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1.
Genome Res ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127417

RESUMO

Retrospective lineage tracing harnesses naturally occurring mutations in cells to elucidate single-cell development. Common single-cell phylogenetic fate mapping methods have utilized highly mutable microsatellite loci found within the human genome. Such methods were limited by the introduction of in vitro noise through polymerase slippage inherent in DNA amplification, which we characterized to be approximately 10-100× higher than in vivo replication mutation rate. Here, we present RETrace, a method for simultaneously capturing both microsatellites and methylation-informative cytosines to characterize both lineage and cell type, respectively, from the same single cell. A unique feature of RETrace was the introduction of linear amplification of microsatellites in order to reduce in vitro amplification noise. We further coupled microsatellite capture with single-cell reduced representation bisulfite sequencing (scRRBS), to measure the CpG methylation status on the same cell for cell type inference. When compared to existing retrospective lineage tracing methods, RETrace achieved higher accuracy (88% triplet accuracy from an ex vivo HCT116 tree) at a higher cell division resolution (lowering the required number of cell division difference between single cells by approximately 100 divisions). Simultaneously, RETrace demonstrated the ability to capture on average 150,000 unique CpGs per single cell in order to accurately determine cell type. We further formulated additional developments that would allow high-resolution mapping on microsatellite stable cells or tissues with RETrace. Overall, we present RETrace as a foundation for multiomics lineage mapping and cell typing of single cells.

2.
Curr Microbiol ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32161989

RESUMO

A novel actinobacterium, YIM 132087T, isolated from Lepraria sp. lichen collected from Yunnan province, south-west PR China. Cells are Gram-stain-positive, catalase-positive and oxidase-negative, aerobic, non-motile and short rod-shaped. Colonies are asporogenous, circular and white brown in colour. Optimal growth occured at 15-35 °C (optimum 28 °C), at pH 5.0-9.0 (optimum pH 6.0), and in the presence of 3% NaCl (w/v). The DNA G+C content of strain YIM 132087T based on the draft genome sequence was 71.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences suggested that strain YIM 132087T belonged to the genus Nakamurella and exhibited high levels of 16S rRNA gene sequence similarity with Nakamurella endophytica CGMCC 4.7038T (97.9%) and Nakamurella intestinalis NBRC 111844T (97.2%). The DNA-DNA hybridization values between strain YIM 132087T and its closest relatives are lower than 26%. Strain YIM 132087T had meso-diaminopimelic acid as the diagnostic cell-wall diamino acid, and MK-8(H4) as the predominant menaquinone. Predominant cellular fatty acids (> 10%) were iso-C16:0, iso-C15:0, C16:0 and anteiso-C15:0. The polar lipid profile were found to be diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylinositol, three unknown phospholipids, one unknown aminophospholipid and one unknown lipid. Based on phenotypic, phylogenetic and chemotaxonomic analysis, strain YIM 132087T belongs to the genus Nakamurella and represents a novel species of the genus Nakamurella, for which the name Nakamurella albus sp. nov., with type strain YIM 132087T (=CGMCC 4.7629T =NBRC 114017T), is proposed.

3.
Clin Pharmacol Ther ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32141068

RESUMO

In a general inpatient population, we predicted patient-specific medication orders based on structured information in the electronic health record. Data on over 3 million medication orders from an academic medical center were used to train two machine learning models: a deep learning sequence model and a logistic regression model. Both were compared to a baseline that ranked the most frequently ordered medications based on a patient's discharge hospital service and amount of time since admission. Models were trained to predict from 990 possible medications at the time of order entry. Fifty five percent of medications ordered by physicians were ranked in the sequence model's top-10 predictions (logistic model: 49%) and 75% ranked in the top-25 (logistic model: 69%). Ninety-three percent of the sequence model's top-10 prediction sets contained at least one medication that physicians ordered within the next day. These findings demonstrate that medication orders can be predicted from information present in the electronic health record.

4.
Dig Dis Sci ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193861

RESUMO

BACKGROUND: Pain associated with colonoscopies is a major barrier to patients participating in colorectal cancer screenings. While sedation and analgesia are used to reduce pain during the procedure, they are associated with increased complications and costs. Thus, it is necessary to identity novel techniques to relieve pain in a safe and cost-effective way. AIMS: To test whether watching real-time videos of colonoscopies while receiving detailed interpretations of the procedures reduces pain and anxiety and increases a patient's satisfaction. METHODS: Patients were randomized into three groups including a group who watched real-time videos of their colonoscopies (Group A), a group who watched real-time videos of their colonoscopies while receiving detailed interpretations of the procedures from the endoscopists (Group B), and a group who did not receive either method (Group C). RESULTS: Pain and anxiety scores were significantly (Group A vs. Group C, [Formula: see text]; Group B vs. Group C, [Formula: see text]) lower in Groups A and B compared to Group C. Additionally, significantly (Group A vs. Group C, [Formula: see text]; Group B vs. Group C, [Formula: see text]) increased satisfaction was observed in Groups A and B compared to Group C. There were no statistically significant differences observed in the pain and anxiety scores when comparing Groups A and B. However, the overall satisfaction score was significantly ([Formula: see text]) higher in Group B compared to Group A. CONCLUSIONS: Real-time videos of colonoscopies as well as videos along with detailed interpretations of the procedures decrease pain and anxiety while improving satisfaction in patients undergoing colonoscopies without sedation. Videos combined with interpretations lead to a greater increase in patient satisfaction.

5.
Adv Sci (Weinh) ; 7(6): 2000588, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195106

RESUMO

[This corrects the article DOI: 10.1002/advs.201900099.].

6.
Org Lett ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32195591

RESUMO

Photocatalytic and metal-free protocols to access various aromatic and heteroaromatic nitro compounds through ipso-nitration of readily available boronic acid derivatives were developed using non-metal-based, bench-stable, and recyclable nitrating reagents. These methods are operationally simple, mild, regioselective, and possess excellent functional group compatibility, delivering desired products in up to 99% yield.

7.
BMC Endocr Disord ; 20(1): 42, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32209072

RESUMO

BACKGROUND: 47,XYY is a chromosomal abnormality syndrome that is typically observed in patients with a male phenotype. Few patients with XYY syndrome will have infertility. We here report a case of 46,XY/47,XYY syndrome diagnosed in a patient with a female phenotype. CASE PRESENTATION: A 15-year-old patient with a female phenotype visited our hospital owing to a chief complaint of short stature as of the age of 6 years. She was diagnosed with dwarf syndrome at the age of 10, but no change was noted after 2 months of growth hormone treatment. The patient's height was 136 cm and the weight was 29 kg, both of which were below the third percentile for her age/gender. In addition to short stature, the 4th and 5th metacarpals were short and there was no significant sex development. Karyotype analysis showed 47,XYY, and chromosomal microarray examination showed a chimera of 46,XY/47,XYY. CONCLUSION: This is an extremely rare case of 47,XYY abnormality in a patient with a female phenotype, with only one such known case reported previously. Since the cause is unknown, and symptoms of this syndrome are highly atypical and variable in childhood, clinicians should be aware of this possibility to avoid misdiagnosis and offer counseling and hormone therapy as needed to patients and their parents to improve their quality of life.

8.
Sci Total Environ ; 719: 137454, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32114233

RESUMO

Phaeocystis globosa is a major causative agent of harmful algal blooms in the global ocean, featuring a complex polymorphic life cycle alternating between free-living solitary cells and colonial cells. Colony is the dominant morphotype during P. globosa bloom. However, the underlying mechanism of colony formation is poorly understood. Here, we comprehensively compared global transcriptomes of P. globosa cells at four distinctive colony formation stages: free-living solitary cells, two cell-, four cell- and multi-cell colonies, under low (20 °C) and high (32 °C) temperatures, and characterized the genes involved in colony formation. Glycosaminoglycan (GAG) synthesis was enhanced while its degradation was decreased during colony formation, resulting in the accumulation of GAGs that are an essential substrate of the colony matrix. Nitrogen metabolism and glutamine synthesis were remarkably increased in the colonial cells, which provided precursors for GAG synthesis. Furthermore, cell defense and motility were down-regulated in the colonial cells, thereby conserving energy for GAG synthesis. Notably, high temperature led to decreased synthesis and increased degradation of GAGs, resulting in insufficient substrates to form the colony. Our study indicates that GAGs accumulation is critical for colony formation of P. globosa, but high temperature inhibits GAGs' accumulation and colony formation.

9.
Eur J Med Chem ; 192: 112161, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32155529

RESUMO

KDM5B (also known as PLU-1 and JARID1B) is 2-oxoglutarate and Fe2+ dependent oxygenase that acts as a histone H3K4 demethylase, which is a key participant in inhibiting the expression of tumor suppressors as a drug target. Here, we present the discovery of pyrazole derivatives compound 5 by structure-based virtual screening and biochemical screening with IC50 of 9.320 µM against KDM5B, and its subsequent optimization to give 1-(4-methoxyphenyl)-N-(2-methyl-2-morpholinopropyl)-3-phenyl-1H-pyrazole-4-carboxamide (27 ab), a potent KDM5B inhibitor with IC50 of 0.0244 µM. In MKN45 cells, compound 27 ab can bind and stabilize KDM5B and induce the accumulation of H3K4me2/3, bona fide substrates of KDM5B, while keep the amount of H3K4me1, H3K9me2/3 and H3K27me2 without change. Further biological study also indicated that compound 27 ab is a potent cellular active KDM5B inhibitor that can inhibit MKN45 cell proliferation, wound healing and migration. In sum, our finding gives a novel structure for the discovery of KDM5B inhibitor and targeting KDM5B may be a new therapeutic strategy for gastric cancer treatment.

10.
Curr Med Sci ; 40(1): 9-17, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32166660

RESUMO

This study aimed to develop a novel surgery classification for an endoscopic approach to middle ear cholesteatoma. We retrospectively analyzed the surgical approaches and outcomes of patients with middle ear cholesteatoma. Middle ear cholesteatoma surgeries were divided into four types and two special types as follows: type I, attic retraction pocket, which only requires tympanostomy tube placement or retraction pocket resection and cartilage reconstruction; type II, cholesteatoma which is limited to the attic or in which endoscopy can confirm complete removal of mastoid cholesteatoma lesions, including type II a, requiring only use of a curette, and type II b, requiring use of an electric drill or chisel; type III, cholesteatoma not limited to the attic, in which endoscopy cannot confirm complete removal of mastoid cholesteatoma lesions, requiring the combined use of endoscope and microscope to perform endoscopic tympanoplasty and "Canal Wall Up" mastoidectomy; type IV, extensive involvement of mastoid cavity cholesteatoma lesions and/or cases with a potential risk of complications, removal of which can only be performed under a microscope for "Canal Wall Down" mastoidectomy. In addition, there were two special types: "difficult external auditory canal" and congenital cholesteatoma in children. In our system, type I and type II middle ear cholesteatoma surgery was completely performed under an endoscope alone. However, estimating the extent of the lesions, determining the choice of mastoid opening and reestablishing ventilation are the key points for an endoscopic approach to middle ear cholesteatoma. The classification of endoscopic middle ear cholesteatoma surgery may benefit the selection of surgical indications.

11.
Bioorg Chem ; 98: 103757, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32217370

RESUMO

Carbamyl is considered a privileged structure in medicinal chemistry. It has a wide range of biological activities such as antimicrobial, anticancer, anti-epilepsy, for which the best evidence is a number of marketed carbamyl-containing drugs. Carbamyl is formed of primary amine and carbonyl moieties that act as hydrogen bond donors and hydrogen acceptors with residues of targets respectively, which are benefit for improving pharmacological activities. In other cases, the introduced carbamyl improves drug-like properties including oral bioavailability. In this review, we introduce the carbamyl-containing drugs and the application of carbamyl in structural optimization as a result of enhancing activities or/and drug-like properties.

12.
Nat Rev Nephrol ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221477

RESUMO

Breakthroughs in the development of high-throughput technologies for profiling transcriptomes at the single-cell level have helped biologists to understand the heterogeneity of cell populations, disease states and developmental lineages. However, these single-cell RNA sequencing (scRNA-seq) technologies generate an extraordinary amount of data, which creates analysis and interpretation challenges. Additionally, scRNA-seq datasets often contain technical sources of noise owing to incomplete RNA capture, PCR amplification biases and/or batch effects specific to the patient or sample. If not addressed, this technical noise can bias the analysis and interpretation of the data. In response to these challenges, a suite of computational tools has been developed to process, analyse and visualize scRNA-seq datasets. Although the specific steps of any given scRNA-seq analysis might differ depending on the biological questions being asked, a core workflow is used in most analyses. Typically, raw sequencing reads are processed into a gene expression matrix that is then normalized and scaled to remove technical noise. Next, cells are grouped according to similarities in their patterns of gene expression, which can be summarized in two or three dimensions for visualization on a scatterplot. These data can then be further analysed to provide an in-depth view of the cell types or developmental trajectories in the sample of interest.

13.
Anim Sci J ; 91(1): e13326, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32219924

RESUMO

Antibiotics stimulate the growth of animals but result in drug residues and bacterial resistance. In this study, the negative effect of antibiotics on abdominal fat deposition was evaluated in broilers. The results showed that adding both chlortetracycline (50 g/1,000 kg) and tylosin (50 g/1,000 kg) significantly increased abdominal fat weight, abdominal fat percentage (p < .05), and triglyceride and cholesterol levels (p < .05) in blood. Also, both products synchronously stimulated intestinal absorption and synthesis of liver fat. The expression levels of the peroxisome proliferator-activated receptor Î³ (PPARγ), diacylgycerol acyltransferase 2 (DGAT2), lipoprotein lipase (LPL), and fatty acid-binding protein (FABP4) genes in abdominal fat tissue significantly increased (p < .05 or 0.01) when antibiotics were added to the feed. However, no significant difference was found in expression of the fatty acid synthesis (FAS) or acetyl CoA carboxylase (ACC) genes. Further in vitro study results revealed that antibiotics had no effect on fat content or the related gene expression levels in preadipocytes. In summary, the antibiotics induced fat deposition in adipose tissues by activating extracellular absorption of fatty acids from intestinal absorption and synthesis of liver fat. However, it shows no direct regulation by adipose tissue.

14.
Sci Rep ; 10(1): 4262, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144352

RESUMO

Liver-enriched gene 1 (Leg1) is a newly identified gene with little available functional information. To evolutionarily and molecularly characterize Leg1 genes, a phylogenetic study was first conducted, which indicated that Leg1 is a conserved gene that exists from bacteria to mammals. During the evolution of mammals, Leg1s underwent tandem duplications, which gave rise to Leg1a, Leg1b, and Leg1c clades. Analysis of the pig genome showed the presence of all three paralogs of pig Leg1 genes (pLeg1s), whereas only Leg1a could be found in the human (hLeg1a) or mouse (mLeg1a) genomes. Purifying force acts on the evolution of Leg1 genes, likely subjecting them to functional constraint. Molecularly, pLeg1a and its coded protein, pig LEG1a (pLEG1a), displayed high similarities to its human and mouse homologs in terms of gene organization, expression patterns, and structures. Hence, pLeg1a, hLeg1a, and mLeg1a might preserve similar functions. Additionally, expression analysis of the three Leg1as suggested that eutherian Leg1as might have different functions from those of zebrafish and platypus due to subfunctionalization. Therefore, pLeg1a might provide essential information about eutherian Leg1a. Moreover, a preliminary functional study using RNA-seq suggested that pLeg1a is involved in the lipid homeostasis. In conclusion, our study provides some basic information on the aspects of evolution and molecular function, which could be applied for further validation of Leg1 using pig models.

15.
J Nutr Biochem ; 79: 108353, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32145470

RESUMO

Probiotics are known to be beneficial in preventing different diseases in model animals, including inflammatory bowel disease. However, there are few studies on probiotics related to miRNA regulation and disease status. In this article, the beneficial role and mechanisms of the probiotic strain Bifidobacterium bifidum ATCC 29521 have been studied in ulcerative colitis using dextran sodium sulphate (DSS) model. Male C57JBL/6 mice were randomly divided into three groups (n=7): Normal group, dextran sulphate sodium (DSS) group, and Bifido group gavage with Bifidobacterium bifidum ATCC 29521 (2×108 CFU/day). Our strain restored the DSS-caused damage by regulating the expression of immune markers and tight junction proteins (TJP) in the colon; briefly by up-regulating ROS-scavenging enzymes (SOD1, SOD2, CAT, and GPX2), anti-inflammatory cytokines (IL-10, PPARγ, IL-6), TJP's (ZO-1, MUC-2, Claudin-3, and E Cadherin-1) and downregulating inflammatory genes (TNF-α, IL-1ß) in Bifido group mice. Inflammatory markers appeared to be regulated by NF-κB nuclear P65 subunit, and its translocation was inhibited in Bifido group mice colon. In addition, the expression of inflammatory genes and colonic TJP were also associated with the restoration of miRNAs (miR-150, miR-155, miR-223) in B. bifidum ATCC 29521 treated Bifido group. The dysbiosis executed by DSS was restored in the Bifido group, demonstrating that B. bifidum ATCC 29521 possessed a probiotic role in our DSS colitis mouse model. B. bifidum ATCC 29521 exhibited its probiotic role through its anti-inflammatory role by modulating miRNA-associated TJP and NF-κB regulation and by partially restoring dysbiosis.

18.
Int Immunopharmacol ; 82: 106377, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32163858

RESUMO

BACKGROUND: CTLA-4 is involved in the immune dysfunction of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study analyzed the association of circulating CTLA-4 levels and CTLA4 polymorphisms with disease condition and progression in chronic HBV infection. METHODS: Serum CTLA-4 levels and CTLA4 rs231775 and rs5742909 polymorphisms were determined in patients with various HBV-related diseases [53 asymptomatic HBV carrier status (ASC), 147 chronic hepatitis, 130 cirrhosis and 102 HCC] and nearly a 10-year follow-up. RESULTS: Serum CTLA-4 levels were stepwisely increased from ASC, chronic hepatitis, cirrhosis to HCC and independently associated with HCC (OR 2.628, P < 0.001). HCC patients had lower frequencies of rs231775 genotype GA, genotype AA and allele A than ASC, chronic hepatitis and cirrhosis patients. Rs231775 genotype GG was independently associated with HCC (OR 2.324, P = 0.010) and higher CTLA-4 levels in patients with HBV infection. In the follow-up, higher baseline CTLA-4 levels and CTLA4 rs231775 genotype GG significantly associated with disease progression from chronic hepatitis to cirrhosis (OR 2.561, P = 0.011 and OR 2.799, P = 0.015, respectively) or from cirrhosis to HCC (OR 2.673, P = 0.008 and OR 2.097, P = 0.023, respectively) and with a shorter overall survival in HCC patients (HR 0.317, P = 0.018 and HR 0.682, P = 0.026, respectively). Rs5742909 had no significant association with CTLA-4 levels and disease progression. CONCLUSION: CTLA-4 levels and CTLA4 rs231775 polymorphism associate with the disease condition and progression and HCC development in chronic HBV infection and their determination may be used for monitoring disease progression and predicting patient prognosis.

19.
Aging (Albany NY) ; 122020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32181755

RESUMO

OBJECTIVE: The tumour microenvironment is one of the significant factors driving the carcinogenesis of Pancreatic adenocarcinoma (PAAD). However, the underlying mechanism of how the tumour microenvironment impacts the prognosis of PAAD is not completely clear. RESULTS: The transcriptome and clinical data of 182 PAAD program cases were downloaded from the TCGA database. Three hundred thirty-three differentially expressed genes (DEGs) between high and low stromal groups and 314 DEGs between high and low immune score groups were identified using ESTIMATE score. Based on the 203 genes differentially expressed simultaneously in two score-related comparisons, we established an 8-mRNA signature to evaluate the prognosis of PAAD patients. Kaplan-Meier curves showed significantly worse survival for patients with high-risk scores in both the training and validation groups. The risk score was an independent prognostic factor and had a high predictive value for the prognosis of patients with PAAD. By searching the TCGA database, we showed that CA9, CXCL9, and GIMAP7 from the 8-mRNA signature were associated with the infiltration levels of immunocytes by regulating FOXO1 expression in PAAD. CONCLUSIONS: Unlike traditional methods of screening for differential genes in cancer and healthy tissues, we constructed a novel 8-mRNA signature to predict the prognosis of PAAD patients by applying ESTIMATE scoring to RNA-seq-based transcriptome data. Most importantly, we identified CA9, CXCL9, and GIMAP7 from the above eight genes as regulators of immunocyte infiltration by adjusting the expression of FOXO1 in PAAD. Thus, CA9, CXCL9, and GIMAP7 might be the ideal targets of immune therapy of PAAD. METHODS: ESTIMATE scoring was used to determine the stromal and immune scores of transcriptome datasets downloaded from the TCGA database. An mRNA-based prognostic signature was built for the training cohort via the LASSO Cox regression model. The signature was verified using a validation cohort. Kaplan-Meier curves and log-rank analysis were used to identify survival differences. Western blot analysis and RT-qPCR analysis were carried out to analyze the expression of specific proteins and mRNAs. IHC was performed to assess the protein levels of Forkhead box-O 1 (FOXO1), Carbonic anhydrase 9 (CA9), C-X-C motif chemokine ligand 9 (CXCL9), and GTPase, IMAP family member 7 (GIMAP7) in the tissue microarray of PAAD.

20.
Ecotoxicol Environ Saf ; 194: 110435, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32169728

RESUMO

Soil salinization is one of most crucial environmental problems around the world and negatively affects plant growth and production. Carex rigescens is a turfgrass with favorable stress tolerance and great application prospect in salinity soil remediation and utilization; however, the molecular mechanisms behind its salt stress response are unknown. We performed a time-course transcriptome analysis between salt tolerant 'Huanghua' (HH) and salt sensitive 'Beijing' (BJ) genotypes. Physiological changes within 24 h were observed, with the HH genotype exhibiting increased salt tolerance compared to BJ. 5764 and 10752 differentially expressed genes were approved by transcriptome in BJ and HH genotype, respectively, and dynamic analysis showed a discrepant profile between two genotypes. In the BJ genotype, genes related to carbohydrate metabolism and stress response were more active and ABA signal transduction pathway might play a more important role in salt stress tolerance than in HH genotype. In the HH genotype, unique increases in the regulatory network of transcription factors, hormone signal transduction, and oxidation-reduction processes were observed. Moreover, trehalose and pectin biosynthesis and chitin catabolic related genes were specifically involved in the HH genotype, which may have contributed to salt tolerance. Moreover, some candidate genes like mannan endo-1,4-beta-mannosidase and EG45-like domain-containing protein are highlighted for future research about salt stress resistance in C. rigescens and other plant species. Our study revealed unique salt adaptation and resistance characteristics of two C. rigescens genotypes and these findings could help to enrich the currently available knowledge and clarify the detailed salt stress regulatory mechanisms in C. rigescens and other plants.

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