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1.
Clin Nutr ; 40(5): 2535-2542, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33932800

RESUMO

BACKGROUND & AIMS: Malnutrition is associated with poor prognosis of different diseases. This study aimed to investigate the association of malnutrition with long-term mortality of older adults with ischemic stroke in China. METHODS: We selected patients aged ≥65 years with first-ever ischemic stroke from the Nanjing Stroke Registry Program. Malnutrition was defined according to the controlling nutritional status score (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index score (PNI), respectively. Multivariable Cox proportional hazards regressions and competing risk regressions were performed to explore the relationship between malnutrition and the risk of mortality in older adults with ischemic stroke. RESULTS: Among 1065 enrolled patients, 60.5%, 46.7%, and 30.6% of patients were malnourished according to CONUT, GNRI, and PNI score. During a median follow-up of 4.74 (3.73-5.82) years, 205 (19.2%) patients died. In multivariate analysis, malnutrition (severe risk versus normal nutrition) was associated with significantly increased risk for mortality by the CONUT (adjusted hazard ratio [HR] 4.615, 95% confidence interval [CI] 1.373-15.514, P = 0.013), GNRI (adjusted HR 3.641, 95% CI 1.924-6.891, P < 0.001), and PNI score (adjusted HR 1.587, 95% CI, 1.096-2.297, P = 0.014). Furthermore, adding the malnutrition indexes to models modestly improved the predictive ability of mortality. CONCLUSIONS: Our study indicated that malnutrition was highly prevalent in older Chinese adults with ischemic stroke and associated with increased mortality. Further research is required to evaluate the efficacy of nutritional management in these patients.

2.
Food Chem ; 356: 129728, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33836362

RESUMO

Alginate is a low-cost polysaccharide found abundantly in seaweeds which consists of mannuronate and guluronate, and it is considered a sustainable gum source for dietary fiber. To solve the high viscosity-related problems while retaining its physiological properties, four partially degraded alginate products (PDA1-4) with molecular weight of 1.05-0.40 × 105 g mol-1 and intrinsic viscosity of 170.9-38.9 mL g-1 were enzymatically prepared and characterized. 1H Nuclear magnetic resonance analysis showed the used alginate lyase had a preference to degrade guluronate-blocks. PDA1 and PDA2 presented random coil conformation, whereas PDA3 and PDA4 displayed compact spherical-coil conformation over random coil conformation in solution. In vitro assays suggested a glucose-adsorption capacity order of PDA1 < PDA2 < alginate < PDA3 < PDA4 and a glucose-diffusion retardation capacity order of PDA3 < PDA1 ≤ alginate < PDA2 < PDA4, indicating that partially degraded alginate reinforced the hypoglycemic effect, especially mannuronate-rich PDA4. Overall, the study may have important implications for development of PDA as dietary fiber with potential hypoglycemic activity.

3.
Biomed Res Int ; 2021: 6670456, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33824876

RESUMO

Background: Cervical cancer (CC) is the second most common tumor in women worldwide. Studies have been accepted that genetic variations play an important role in the development of CC. The aim of this study was to evaluate the impact of TCF7L1 variants on CC risk. Methods: 508 patients of cervical cancer and 497 healthy subjects were recruited to determine the impact of TCF7L1 polymorphisms on CC susceptibility. The associations were investigated by computing odds ratios (ORs) and 95% confidence intervals. The effect of SNP-SNP interactions on CC risk was explored by multifactor dimensionality reduction analysis. Results: Our study showed that rs11904127 (OR 0.79, p = 0.010) and rs62162674 (OR 0.82, p = 0.044) of TCF7L1 significantly decreased cervical cancer risk. Stratified analysis indicated that rs11904127 and rs62162674 present decreased susceptibility to CC in age > 51 years (OR 0.74, p = 0.019; OR 0.72, p = 0.014, respectively). Haplotype analyses revealed that Grs2366264Trs11689667Crs62162674 has a lower risk to cervical cancer (OR = 0.43, p = 0.018). Besides, there is strong interaction of rs11904127 and rs2366264. Conclusion: Rs11904127 and rs62162674 in TCF7L1 are related to cervical cancer. We suggest that these variants can be used as prognostic markers for judging the susceptibility to cervical cancer.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33792135

RESUMO

Enantiomers of 2, 6-diaminotriptycene (R, R-1 and S, S-1) are split by chiral-phase HPLC and their absolute configurations are identified by single-crystal X-ray diffraction technology. Using the enantiomers as monomers, a couple of chiral porous polyimides (R-FTPI and S-FTPI) are prepared by polycondensation reactions and display good heat stability, high BET surface area and good solubility in organic solvents. Moreover, both of R-FTPI and S-FTPI can be cast into robust, free-standing films suitable for enantioselective separation with symmetrical chiral selectivity.

5.
Enzyme Microb Technol ; 145: 109747, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33750537

RESUMO

d-tagatose is a functional sweetener that occurs in small quantity in nature. It is mainly produced through the isomerization of d-galactose by l-arabinose isomerase (l-AI; EC 5.3.1.4). However, the cost of d-galactose is much higher than those commonly used for the production of functional sweeteners such as glucose, maltodextrin, or starch. Here, a multi-enzyme catalytic system consists of five enzymes that utilizes maltodextrin as substrate to synthesize d-tagatose were co-expressed in E. coli, resulting in recombinant cells harboring the plasmids pETDuet-αgp-pgm and pCDFDuet-pgi-gatz-pgp. The activity of this whole-cell catalyst was optimal at 60 °C and pH 7.5, and 1 mM Mg2+ and 50 mM phosphate were the optimal cofactors for activity. Under the optimal reaction conditions, 2.08 and 3.2 g L-1d-tagatose were produced by using 10 and 20 g L-1 maltodextrin as substrates with recombinant cells for 24 h. This co-expression system provides a one-pot synthesis approach for the production of d-tagatose using inexpensive substrate, avoiding enzymes purification steps and supplementation of expensive cofactors.

6.
Life Sci ; : 119092, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33737086

RESUMO

AIMS: Phenotypic switching of vascular smooth muscle cells (VSMCs) is essential for the formation of abdominal aortic aneurysms (AAAs). MicroRNA-23b (miR-23b) has recently been shown to play a vital role in maintaining the VSMC contractile phenotype; however, little is known about the role of miR-23b in the formation of AAAs. Here, we investigated whether miR-23b prevents AAA formation by inhibiting VSMC phenotypic switching. MATERIALS AND METHODS: We administered angiotensin II (Ang II, 1000 ng/kg/min) or vehicle to 10-12-week-old male apolipoprotein E knockout (ApoE-/-) or C57BL/6J mice via subcutaneous osmotic minipumps for 4 weeks. KEY FINDINGS: The expression of miR-23b was significantly reduced in the aorta during the early onset of AAA in angiotensin II-treated ApoE-/- mice and in human AAA samples. In vitro experiments showed that the suppression of SMC contractile marker gene expression induced by Ang II was accelerated by miR-23b inhibitors but inhibited by mimics. In vivo studies revealed that miR-23b deficiency in Ang II-treated C57BL/6J mice aggravated the formation of AAAs in these mice compared with control mice; the opposite results were observed in miR-23b-overexpressing mice. Mechanistically, miR-23b knockdown significantly increased the expression of the transcription factor forkhead box O4 (FoxO4) during VSMC phenotypic switching induced by Ang II. In addition, a luciferase reporter assay showed that FoxO4 is a target of miR-23b in VSMCs. SIGNIFICANCE: Our study revealed a pivotal role for miR-23b in protecting against aortic aneurysm formation by maintaining the VSMC contractile phenotype.

7.
J Sci Food Agric ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608926

RESUMO

BACKGROUND: Alginate lyases (EC 4.4.2.3/4.4.2.11) have been applied to produce alginate oligosaccharides, which have physiological advantages such as prebiotic and antidiabetic effects, and are of benefit in the food and pharmaceutical industries. Extracellular production of recombinant proteins in Escherichia coli presents advantages including simplified downstream processing and high productivity; however, the presence of certain signal peptides does not always ensure successful secretion, which make the extracellular production of alginate lyase in E. coli rarely reported but of great significance. RESULTS: A PL7 family alginate lyase, Aly01, with its native signal peptide from Vibrio natriegens SK42.001, was identified, characterized, and extracellularly expressed in E. coli. The enzyme specifically released trisaccharide from alginate and was strictly NaCl activated. Green fluorescent protein (GFP) was fused with the Aly01 signal peptide and successfully secreted in E. coli to expand the feasibility of using this signal peptide to produce other heterologous proteins extracellularly. Through a synergistic strategy of utilizing Terrific Broth (TB) medium supplemented with 120 mmol L-1 glycine and 10 mmol L-1 calcium, the lag phase of protein secretion was reduced to 3 h from 12 h; meanwhile calcium remedied glycine-related cell growth impairment, leading to further enhancement of overall enzyme productivity, reaching a maximum of 4.55 U mL-1 . CONCLUSION: A new salt-activated alginate lyase, Aly01, was identified and characterized. E. coli employed its signal peptide and extracellularly expressed both Aly01 and a GFP, which indicated the signal peptide of Aly01 could be a powerful tool for extracellular production of other heterologous proteins in E. coli. © 2021 Society of Chemical Industry.

8.
Water Res ; 193: 116891, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33582495

RESUMO

There is considerable concern around the use of new psychoactive substances (NPS), but still little is known about how much they are really consumed. Analysis by forensics laboratories of seized drugs and post-mortem samples as well as hospital emergency rooms are the first line of identifying both 'new' NPS and those that are most dangerous to the community. However, NPS are not necessarily all seized by law enforcement agencies and only substances that contribute to fatalities or serious afflictions are recorded in post-mortem and emergency room samples. To gain a better insight into which NPS are most prevalent within a community, complementary data sources are required. In this work, influent wastewater was analysed from 14 sites in eight countries for a variety of NPS. All samples were collected over the 2019/2020 New Year period, a time which is characterized by celebrations and parties and therefore a time when more NPS may be consumed. Samples were extracted in the country of origin following a validated protocol and shipped to Australia for final analysis using two different mass spectrometric strategies. In total, more than 200 were monitored of which 16 substances were found, with geographical differences seen. This case study is the most comprehensive wastewater analysis study ever carried out for the identification of NPS and provides a starting point for future, ongoing monitoring of these substances.


Assuntos
Drogas Ilícitas , Transtornos Relacionados ao Uso de Substâncias , Austrália , Humanos , Psicotrópicos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Águas Residuárias/análise
9.
Clin Pharmacokinet ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544318

RESUMO

BACKGROUND AND OBJECTIVES: The safety of inflammatory bowel disease medications during lactation is of significant relevance to women of childbearing potential. Available data regarding the transfer of biologic agents for inflammatory bowel disease via breast milk are limited to case reports. The objective of this prospective postmarketing lactation study was to assess vedolizumab concentrations in breast milk from lactating vedolizumab-treated women with inflammatory bowel disease. METHODS: Breast milk was serially collected throughout the dosing interval from 11 patients receiving established intravenous vedolizumab 300-mg maintenance therapy every 8, 6, or 4 weeks. Maternal safety was also assessed. RESULTS: Vedolizumab was detectable in ~90% of milk samples collected from all patients. Following the day 1 dose, vedolizumab milk concentrations increased with a median of 3-4 days to peak concentration, and subsequently decreased exponentially. For the nine patients receiving vedolizumab every 8 weeks, the average relative infant dose was 20.9%. Using a mean trough serum concentration of 11.2 µg/mL from historical studies, the ratio of mean vedolizumab milk-to-serum concentration was ~ 0.4 to 2.2%, consistent with published data on vedolizumab and other monoclonal antibody therapeutics for inflammatory bowel disease. The maternal safety profile was similar to that observed in previous vedolizumab studies. Published vedolizumab studies also showed no adverse findings for infants breastfed by vedolizumab-treated mothers. CONCLUSIONS: Vedolizumab was present in human breast milk at a low level. The decision to use vedolizumab should balance the benefit of therapy to the mother and the potential risks to the infant. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02559713; registered 24 September, 2015.

10.
Mol Cell Biochem ; 476(4): 1651-1661, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33420899

RESUMO

JS-K as an exogenous NO donor could release NO after activation by glutathione S-transferases (GSTs). The present study explores the effects of JS-K on MAPK pathway in HepG2 and Bel-7402 cells. JS-K significantly prompted apoptosis and SB203580 (a p38 inhibitor) and SP600125 (a JNK inhibitor) prior to JS-K could partly reverse apoptosis and activation of cleaved-caspase-3 and cleaved PARP. However, U0126 (a MEK inhibitor) strengthened the cell apoptosis and the expressions of cleaved-caspase-3 and cleaved PARP. JS-K caused phosphorylation of p38 MAPK and JNK but attenuated phosphorylation of ERK, which were reversed by Carboxy-PTIO (a NO scavenger). Meanwhile, the phosphorylation of HSP27, c-JUN and ATF-2 were activated in JS-K-treated cells. SB203580 and SP600125 could attenuate phosphorylation of p38 MAPK and JNK, respectively. The phosphorylation in downstream substrates of p38 MAPK and JNK was also abolished by SB203580 and SP600125 in JS-K-treated cells. Additionally, JS-K decreased phosphorylation of c-Raf, which subsequently caused a decrease of MEK1/2 phosphorylation. Several downstream targets of ERK1/2 including p90RSK and transcription factors (e.g., Elk-1, c-Myc and c-Fos) were inhibited. U0126 potentiated JS-K-induced inhibitory effect of Raf/MEK/ERK pathway. The same results were also observed in the downstream substrates of ERK1/2 including p90RSK, Elk-1, c-Myc and c-Fos. Moreover, Carboxy-PTIO abolished the inhibitory effect of Raf/MEK/ERK pathway triggered by JS-K. Finally, JS-K significantly suppressed the growth of rat primary hepatic carcinoma via MAPK pathway in vivo. Taken together, JS-K can induce hepatocellular carcinoma cells apoptosis through its activation of JNK and p38 MAPK and inactivation of Raf/MEK/ERK signaling pathways.

11.
Neurochem Res ; 46(3): 660-674, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33392910

RESUMO

Depression afflicts more than 300 million people worldwide, but there is currently no universally effective drug in clinical practice. In this study, chronic restraint stress (CRS)-induced mice depression model was used to study the antidepressant effects of resveratrol and its mechanism. Our results showed that resveratrol significantly attenuated depression-like behavior in mice. Consistent with behavioral changes, resveratrol significantly attenuated CRS-induced reduction in the density of dendrites and dendritic spines in both hippocampus and medial prefrontal cortex (mPFC). Meanwhile, in hippocampus and mPFC, resveratrol consistently alleviated CRS-induced cofilin1 activation by increasing its ser3 phosphorylation. In addition, cofilin1 immunofluorescence distribution in neuronal inner peri-membrane in controls, and cofilin1 diffusely distribution in the cytoplasm in CRS group were common in hippocampus. However, the distribution of cofilin1 in mPFC was reversed. Pearson's correlation analysis revealed that there was a significant positive correlation found between the sucrose consumption in sucrose preference test and the dendrite density in multiple sub-regions of hippocampus and mPFC, and a significant negative correlation between the immobility time in tail suspension test and the dendrite/dendritic spine density in several different areas of hippocampus and mPFC. P-cofilin1 was significantly positively correlated with the overall dendritic spine density in mPFC as well as with the overall dendrite density or BDNF in the hippocampus. Our results suggest that the BDNF/cofilin1 pathway, in which cofilin1 may be activated in a brain-specific manner, was involved in resveratrol's attenuating the dendrite and dendritic spine loss and behavioral abnormality.

12.
Med Mycol ; 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33485272

RESUMO

A striking feature of pathogenic Candida species is morphological plasticity that facilitates environmental adaptation and host infection. Candida auris is an emerging multidrug-resistant fungal pathogen first described in Japan in 2009. In this study, we demonstrate that clinical isolates of C. auris have multiple colony and cellular morphologies including the yeast, filamentous, aggregated, and elongated forms. This phenotypic diversity has been observed in eight clinical isolates of C. auris representing four major genetic clades, suggesting that it could be a general characteristic. We further demonstrate that different cell types of C. auris exhibit distinct antifungal resistance and virulence properties in a Galleria mellonella infection model. Our findings imply that morphological diversity is an important biological feature of C. auris and could be a contributor to its emergence and rapid prevalence worldwide. LAY SUMMARY: Candida auris is an emerging multidrug-resistant fungal pathogen. Morphological analyses indicate that filamentation is a general feature of clinical isolates of C. auris. This ability is associated with antifungal resistance and virulence.

13.
J Clin Lab Anal ; 35(2): e23646, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33320365

RESUMO

OBJECTIVE: Tissue engineering has been a topic of extensive research in recent years and has been applied to the regeneration and restoration of many organs including the larynx. Currently, research investigating tissue engineering of the larynx is either ongoing or in the preclinical trial stage. METHODS: A literature search was performed on the Advanced search field of PubMed using the keywords: "(laryncheal tissue engineering) AND (cartilage regeneration OR scaffolds OR stem cells OR biomolecules)." After applying the selection criteria, 65 articles were included in the study. RESULTS: The present review focuses on the rapidly expanding field of tissue-engineered larynx, which aims to provide stem cell-based scaffolds combined with biological active factors such as growth factors for larynx reconstruction and regeneration. The trend in recent studies is to use new techniques for scaffold construction, such as 3D printing, are developed. All of these strategies have been instrumental in guiding optimization of the tissue-engineered larynx, leading to a level of clinical induction beyond the in vivo animal experimental phase. CONCLUSIONS: This review summarizes the current progress and outlines the necessary basic components of regenerative laryngeal medicine in preclinical fields. Finally, it considers the design of scaffolds, support of growth factors, and cell therapies toward potential clinical application.

14.
IEEE Trans Image Process ; 30: 1514-1526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33360994

RESUMO

Food recognition has captured numerous research attention for its importance for health-related applications. The existing approaches mostly focus on the categorization of food according to dish names, while ignoring the underlying ingredient composition. In reality, two dishes with the same name do not necessarily share the exact list of ingredients. Therefore, the dishes under the same food category are not mandatorily equal in nutrition content. Nevertheless, due to limited datasets available with ingredient labels, the problem of ingredient recognition is often overlooked. Furthermore, as the number of ingredients is expected to be much less than the number of food categories, ingredient recognition is more tractable in the real-world scenario. This paper provides an insightful analysis of three compelling issues in ingredient recognition. These issues involve recognition in either image-level or region level, pooling in either single or multiple image scales, learning in either single or multi-task manner. The analysis is conducted on a large food dataset, Vireo Food-251, contributed by this paper. The dataset is composed of 169,673 images with 251 popular Chinese food and 406 ingredients. The dataset includes adequate challenges in scale and complexity to reveal the limit of the current approaches in ingredient recognition.

15.
Entropy (Basel) ; 22(1)2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33285870

RESUMO

In this paper, a Blockchain-driven platform for supply chain finance, BCautoSCF (Zhi-lian-che-rong in Chinese), is introduced. It is successfully established as a reliable and efficient financing platform for the auto retail industry. Due to the Blockchain built-in trust mechanism, participants in the supply chain (SC) networks work extensively and transparently to run a reliable, convenient, and traceable business. Likewise, the traditional supply chain finance (SCF), partial automation of SCF workflows with fewer human errors and disruptions was achieved through smart contract in BCautoSCF. Such open and secure features suggest the feasibility of BCautoSCF in SCF. As the first Blockchain-driven SCF application for the auto retail industry in China, our contribution lies in studying these pain points existing in traditional SCF and proposing a novel Blockchain-driven design to reshape the business logic of SCF to develop an efficient and reliable financing platform for small and medium enterprises (SMEs) in the auto retail industry to decrease the cost of financing and speed up the cash flows. Currently, there are over 600 active enterprise users that adopt BCautoSCF to run their financing business. Up to October 2019, the BCautoSCF provides services to 449 online/offline auto retailors, three B2B asset exchange platforms, nine fund providers, and 78 logistic services across 21 provinces in China. There are 3296 financing transactions successfully completed in BCautoSCF, and the amount of financing is ¥566,784,802.18. In the future, we will work towards supporting a full automation of SCF workflow by smart contracts, so that the efficiency of transaction will be further improved.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33326203

RESUMO

Covalent triazine frameworks (CTFs) are promising electrodes for rechargeable batteries due to their adjustable structures, rich redox sites, and tunable porosity. However, the CTFs usually exhibit inferior electrochemical stability because of the inactivation of the unstable radical intermediates. Here, a methylene-linked CTF has been synthesized and evaluated as a cathode for rechargeable lithium-ion batteries. Electron paramagnetic resonance (EPR) and in situ Raman characterizations demonstrated that the redox activity and reversibility of α-C and triazine radical intermediates are essentially important for the charging/discharging process, which have been efficiently stabilized by the synergetic π conjugation and hindrance effect caused by the adjacent rigid triazine rings and benzene rings in the unique CTF-p framework. Additionally, the methylene groups provided extra redox-active sites. As a result, high capacity and cycling stability were achieved. This work inspires the rational modulation of the radical intermediates to enhance the electrochemical performance of organic electrode materials for the next-generation energy storage devices.

17.
Int J Chron Obstruct Pulmon Dis ; 15: 3213-3225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33311978

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is the third cause of disease-related death and brings a heavy burden to human health. Long non-coding RNA (lncRNA) was revealed to participate in COPD pathogenesis. This study aims to establish the effects and regulatory mechanism of lncRNA long intergenic non-coding 00987 (LINC00987) in lipopolysaccharide (LPS)-induced apoptosis, oxidative stress, inflammation and autophagy in BEAS-2B cells. Methods: The expression levels of LINC00987 and let-7b-5p were detected by real-time quantitativepolymerase chain reaction (RT-qPCR). The expression of apoptosis-associated proteins, oxidative stress (ROS)-related proteins, autophagy-related proteins and sirtuin1 (SIRT1) protein was determined by Western blot. Cell viability was illustrated by cell counting kit-8 (CCK-8) assay. Cell apoptosis was investigated by caspase3 activity and apoptosis analysis assays. ROS, inflammation and autophagy were demonstrated by detecting reactive ROS level and superoxide dismutase (SOD) activity, enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. The binding sites between let-7b-5p and LINC00987 or SIRT1 were predicted by lncBase or miRWalk online database, and identified by dual-luciferase reporter assay. Results: LINC00987 expression was strikingly downregulated and let-7b-5p expression was obviously upregulated in COPD tissues and LPS-induced BEAS-2B cells compared with control groups. LINC00987 overexpression promoted BEAS-2B cells against LPS-mediated viability, apoptosis, oxidative stress, inflammation and autophagy, whereas these effects were attenuated by let-7b-5p mimic or SIRT1 knockdown. Furthermore, LINC00987 sponged let-7b-5p and let-7b-5p bound to SIRT1. Conclusion: LINC00987 ameliorated COPD through modulating LPS-induced cell apoptosis, oxidative stress, inflammation and autophagy via sponging let-7b-5p to associate with SIRT1. This finding will provide a theoretical basis for the research of LncRNA-mediated treatment in COPD.

18.
PLoS Genet ; 16(12): e1008911, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33332348

RESUMO

Ploidy is the number of whole sets of chromosomes in a species. Ploidy is typically a stable cellular feature that is critical for survival. Polyploidization is a route recognized to increase gene dosage, improve fitness under stressful conditions and promote evolutionary diversity. However, the mechanism of regulation and maintenance of ploidy is not well characterized. Here, we examine the spontaneous diploidization associated with mutations in components of the Saccharomyces cerevisiae centrosome, known as the spindle pole body (SPB). Although SPB mutants are associated with defects in spindle formation, we show that two copies of the mutant in a haploid yeast favors diploidization in some cases, leading us to speculate that the increased gene dosage in diploids 'rescues' SPB duplication defects, allowing cells to successfully propagate with a stable diploid karyotype. This copy number-based rescue is linked to SPB scaling: certain SPB subcomplexes do not scale or only minimally scale with ploidy. We hypothesize that lesions in structures with incompatible allometries such as the centrosome may drive changes such as whole genome duplication, which have shaped the evolutionary landscape of many eukaryotes.


Assuntos
Centrômero/genética , Cromossomos Fúngicos/genética , Diploide , Dosagem de Genes , Centrômero/metabolismo , Cromossomos Fúngicos/metabolismo , Saccharomyces cerevisiae , Corpos Polares do Fuso/genética , Corpos Polares do Fuso/metabolismo
19.
PLoS One ; 15(11): e0241317, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33232332

RESUMO

Plant grafting is a sequential wound healing process. However, whether wounding induces a different jasmonic acid (JA) response within half a day (12 h) after grafting or non-grafting remains unclear. Using the tomato hypocotyl grafting method, we show that grafting alleviates the asymmetrical accumulation of JA and jasmonic acid isoleucine conjugate (JA-Ile) in scion and rootstock caused by wounding, and from 2 h after tomato micrografting, grafting obviously restored the level of JA-Ile in the scion and rootstock. Meanwhile, five JA-related genes, SlLOX11, SlAOS, SlCOI1, SlLAPA and SlJA2L, are detected and show significant changes in transcriptional expression patterns within 12 h of grafting, from asymmetrical to symmetrical, when the expression of 30 JA- and defense-related genes were analyzed. The results indicated that grafting alleviates the asymmetrical JA and defense response between scion and rootstock of the tomato hypocotyl within 12 h as induced by wounding. Moreover, we demonstrate that in the very early hours after grafting, JA-related genes may be involved in a molecular mechanism that changes asymmetrical expression as induced by wounding between scion and rootstock, thereby promoting wound healing and grafting success.

20.
Contemp Clin Trials ; 100: 106226, 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33238200

RESUMO

Missing data is common in clinical trials. Depending on the volume and nature of missing data, it may reduce statistical power for detecting treatment difference, introduce potential bias and invalidate conclusions. Non-responder imputation (NRI), where patients with missing information to determine endpoint status are considered as treatment failures, is widely used to handle missing data for dichotomous efficacy endpoints in inflammatory bowel disease (IBD) trials. However, it does not consider the mechanisms leading to missing data and can potentially underestimate the treatment effect. We proposed a hybrid imputation approach combining NRI and multiple imputation (MI) as an alternative to NRI to assess the impact of dropouts for different missing data mechanisms (categorized as "missing not at random [MNAR]" and "missing at random [MAR]"). Two phase 3 vedolizumab clinical trials under different study designs in patients with moderate-to-severe ulcerative colitis (UC), VISIBLE 1 and VARSITY, are presented to illustrate how the proposed hybrid approach can be implemented as a pre-specified sensitivity analysis in practice. The proposed hybrid imputation provided consistent efficacy results with those using NRI, and can serve as a useful pre-specified sensitivity analysis to assess the impact of dropouts under different missing data mechanisms and evaluate the robustness of efficacy conclusions.

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