, ARSA, SYCE3, MOV10L1, CBR1, KDM6B, TP53, PTBP2, UBR7, KIF18A, ADAM15, FAAH, TEKT3, and SRD5A1; and distal midpiece reflex, OMA1, PFN1, PELP1, BMP2, GPR18, TM9SF2, and SPIN1. GO and KEGG enrichment analysis revealed the potential function of the identified candidate genes in spermatogenesis, testis functioning, and boar spermatozoa plasma membrane activating and maintenance. In conclusion, we detected candidate genes associated with the coiled tail, bent tail, proximal droplet, distal droplet, and distal midpiece reflex in a Duroc boar population using wssGWAS. Overall, these novel results reflect the polygenic genetic architecture of the studied sperm morphology abnormality traits, which may provide knowledge for conducting genomic selection on these traits. The detected genetic regions can be used in developing trait-specific marker assisted selection models by assigning higher genetic variances to these regions.

3.
Sci Total Environ ; 698: 134236, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31493577

RESUMO

The widespread emergence of antibiotic resistance genes (ARGs) in drinking water systems endangers human health, and may be exacerbated by their horizontal gene transfer (HGT) among microbiota. In our previous study, Quorum sensing (QS) molecules produced by bacteria from biological activated carbon (BAC) biofilms were demonstrated to influence the transfer efficiency of a model conjugative plasmid, here RP4. In this study, we further explored the effect and mechanism of QS on conjugation transfer. The results revealed that Acyl-homoserine lactones producing (AHL-producing) bacteria isolated from BAC biofilm play a role in the propagation of ARGs. We selected several quorum sensing inhibitors (QSIs) to study their effects on AHL-producing bacteria, including the formation of biofilm and the regulating effect on conjugation transfer. In addition, the possible molecular mechanisms for AHLs that promote conjugative transfer were attributable to enhancing the mRNA expression, which involved altered expressions of conjugation-related genes. We also found that QSIs could inhibit conjugative transfer by downregulating the conjugation-relevant genes. We believe that this is the first insightful exploration of the mechanism by which AHLs will facilitate and QSIs will inhibit the conjugative transfer of ARGs. These results provide creative insight into ARG pollution control that involves blocking QS during BAC treatment in drinking water systems.

4.
Opt Express ; 27(21): 30563-30575, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684301

RESUMO

We present an investigation on the use of oblique incidence condition to enhance the sensitivity of guided-mode resonance (GMR) sensors. By adjusting the incident angle, the enhancement of GMR sensitivity in non-subwavelength regime can be obtained. The measured results show that the bulk sensitivity of the GMR sensors with period of 809 nm climbs to 177% or 292% as the incident angle increases from 15° to 25° or 35°, respectively. The same trend is also obtained for the grating period of 994 nm. Simulations based on the rigorous coupled wave analysis (RCWA) method were performed, and we also built a new slab waveguide model to describe the relationship between bulk sensitivity and the incident angle. The present investigation demonstrates a new method for enhancing the bulk sensitivity of GMR sensor. Moreover, simple fabrication techniques can be utilized since a large grating period was used.

5.
Transbound Emerg Dis ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714018

RESUMO

H7 subtype avian influenza virus infection is an emerging zoonosis in some Asian countries and an important avian disease worldwide. A rapid and simple test is needed to confirm infection in suspected cases during disease outbreaks. In this study, we developed a reverse transcription recombinase-aided amplification assay for the detection of H7 subtype avian influenza virus. Assays were performed at a single temperature (39°C) and the results were obtained within 20 min. The assay showed no cross-detection with Newcastle disease virus or infectious bronchitis virus, which are the other main respiratory viruses affecting birds. The analytical sensitivity was 102 RNA copies per reaction at a 95% probability level according to probit regression analysis, with 100% specificity. Compared with published reverse transcription quantitative real-time polymerase chain reaction assays, the κ value of the reverse transcription recombinase-aided amplification assay in 342 avian clinical samples was 0.988 (p < .001). The sensitivity for avian clinical sample detection was 100% (95%CI, 90.40%-100%) and the specificity was 99.96% (95%CI, 97.83%-99.98%). These results indicated that our reverse transcription recombinase-aided amplification assay may be a valuable tool for detecting avian influenza H7 subtype virus.

6.
Neurosci Lett ; : 134599, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31722234

RESUMO

Expression of sphingosine/sphingosine 1-phosphate (SPH/S1P) in resident cells of the central nervous system plays an important role in the pathogenesis of multiple sclerosis (MS). Accumulated evidence has shown the protective effects of S1P receptor modulators on MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, effective therapies to regulate SPH/S1P molecules themselves have not been well addressed. Our previous studies showed that matrine (MAT), a natural alkaloid component extracted from the Sophora root, has beneficial effects in EAE through immunomodulation. Here we demonstrate that MAT alleviated astrogliosis in the CNS of EAE rats, and downregulated levels of SPH, S1P and S1P1 expression in CNS tissues and astrocytes. Expression of SPH kinases (SPHK) 1 and 2, which splice SPH into S1P, was also inhibited by MAT treatment. In vitro studies showed a direct inhibitory effect of MAT on S1P1 expression of activated astrocytes, suggesting that MAT could function as an S1PRs antagonist. Moreover, MAT upregulated the expression of plasma gelsolin, which combines with S1P to reduce its concentration. These findings indicate that MAT could alleviate astrogliosis in EAE through diminishing the SPH/SPHK/S1P1 pathway.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31694758

RESUMO

Ebola virus (EBOV) is a zoonotic pathogen, the infection often results in severe, potentially fatal, systematic disease in human and nonhuman primates. VP35, an essential viral RNA-dependent RNA polymerase cofactor, is indispensable for Ebola viral replication and host innate immune escape. In this study, VP35 was demonstrated to be phosphorylated at Serine/Threonine by immunoblotting, and the major phosphorylation sites was S187, S205, T206, S208 and S317 as revealed by LC-MS/MS. By an EBOV minigenomic system, EBOV minigenome replication was shown to be significantly inhibited by the phosphorylation-defective mutant, VP35 S187A, but was potentiated by the phosphorylation mimic mutant VP35 S187D. Together, our findings demonstrate that EBOV VP35 is phosphorylated on multiple residues in host cells, especially on S187, which may contribute to efficient viral genomic replication and viral proliferation.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31697847

RESUMO

Amyvid (florbetapir f18, [18 F]AV-45, [18 F]5) was the first FDA approved positron emission tomography (PET) imaging agent targeting ß-amyloid (Aß) plaques for assisting the diagnosis of Alzheimer's disease. This work aimed to improve the [18 F]AV-45 ([18 F]5) preparation by using solid-phase extraction (SPE) purification. [18 F]AV-45 ([18 F]5) was synthesized by direct nucleophilic radiofluorination of O-tosylated precursor (1 mg) at 120 °C in anhydrous dimethyl sulfoxide (DMSO), followed by acid hydrolysis of the N-Boc protecting group. Purification was accomplished by loading the crude reaction mixture to a cartridge (Oasis HLB 3 cc) and eluting with different combinations of solvents. This method removed the chemical impurity while leaving [18 F]AV-45 ([18 F]5) on the cartridge. The final dose was eluted by ethanol. [18 F]AV-45 ([18 F]5) was produced within 51 min (radiochemical yield 42.7 ± 5.9%, decay corrected, n = 3), and the radiochemical purity was >95%. Total chemical impurity per batch (24.1 ± 2.7 µg per batch) was below the limit described in the package insert of Amyvid, florbetapir f18 (chemical mass: less than 50 µg/dose). In summary, [18 F]AV-45 ([18 F]5) was produced efficiently and reproducibly using a cartridge-based SPE purification. This method brings the process closer for routine preparation, similar to the commercially used [18 F]FDG.

9.
J Econ Entomol ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31756251

RESUMO

Laodelphax striatellus (Fallén) is an important rice pest species which has developed high resistance to imidacloprid. Previous studies have demonstrated that CYP6AY3v2 and CYP353D1v2 were constitutively overexpressed in a imidacloprid resistant strain and can metabolize imidacloprid to mediated metabolic resistance. Further studies still needed to explore whether there are other L. striatellus P450 enzymes that can also metabolize imidacloprid. In this study, the expression level of L. striatellus CYP4C71 was significantly upregulated both in laboratory strains and field strains of L. striatellus after imidacloprid treatment for 4 h. The capability of CYP4C71 to metabolize imidacloprid was investigated. The full-length CYP4C71 was cloned, and its open reading frame was 1,515 bp with an enzyme estimated to be 505 amino acid residues in size. Furthermore, CYP4C71 was heterologously expressed along with L. striatellus cytochrome P450 reductase (CPR) in insect cells. A carbon monoxide difference spectra analysis confirmed the successful expression of CYP4C71. The recombinant CYP4C71 showed high P450 O-demethylation activity with PNP as a substrate. In vitro metabolism studies showed that recombinant CYP4C71 can metabolize imidacloprid to an easily excreted hydroxy-form. The rate of imidacloprid depletion in response to imidacloprid concentration revealed Michaelis Menten kinetics (R2 fitted curve = 0.99) with a relative low affinity: Kcat = 0.032 ± 0.009 pmol depleted imidacloprid/min/pmol P450 and Km=85.19 ± 2.93 µM. A relative big Km (85.19 ± 2.93 µM) indicated relative low imidacloprid's affinity for the CYP4C71 enzyme. In conclusion, CYP4C71 was another P450 enzyme that can metabolize imidacloprid with a relatively low affinity.

10.
Cancer Med ; 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31709750

RESUMO

BACKGROUND: Early detection of urothelial carcinoma (UC) by noninvasive diagnostic methods with high accuracy is still underscored. This study aimed to develop a noninvasive assay incorporating both enrichment of urine exfoliated cells and immunoassays for UC detection. METHODS: Polystyrene dishes were exposed to oxygen plasma and modified with 3-aminopropyltriethoxysilane to prepare amine-functionalized nanostructured substrates (NS). Performance characterization of NS was evaluated by atomic force microscope and X-ray photoelectron spectroscopy. Urine exfoliated cells were captured by NS and then immunostained to detect urinary tumor cells (UTCs), which was called UTC assay. The receiver operating characteristic (ROC) curve, area under ROC curve (AUC), and Youden index were used to find the cutoff value of UTC assay. ROC analysis and McNemar test were used to compare the diagnostic accuracy of UTC assay with cytology. Kappa test was used to analyze the agreement of UTC assay and cytology with pathological diagnosis. RESULTS: Nanostructured substrates had good cell binding yields of nucleated cells and tumor cells. CK20+ CD45- CD11b- cells were considered as UTCs. UTC number ≥ 1 per sample could be considered as a positive result. By AUC and Kappa analysis, UTC assay showed good performance in UC detection. McNemar test demonstrated that UTC assay had a superior sensitivity even in low-grade subgroup and a similar specificity compared to cytology in UC diagnosis. CONCLUSIONS: Nanostructured substrates could be used to enrich the exfoliated cells from urine samples. UTC assay with NS has the potential to play a role in UC detection. The value of this assay still needs additional validation by large, multi-center studies.

11.
Mikrochim Acta ; 186(12): 801, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31741056

RESUMO

A surface-enhanced Raman scattering (SERS) method is described for the determination of prazosin (PRH) and losartan (LOS). Silver nanoparticles modified with ß-cyclodextrin (CD-S-Ag NPs) were prepared and serve as a sensitive SERS substrate. ß-CD is both a reductant for silver ions and a host molecule that binds the analytes which leads to strong SERS enhancement. The method has distinct features: (a) The linear response extends from 0.1 to 60 µM for PRH, and from 1.0 to 100 µM for LOS; (b) the respective limits of detection are as low as 15 nM and 0.92 µM; and (c) the specific SERS bands of PRH and LOS are located at 703 and 1298 cm-1 respectively. The method was successfully applied to the determination of PRH and LOS illegally added to healthcare products. The recovery of PRH and LOS from spiked samples ranges between 91.3 and 109.3%, and from 87.4 to 105.2%, respectively, both with relative standard deviation of <5%. Graphical abstractSchematic representation of a SERS method involving ß-CD-S-Ag nanoparticles for determination of prazosin and losartan via formation of an inclusion complex.

12.
Int J Biol Sci ; 15(12): 2664-2675, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754338

RESUMO

Cys2-His2 zinc finger (C2H2-ZF) proteins represent the most common class of transcription factors. These factors have great potential for the management of developmental progression by regulating the specific spatiotemporal expression of genes. In this study, we cloned one C2H2-ZF protein gene of Bombyx mori, BGIBMGA000319, that is orthologous to B-lymphocyte-induced maturation protein-1 (Blimp-1); we thus named it as Bombyx mori Blimp-1 (BmBlimp-1). In the silkworm, the BmBlimp-1 gene is specifically upregulated during day 2 of the pupal to adult stage and is highly expressed in wing discs on day 3 of the pupa. Knockdown of its expression level in the pupal stage results in a crumpled-winged silkworm moth. Using the predicted DNA-binding sequences of BmBlimp-1 to search the silkworm genome to screen target genes of BmBlimp-1, 7049 genes were identified to have at least one binding site of BmBlimp-1 on their 1 kb upstream and downstream genome regions. Comparisons of those genes with a reported pupal wing disc transcriptome data resulted in 4065 overlapping genes being retrieved. GO enrichment analysis of the overlapping genes showed that most of the genes were enriched in the binding term. Combining functional annotation and real-time quantitative PCR, 15 genes were identified as the candidate target genes of BmBlimp-1, including several wing cuticular protein genes, chitin synthase A, and wing disc development genes, such as Wnt1, cubitus interruptus (ci) and engrailed (en). Moreover, the amino acid sequence of the zinc finger motif of Blimp-1 gene was highly conserved among the 15 insect species. We propose that BmBlimp-1 is an important regulatory factor in silkworm wing development.

13.
Vet Microbiol ; 239: 108455, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31767073

RESUMO

Clathrin-mediated endocytosis is a mechanism used for the invasion of cells by a variety of viruses. Mortalin protein is involved in a variety of cellular functions and plays a role in viral infection. In this study, we found that mortalin significantly inhibited the replication of porcine epidemic diarrhea virus (PEDV) through restricting virus entry. Mechanistically, a biochemical interaction between the carboxyl terminus of mortalin and clathrin heavy chain (CLTC) was been found, and mortalin could induce CLTC degradation through the proteasomal pathway, thereby inhibiting the clathrin-mediated endocytosis of PEDV into host cells. In addition, artificial changes in mortalin expression affected the cell entry of transferrin, further confirming the above results. Finally, we confirmed that this host-mounted antiviral mechanism was broadly applicable to other viruses, such as vesicular stomatitis virus (VSV), rotavirus (RV), and transmissible gastroenteritis virus (TGEV), which use the same clathrin-mediated endocytic to entry. These results reveal a new function of mortalin in inhibiting endocytosis, and provide a novel strategy for treating PEDV infections.

14.
Zootaxa ; 4678(1): zootaxa.4678.1.1, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31715979

RESUMO

A total of 50 (43 known and seven new) species in the subgenus Phortica (sensu stricto) were surveyed and (re)described from China: P. bicornuta (Chen Toda, 1997); P. bipartita (Toda Peng, 1992); P. biprotrusa (Chen Toda, 1998); P. cardua (Okada, 1977); P. chi (Toda Sidorenko, 1996); P. conifera (Okada, 1977); P. eparmata (Okada, 1977); P. eugamma (Toda Peng, 1990); P. excrescentiosa (Toda Peng, 1990); P. fangae (Máca, 1993); P. flexuosa (Zhang Gan, 1986); P. foliata (Chen Toda, 1997); P. gamma (Toda Peng, 1990); P. gigas (Okada, 1977); P. glabtabula Chen Gao, 2005; P. hainanensis (Chen Toda, 1998); P. hongae (Máca, 1993); P. huazhii Cheng Chen, 2008; P. iota (Toda Sidorenko, 1996); P. jadete Zhu, Cao Chen, 2018; P. kappa (Máca, 1977); P. lambda (Toda Peng, 1990); P. latifoliacea Chen Watabe, 2008; P. magna (Okada, 1960); P. okadai (Máca, 1977); P. omega (Okada, 1977); P. orientalis (Hendel, 1914); P. pangi Chen Wen, 2005; P. paramagna (Okada, 1971); P. perforcipata (Máca Lin, 1993); P. pi (Toda Peng, 1990); P. protrusa (Zhang Shi, 1997); P. pseudopi (Toda Peng, 1990); P. pseudotau (Toda Peng, 1990); P. psi (Zhang Gan, 1986); P. rhagolobos Chen Gao, 2008; P. saeta (Zhang Gan, 1986); P. setitabula Chen Gao, 2005; P. subradiata (Okada, 1977); P. tau (Toda Peng, 1990); P. uncinata Chen Gao, 2005; P. unipetala Chen Wen, 2005; P. allomega Gong Chen, sp. nov.; P. archikappa Gong Chen, sp. nov.; P. dianzangensis Gong Chen, sp. nov.; P. imbacilia Gong Chen, sp. nov.; P. liukuni Gong Chen, sp. nov.; P. tibeta Gong Chen, sp. nov.; and P. xianfui Gong Chen, sp. nov. In addition, seven new synonyms were recognized: P. acongruens (Zhang Shi, 1997), syn. nov.; P. antillaria (Chen Toda, 1997), syn. nov.; P. kukuanensis Máca, 2003, syn. nov.; P. linae (Máca Chen, 1993), syn. nov.; P. shillongensis (Singh Gupta, 1979), syn. nov.; P. takadai (Okada, 1977), syn. nov.; and P. watanabei (Máca Lin, 1993), syn. nov. A key to all Asian species (except for the eparmata species complex) of this subgenus was provided. All currently available DNA barcode (partial mitochondrial cytochrome c oxidase subunit I (COI) gene) sequences of this subgenus (217 sequences of 54 species) are employed in a molecular analysis using different species delimitation methods. The results indicate that approximately 68.5% (37 of 54 spp.) of Phortica (s. str.) species could be clearly distinguished from closely related morphospecies or cryptic species.


Assuntos
Código de Barras de DNA Taxonômico , Drosophilidae , Animais , China , Drosophilidae/genética , Extremo Oriente , Filogenia
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1062-1066, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703126

RESUMO

OBJECTIVE: To explore the spectrum of genetic variants among patients with hyperphenylalaninemia (HPA) from Quanzhou area of Fujian province. METHODS: For 63 children affected with HPA, next generation sequencing was used to identify potential variants in PAH, PTS, PCBD1, QDPR, SPR and GCH1 genes. RESULTS: Fifty two variants underlying phenylalanine hydroxylase deficiency (PAHD) and 13 variants underlying 6-pyruvoyl tetrahydropterin synthase deficiency (PTPSD) were identified. Two patients carried variants of both PAH and PTS genes. The most common variants of the PAH gene were R53H (21.69%), R241C(18.07%), R243Q(12.05%) and EX6-96A to G (7.23%), which were mainly located in exons 7 (32.53%), 2 (21.69%), 6 (9.64%) and 12 (9.64%). The L227M variant of the PAH gene was unreported previously. N52S (35.00%), P87S (25.00%), IVS1-291A to G (10.00%) and T67M (10.00%) variants were the most common variants for the PTS gene and were mainly located in exons 2 (35.00%) and 5 (35.00%). CONCLUSION: The variant spectrum underlying HPA in Quanzhou area showed a geographical specificity. A novel variant of the PAH gene (L227M) has been detected.


Assuntos
Fenilalanina Hidroxilase/genética , Fenilcetonúrias/genética , Fósforo-Oxigênio Liases/deficiência , Criança , China , Éxons , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Fósforo-Oxigênio Liases/genética
16.
Chem Commun (Camb) ; 55(93): 13967-13970, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31690896

RESUMO

A rational strategy was introduced for the synthesis of a novel dual functionalized metal-organic framework nanocomposite (AuGC/ZIF-8) with ultra-hydrophilicity to enhance glycopeptide enrichment. The advantages of ingenious synergy, low-cost, facile and large-scale synthesis, and excellent enrichment performance will enable it to have a bright future in nanomaterial synthesis, glycoproteomics analysis, and related biochemistry.

17.
Int J Drug Policy ; : 102580, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31740175

RESUMO

Network modelling is a valuable tool for simulating hepatitis C virus (HCV) and HIV transmission among people who inject drugs (PWID) and assessing the potential impact of treatment and harm-reduction interventions. In this paper, we review literature on network simulation models, highlighting key structural considerations and questions that network models are well suited to address. We describe five approaches (Erdös-Rényi, Stochastic Block, Watts-Strogatz, Barabási-Albert, and Exponential Random Graph Model) used to model partnership formation with emphasis on the strengths of each approach in simulating different features of real-world PWID networks. We also review two important structural considerations when designing or interpreting results from a network simulation study: (1) dynamic vs. static network and (2) injection only vs. both injection and sexual networks. Dynamic network simulations allow partnerships to evolve and disintegrate over time, capturing corresponding shifts in individual and population-level risk behaviour; however, their high level of complexity and reliance on difficult-to-observe data has driven others to develop static network models. Incorporating both sexual and injection partnerships increases model complexity and data demands, but more accurately represents HIV transmission between PWID and their sexual partners who may not also use drugs. Network models add the greatest value when used to investigate how leveraging network structure can maximize the effectiveness of health interventions and optimize investments. For example, network models have shown that features of a given network and epidemic influence whether the greatest community benefit would be achieved by allocating hepatitis C or HIV treatment randomly, versus to those with the most partners. They have also demonstrated the potential for syringe services and "buddy sharing" programs to reduce disease transmission.

18.
BMC Genomics ; 20(1): 797, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666004

RESUMO

BACKGROUND: In the pig production industry, artificial insemination (AI) plays an important role in enlarging the beneficial impact of elite boars. Understanding the genetic architecture and detecting genetic markers associated with semen traits can help in improving genetic selection for such traits and accelerate genetic progress. In this study, we utilized a weighted single-step genome-wide association study (wssGWAS) procedure to detect genetic regions and further candidate genes associated with semen traits in a Duroc boar population. Overall, the full pedigree consists of 5284 pigs (12 generations), of which 2693 boars have semen data (143,113 ejaculations) and 1733 pigs were genotyped with 50 K single nucleotide polymorphism (SNP) array. RESULTS: Results show that the most significant genetic regions (0.4 Mb windows) explained approximately 2%~ 6% of the total genetic variances for the studied traits. Totally, the identified significant windows (windows explaining more than 1% of total genetic variances) explained 28.29, 35.31, 41.98, and 20.60% of genetic variances (not phenotypic variance) for number of sperm cells, sperm motility, sperm progressive motility, and total morphological abnormalities, respectively. Several genes that have been previously reported to be associated with mammal spermiogenesis, testes functioning, and male fertility were detected and treated as candidate genes for the traits of interest: Number of sperm cells, TDRD5, QSOX1, BLK, TIMP3, THRA, CSF3, and ZPBP1; Sperm motility, PPP2R2B, NEK2, NDRG, ADAM7, SKP2, and RNASET2; Sperm progressive motility, SH2B1, BLK, LAMB1, VPS4A, SPAG9, LCN2, and DNM1; Total morphological abnormalities, GHR, SELENOP, SLC16A5, SLC9A3R1, and DNAI2. CONCLUSIONS: In conclusion, candidate genes associated with Duroc boars' semen traits, including the number of sperm cells, sperm motility, sperm progressive motility, and total morphological abnormalities, were identified using wssGWAS. KEGG and GO enrichment analysis indicate that the identified candidate genes were enriched in biological processes and functional terms may be involved into spermiogenesis, testes functioning, and male fertility.

19.
J Clin Invest ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31738185

RESUMO

Sustained, indolent immune injury of the vasculature of a heart transplant limits long-term graft and recipient survival. This injury is mitigated by a poorly characterized, maladaptive repair response. Vascular endothelial cells respond to proangiogenic cues in the embryo by differentiation to specialized phenotypes, associated with expression of apelin. In the adult, the role of developmental proangiogenic cues in repair of the established vasculature is largely unknown. We found that human and minor histocompatibility-mismatched donor mouse heart allografts with alloimmune-mediated vasculopathy upregulated expression of apelin in arteries and myocardial microvessels. In vivo, loss of donor heart expression of apelin facilitated graft immune cell infiltration, blunted vascular repair, and worsened occlusive vasculopathy in mice. In vitro, an apelin receptor agonist analog elicited endothelial nitric oxide synthase activation to promote endothelial monolayer wound repair, and reduce immune cell adhesion. Thus, apelin acted as an autocrine growth cue to sustain vascular repair and mitigate the effects of immune injury. Treatment with an apelin receptor agonist after vasculopathy was established markedly reduced progression of arterial occlusion in mice. Together, these initial data identify proangiogenic apelin as a key mediator of coronary vascular repair and a pharmacotherapeutic target for immune-mediated injury of the coronary vasculature.

20.
Mol Ther Nucleic Acids ; 18: 739-747, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31726390

RESUMO

5-methylcytosine (m5C) is one of the most common and abundant post-transcriptional modifications (PTCMs) in RNA. Recent studies showed that m5C plays important roles in many biological functions such as RNA metabolism and cell fate decision. Because most experimental methods that determine m5C sites across the transcriptome are time-consuming and expensive, it is urgent to develop accurate computational methods to identify m5C sites effectively. A benchmark dataset is important for developing and evaluating computational methods. In this work, we constructed four different datasets according to the data redundancy and imbalance. Based on these datasets, we generated three different kinds of features, i.e., KNFs (K-nucleotide frequencies), KSNPFs (K-spaced nucleotide pair frequencies), and pseDNC (pseudo-dinucleotide composition), and then used a support vector machine (SVM) to build our models. Based on the imbalanced and nonredundant dataset, Met935, we extensively studied the three kinds of features and determined an optimal combination of the features. Based on the feature combination, we built models on the three different datasets and compared them with state-of-the-art models. According to the predictive results of the stringent jackknife test, the models based on the three features, 4NF, 1SNPF, and pseDNC, are superior or comparable to other methods. To determine the best model between the models based on the imbalanced dataset Met935 and the balanced dataset Met240, we further evaluated the two models on an independent test set Test1157. Our results demonstrate that the model based on the balanced dataset Met240 achieved the highest recall (68.79%) and the highest Matthews correlation coefficient (MCC) (0.154). In addition, the model is also superior to other state-of-the-art methods according to the integrated parameter MCC on the independent test set. Thus, we selected the model based on Met240 as our final model, which was named RNAm5CPred. In addition, a web server for RNAm5CPred (http://zhulab.ahu.edu.cn/RNAm5CPred/) has been provided to facilitate experimental research.

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