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1.
BMC Geriatr ; 20(1): 32, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005155

RESUMO

BACKGROUND: In the age of aging, Korea's current medical delivery system threatens to increase the number of medical and caring refugees. This study attempts to develop an integrated senior citizen-oriented healthcare service system in which daily care, professional care, and rehabilitation are organically organized between medical institutions and local communities, thereby meeting the daily life needs of the elderly and inducing well-being, wellness, and well-dying. METHODS: To develop the integrated healthcare system, data collection and analyses were conducted through a systematic review, literature review, benchmarking, focus group interviews, and expert consultation. RESULTS: The senior-specific, citizen-oriented healthcare service system developed in this study is designed to screen patients aged 65 or older within 24 h of being admitted, using the Geriatric Screening for Care-10. If there is reason for concern as a result of the screening, further evaluation is performed through assessment. Doctors and nurses create a care plan and a discharge plan based on the results from the screening and assessment. The nurse further uses the screening to monitor the patient's condition before discharge. Based on the screening results at the time of discharge, a transitional care plan is prepared and provided to elderly patients and/or their families. This process enables a systematic link between medical institutions and community resources, aiming for the continuous management of health issues. It also establishes a multidisciplinary treatment plan that considers patients and their families so that diseases common to the elderly are diagnosed and treated promptly. CONCLUSIONS: The most important issue for the elderly is to be able to live healthily and independently for the rest of their lives through well-being, wellness, and well-dying. The senior-specific, citizen-oriented healthcare service proposed in this study is an integrated medical treatment system for elderly users the implementation of which requires the daily care, professional care, and rehabilitation of elderly members of society to be organically organized according to the role of the patients, their families, and the caregiver.

2.
J Prev Med Public Health ; 53(1): 15-25, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32023670

RESUMO

OBJECTIVES: The purpose of this study was to investigate the health effects of air conditioning use during the 2018 heat wave in Korea, included the highest temperature ever recorded in the nation. METHODS: The participants in this study were 1000 adults aged 19 years and older recruited from across Korea. The participants were asked about their experience of symptoms of various diseases, disruptions of their daily lives, and use of air conditioning during the heat wave. The associations between air conditioning use during the heat wave and health outcomes were analyzed using the chi-square test and multiple logistic regression models. RESULTS: Among participants who lacked air conditioning in the main space where they spent time outside the home, 33.9%, 8.1%, 43.5%, and 19.4% experienced symptoms of heat-related, cardiovascular, nervous system diseases, and air-conditioningitis, respectively. In comparison, participants who did have air conditioning outside the home experienced the same symptoms at proportions of 21.0%, 1.9%, 26.8%, and 34.2%, respectively (p=0.027, 0.007, 0.007, and 0.023, respectively). Among participants who had no air conditioner at home, 10.0% were absent from school or work due to the heat wave. In contrast, among participants who had an air conditioner at home, only 3.7% were absent as a result of the heat wave (p=0.007). CONCLUSIONS: When air conditioning was not used at home or in the main space where participants spent time outside the home during the 2018 heat wave, adverse health effects were more prevalent, but the risk of air-conditioningitis was reduced.

3.
Nat Commun ; 11(1): 877, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054837

RESUMO

Epstein-Barr virus (EBV) genomes persist in latently infected cells as extrachromosomal episomes that attach to host chromosomes through the tethering functions of EBNA1, a viral encoded sequence-specific DNA binding protein. Here we employ circular chromosome conformation capture (4C) analysis to identify genome-wide associations between EBV episomes and host chromosomes. We find that EBV episomes in Burkitt's lymphoma cells preferentially associate with cellular genomic sites containing EBNA1 binding sites enriched with B-cell factors EBF1 and RBP-jK, the repressive histone mark H3K9me3, and AT-rich flanking sequence. These attachment sites correspond to transcriptionally silenced genes with GO enrichment for neuronal function and protein kinase A pathways. Depletion of EBNA1 leads to a transcriptional de-repression of silenced genes and reduction in H3K9me3. EBV attachment sites in lymphoblastoid cells with different latency type show different correlations, suggesting that host chromosome attachment sites are functionally linked to latency type gene expression programs.

4.
Cancer Res Treat ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32019282

RESUMO

Myeloproliferative neoplasms (MPNs) are classified as chronic myeloid leukemia (CML) and Philadelphia chromosome-negative MPN. In MPN cases, the presence of a BCR-ABL1 translocation with a coexisting mutation is exceptionally rare. Herein, we report the first documented patient with CML harboring CALR mutation in Korea. A 33-year-old woman was referred to our hospital in February 2015 with splenomegaly, leukocytosis, and thrombocytosis. She was diagnosed with CML and started receiving nilotinib. In October 2015, a major molecular response was observed, but thrombocytosis persisted. A repeat bone marrow (BM) examination revealed no specific findings. However, as thrombocytosis worsened, we changed nilotinib to dasatinib. In May 2019, owing to persistent thrombocytosis, we repeated the BM examination and found CALR mutation (15.97%) on the MPN-next generation sequencing (NGS) test. We then retrospectively performed repeat MPN-NGS testing using the BM aspirate sample obtained in 2015 and found CALR mutation (10.64%).

5.
J Neurotrauma ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031040

RESUMO

Traumatic spinal cord injury (SCI) can cause permanent disabilities that seriously reduce quality of life. We evaluated the effects of chronic hyperglycemia before SCI on inflammatory markers and functional recovery after SCI in human patients and a rat model. In the human study, multivariate logistic regression analysis revealed that hemoglobin A1c (HbA1c) values, reflecting average plasma glucose concentration over a 3-month period, at admission were a significant risk factor for poor functional recovery. Moreover, patients with chronic hyperglycemia (HbA1c ≥ 6.5%) had high concentrations of inflammatory biomarkers (IL-6 and IL-8) of cerebrospinal fluid after SCI. Consistent with patient findings, chronic hyperglycemia before SCI in rats was associated with increased inflammatory responses and oxygen-free radicals in the spinal cord and blood, thus resulting in poor functional recovery and histologic outcomes. Tight glucose control before SCI decreased the harmful effects of hyperglycemia after SCI. Our findings suggest that chronic hyperglycemia before SCI may be a significant prognostic factor with a negative impact on functional and histologic outcomes, highlighting the importance of tight glucose control before SCI.

6.
Korean J Ophthalmol ; 34(1): 67-75, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32037751

RESUMO

PURPOSE: To investigate prognostic factors related to the surgical outcome of vitrectomy in myopic traction maculopathy (MTM). METHODS: Medical records of patients with MTM who underwent pars plana vitrectomy with internal limiting membrane peeling and follow-up over 12 months were reviewed retrospectively. Best-corrected visual acuity (BCVA), fundoscopic examination and spectral-domain optical coherence tomography findings were evaluated postoperatively. Functional success was defined as visual acuity gain and anatomical success was defined as reduction or resolution of foveoschisis without complications. RESULTS: This study included 40 eyes of 36 patients. BCVA improved from 0.70 ± 0.44 to 0.63 ± 0.57 logarithm of minimum angle of resolution and central macular thickness decreased from 526.6 ± 132.1 to 277.8 ± 92.1 µm at final follow-up. Functional success was achieved in 24 (60.0%) eyes, and 33 (82.5%) eyes reached anatomical success. Presence of foveal detachment (FD) and higher category of myopic maculopathy were associated with both functional (p = 0.014, 0.021, respectively) and anatomical (p = 0.011, 0.022, respectively) failure. Longer preoperative axial length showed an association with functional failure but not with anatomical failure (p = 0.041). In multivariate analysis, FD was the only prognostic factor for both functional and anatomical outcome (p = 0.041, 0.043, respectively). Preoperative BCVA (r² = 0.259, p = 0.001), axial length (r² = 0.172, p = 0.008), and myopic maculopathy category (r² = 0.336, p < 0.001) showed significant correlation with final BCVA. CONCLUSIONS: More severe myopic maculopathy and the presence of FD are associated with poorer functional and anatomical outcomes of pars plana vitrectomy in MTM. Better preoperative BCVA, shorter axial length, and less severe myopic maculopathy are correlated with better final BCVA.

7.
Chem Commun (Camb) ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31971182

RESUMO

The intrinsic l-DNA binding properties of a natural DNA polymerase was discovered. The binding affinity of Dpo4 polymerase for l-DNA was comparable to that for d-DNA. The crystal structure of Dpo4/l-DNA complex revealed a dimer formed by the little finger domain that provides a binding site for l-DNA.

8.
Biomater Sci ; 8(2): 586-590, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31913375

RESUMO

While siRNA is a potent therapeutic tool that can silence disease-causing mRNA, its in vivo potency can be compromised due to the lack of target tissue specificity. Here, we report a wireframe tetrahedral DNA nanostructure having a 20-mer duplex on each side that can be specifically distributed into the liver upon systemic administration. This liver-targeted DNA tetrahedron is employed as the carrier for liver-specific delivery of siRNA targeting ApoB1 mRNA, which is overexpressed in hypercholesterolemia. When delivered by a DNA tetrahedron, the siRNA can preferentially be accumulated in the liver and down-regulate the ApoB1 protein. As a result, the blood cholesterol level is also decreased by the siRNA. These results successfully demonstrate that the DNA tetrahedron is a promising carrier for liver-targeted delivery of therapeutic nucleic acids.

9.
Acc Chem Res ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31920073

RESUMO

Block copolymers (BCPs) have been indispensable building blocks to create a range of soft nanostructures including discrete particulates (micelles and vesicles) and periodic structures via spontaneous assembly in bulk and in solution. The size, shape, and phase of these structures can be controlled by the rational design of the molecular structure of building blocks based on the structural analogy of BCPs to lipids and small molecule surfactants. Inverse bicontinuous cubic mesophases of polymers, or polymer cubosomes when in colloidal forms, are emerging nanostructures composed of triply periodic minimal surfaces (TPMSs) of block copolymer bilayers. Created by spontaneous assembly of BCPs in solution, polymer cubosomes internalize two nonintersecting nanochannel networks arranged in a cubic crystalline order. As well-defined porous particles with highly ordered internal structures and high surface-area-to-volume ratios, polymer cubosomes can be used for chemical reactors or bioreactors, carriers capable of cargo loading and release, and scaffolds for nanotemplating. However, despite their structural similarity to lipid cubosomes and applicability, polymer cubosomes have been only sporadically observed as an outcome of serendipity until recent studies demonstrated that BCPs could form well-defined polymer cubosomes in solution. In this Account, we describe our recent progress in creating polymer cubic mesophases and their colloidal particles (polymer cubosomes) in dilute solution. BCPs with nonlinear architectures (dendritic-linear, branched-linear, and branched-branched BCPs) preferentially self-assembled to inverse mesophases in solution when the block ratio (f), defined as a molecular weight ratio of the hydrophilic block to that of the hydrophobic block, was small (<10%). The resulting lyotropic structures transformed from flat bilayers to cubic phases of primitive cubic and double diamond lattices and finally to inverted hexagonal phases as f decreased. We proposed that the architecture of a BCP plays an important role in the preferential formation of polymer cubosomes in solution. The presence of the bulky hydrophilic block limited chain stretching of the hydrophobic polymer block, which would increase the packing parameter of the BCP to greater than unity, a prerequisite for inverse mesophase formation. The structural characteristics of polymer cubosomes, such as lattice symmetries, pore sizes, and lattice parameters, could also be controlled by fine-tuning the structural parameters of BCPs. We also suggested nonsynthetic methods to precisely control the phase and internal lattice of inverse mesophases of BCPs by the coassembly of two BCPs with different block ratios (mix-and-match approach) and the modulation of the affinity of the common solvent toward the hydrophobic block of the BCP. To investigate the potential applications of polymer cubosomes, we prepared inorganic photonic crystals using a cubosome-templated synthesis. We also discussed the utilization of cubosomes as chemical reactors by functionalization of the surface and the covalent stabilization of transient self-assembled structures via cross-linking of the hydrophobic domain. This Account reflects the efforts of synthetic chemists to understand the self-assembly behavior of BCPs to form complex morphologies in solution. We hope that our Account inspires efforts from chemists and other scientists to further understand these structures with infinite mazes of complexity and possibility.

10.
J Clin Neurosci ; 72: 124-129, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31948880

RESUMO

OBJECTIVE: Full-endoscopic lumbar discectomy (FELD) is a minimally invasive surgical option for recurrent lumbar disc herniation (LDH). Nonetheless, patients' clinical outcomes may be poorer after surgery for recurrent LDH than for primary LDH. Therefore, we compared patients' longitudinal clinical outcomes after FELD for recurrent LDH or primary LDH. METHODS: The medical records of patients who underwent FELD for primary LDH (group A) or recurrent LDH (group B) were retrospectively reviewed. The inclusion criteria were: 1) single-level LDH or recurrent LDH at L4-5 or L5-S1, 2) age ≤60 years, 3) previous open discectomy (group B), and 4) ≥6 months of follow-up. In total, 244 patients (group A, 211; group B, 33) were included. Clinical outcomes (Oswestry Disability Index [ODI]; visual analogue pain score for the back and leg [VAS-B] and [VAS-L]) over 24 months of follow-up were compared between groups with a linear mixed-effects model. RESULTS: All clinical outcomes significantly improved from pre-operation to 3 months postoperatively (p < 0.01), and the improvement was maintained for 24 months postoperatively in both groups. The clinical outcomes of groups A and B were not significantly different during 24 months follow-up (ODI, p = 0.94; VAS-B, p = 0.11; and VAS-L, p = 0.48). The reoperation rate was 3.3% in group A and 3.0% in group B, but the overall complication rate was higher in group B (9.8%) than in group A (6.6%). CONCLUSION: The longitudinal clinical outcomes after FELD for recurrent LDH may not be poor as feared. However, the higher complication rate in patients undergoing FELD for recurrent LDH should be noted.

11.
J Periodontol ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31961450

RESUMO

BACKGROUND: The aim of this study was to seek the critical time for impairment of alveolar bone regeneration after ovariectomy (OVX) in rats. METHODS: A total of 32 female rats were used. Test group rats were divided into a 2M group (n = 8), a 3M group (n = 8) and a 4M group (n = 8) according to the duration from OVX to defect creation. Bilateral OVX was performed in all test groups, and a sham operation was performed in the control group (n = 8). Drill-hole defects (1.5 mm diameter, 2 mm length) were created on both sides of the maxilla. All rats were euthanized 2 and 4 weeks after the surgery. Microcomputed tomographic (micro-CT), histological, and histomorphometric analyses and in vitro experiments were performed. RESULTS: The 4M group showed significantly less new bone formation and a lower bone mineral density than the other groups in the micro-CT analysis. The histomorphometric analysis also revealed that the 4M group showed significantly less new bone formation than the control and 2M groups. The rats in the 4M group showed significantly higher alkaline phosphatase expression levels and a larger number of calcified nodules than rats in the other groups, whereas osteoclastic activity was significantly lower in the 4M group than in the other groups. CONCLUSIONS: The critical time for impairment of alveolar bone regeneration was 4 months after OVX in rats.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31958303

RESUMO

OBJECTIVE: To compare the efficacy and safety of an initial triple therapy using metformin, a dipeptidyl peptidase-4 (DPP4) inhibitor, and thiazolidinedione with a stepwise approach using sulfonylurea and metformin in new-onset, drug-naïve patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Among drug-naïve patients with 9.0%-12.0% glycated hemoglobin (HbA1c) but no hyperglycemic symptoms, 100 subjects who started triple medications (metformin 1000 mg/day, sitagliptin 100 mg/day, and lobeglitazone 0.5 mg/day) were selected as an initial triple therapy group. Age and body mass index-matched subjects (n=100) who started glimepiride (≥2 mg/day with uptitration) and metformin (≥1000 mg/day with uptitration) were selected as a conventional therapy group. We investigated changes in HbA1c level, dynamic indexes for insulin sensitivity and ß-cell function, and hypoglycemia. RESULTS: After 12 months of treatment, HbA1c levels decreased significantly in both groups: from 10.7%±1.0% to 6.7%±1.3% in the triple group, and from 10.5%±1.0% to 7.3%±1.2% in the conventional therapy group. At 12 months, achievement of the HbA1c target (<7.0%) was higher in the triple group than in the conventional group (70% vs 52%, p<0.01). Dynamic indexes related to ß-cell function and insulin sensitivity improved, and albuminuria reduced significantly only in the triple group. Hypoglycemia was more common in the conventional group. CONCLUSIONS: Initial triple combination therapy with the DPP4 inhibitor, metformin, and thiazolidinedione showed a higher achievement of the target HbA1c goal with a lower risk of hypoglycemia, better restoration of ß-cell function, and multiple metabolic benefits, implying durable glycemic control. This strategy may be useful for patients presenting with type 2 diabetes and high HbA1c levels.

13.
PLoS One ; 15(1): e0228114, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31968016

RESUMO

Genome-wide association studies (GWAS) have enabled the discovery of candidate markers that play significant roles in various complex traits in plants. Recently, with increased interest in the search for candidate markers, studies on epistatic interactions between single nucleotide polymorphism (SNP) markers have also increased, thus enabling the identification of more candidate markers along with GWAS on single-variant-additive-effect. Here, we focused on the identification of candidate markers associated with flowering time in soybean (Glycine max). A large population of 2,662 cultivated soybean accessions was genotyped using the 180k Axiom® SoyaSNP array, and the genomic architecture of these accessions was investigated to confirm the population structure. Then, GWAS was conducted to evaluate the association between SNP markers and flowering time. A total of 93 significant SNP markers were detected within 59 significant genes, including E1 and E3, which are the main determinants of flowering time. Based on the GWAS results, multilocus epistatic interactions were examined between the significant and non-significant SNP markers. Two significant and 16 non-significant SNP markers were discovered as candidate markers affecting flowering time via interactions with each other. These 18 candidate SNP markers mapped to 18 candidate genes including E1 and E3, and the 18 candidate genes were involved in six major flowering pathways. Although further biological validation is needed, our results provide additional information on the existing flowering time markers and present another option to marker-assisted breeding programs for regulating flowering time of soybean.

14.
PLoS One ; 15(1): e0228150, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978110

RESUMO

Many studies have found associations between unicompartmental knee arthroplasty (UKA) and implant survival, but controversy still exists regarding the relative survival of medial versus lateral UKA over mid-to long-term follow-up. The purpose of this study was to compare survival and clinical outcomes of medial and lateral UKAs. In this meta-analysis, we reviewed studies that assessed implant survival in patients who underwent medial or lateral UKA with short- to mid-term (<10years) or long-term (>10years) follow-up, and that used assessments, such as pain and function scores, to compare postoperative scores on knee outcome scales. A total of eight studies (33,999 knees with medial UKA and 2,853 with lateral UKA) met the inclusion criteria and was analyzed in detail. There were no significant differences between medial and lateral UKA in pain score (95% CI: -0.37 to 0.88; P = 0.42), function score (95% CI: -0.19 to 0.60; P = 0.31), short- to mid-term survival (medial, 32,083/33,483; lateral, 2,636/2,726; OR 0.98, 95% CI: 0.64 to 1.48;P = 0.91), or long-term survival (medial, 479/516; lateral, 110/127; OR 2.51, 95% CI:0.67 to 9.43; P = 0.17). In addition, both groups had substantial proportions of knees with short- to mid-term survival (95.6% by medial UKA and 94.6% by lateral UKA) and long-term survival (92.8% by medial UKA and 86.6% by lateral UKA). This meta-analysis found no significant differences in short- to mid-term and long-term survival of medial and lateral UKAs. Similarly, patients treated with medial UKA showed no difference in pain relief or functional improvement compared to patients treated with lateral UKA. These results suggest that both UKA techniques are viable treatment options for patients with unicompartmental knee osteoarthritis over long-term follow-up, although further high-quality studies are needed to address some remaining uncertainties regarding the clinical benefits of these procedures.

15.
Mod Pathol ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953522

RESUMO

Comprehensive molecular analyses revealed that papillary renal cell carcinoma (PRCC) is a heterogenous entity. Papillary renal neoplasm with reverse polarity (PRNRP) is a subset of PRCC with characteristic histomorphologies such as low-grade nuclear features, inverted nuclear location, eosinophilic cytoplasm, and indolent clinical behavior. We tried to define the molecular, clinicopathological, histologic, and immunohistochemical features of PRNRP by comparing them with type 1 PRCC (PRCC1) and type 2 PRCC (PRCC2). A cohort of 30 PRNRP, 23 PRCC1, and 26 PRCC2 cases was used. Targeted sequencing of 90 cancer-related genes including KRAS was performed in 26 PRNRP tumor samples. PNA-mediated clamping PCR of KRAS was performed using paired normal and tumor DNA from 30 PRNRP, 23 PRCC1, and 26 PRCC2 cases. Tissue microarray slides were made in three cores per tumor, which were stained with cytokeratin 7 (CK7), alpha-methylacyl-CoA racemase (AMACR), epithelial membrane antigen (EMA), E-cadherin, vimentin, and CD10. Recurrent mutations in KRAS were detected in 28 of the 30 PRNRPs. However, there were no KRAS mutations in any PRCC1 or PRCC2 cases. PRNRP exhibited distinct clinicopathological features: small tumor size, lower pathologic T stage, and no disease-specific death during the follow-up period. Histologically, peritumoral lymphoid aggregation, prominent papillary architecture (>80% of tumor), hyalinized papillae, inverted nuclear location, and lower nuclear grade were observed. PRNRP was usually positive for CK7, AMACR, EMA, and E-cadherin, and negative for CD10. The findings suggest that PRNRP is a subtype of papillary renal neoplasm that is different from PRCC1 or PRCC2 in terms of molecular, clinicopathological, histological, and immunohistochemical features.

16.
PLoS One ; 15(1): e0227430, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31914142

RESUMO

In this study, we propose a method to quantitatively analyze the concentration of VOCs adsorbed on zeolite filters via gas chromatography (GC). The sampled VOCs from the filters with ethanol as a solution were characterized using GC to determine the concentration of the adsorbed VOCs by comparing the areas of GC peaks of the detected VOCs and ethanol. The proposed method also enabled determination of the desorption (regeneration) conditions of the zeolite filters according to heating temperature and time for various VOCs. Repeated adsorption and desorption of VOCs on zeolite filters and GC analyses allow us to evaluate the durability and reusability of the filter and could help predict the lifetime of zeolite filters in practice.

17.
Nat Commun ; 11(1): 56, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911612

RESUMO

Synthesis of a polymer composed of a large discrete number of chemically distinct monomers in an absolutely defined aperiodic sequence remains a challenge in polymer chemistry. The synthesis has largely been limited to oligomers having a limited number of repeating units due to the difficulties associated with the step-by-step addition of individual monomers to achieve high molecular weights. Here we report the copolymers of α-hydroxy acids, poly(phenyllactic-co-lactic acid) (PcL) built via the cross-convergent method from four dyads of monomers as constituent units. Our proposed method allows scalable synthesis of sequence-defined PcL in a minimal number of coupling steps from reagents in stoichiometric amounts. Digital information can be stored in an aperiodic sequence of PcL, which can be fully retrieved as binary code by mass spectrometry sequencing. The information storage density (bit/Da) of PcL is 50% higher than DNA, and the storage capacity of PcL can also be increased by adjusting the molecular weight (~38 kDa).

18.
Artigo em Inglês | MEDLINE | ID: mdl-31924614

RESUMO

Vibrio sp. EJY3 is an agarolytic marine bacterium that catabolizes 3,6-anhydro-l-galactose (AHG), a monomeric sugar unit of agarose. While the AHG catabolic pathway in EJY3 has been recently discovered, the complete agarolytic system of EJY3 remains unclear. We have identified five enzymes, namely the ß-agarases VejGH50A, VejGH50B, VejGH50C, and VejGH50D and the α-neoagarooligosaccharide (NAOS) hydrolase VejGH117, involved in the agarolytic system of EJY3. Based on the characterization of recombinant enzymes and intracellular metabolite analysis, we found that EJY3 catabolizes agarose via two different agarolytic pathways. Among the four EJY3 ß-agarases, VejGH50A, VejGH50B, and VejGH50C, were found to be extracellular agarases, producing mainly neoagarotetraose (NeoDP4) and neoagarobiose. By detecting intracellular NeoDP4 in EJY3 grown on agarose, NeoDP4 was observed being taken up by cells. Intriguingly, intracellular NeoDP4 acted as a branching point for the two different downstream agarolytic pathways. First, via the well-known agarolytic pathway, NeoDP4 was depolymerized into monomeric sugars by the exo-type ß-agarase, VejGH50D and α-NAOS hydrolase, VejGH117. Second, via the newly found alternative agarolytic pathway, NeoDP4 was depolymerized into AHG and agarotriose (AgaDP3) by VejGH117, and AgaDP3 was then completely depolymerized into monomeric sugars by sequential enzymatic reactions of the agarolytic ß-galactosidase (ABG), VejABG and VejGH117. Therefore, by experimentally verifying agarolytic enzymatic activity and transport of NeoDP4 into EJY3 cells, we revealed that EJY3 possesses both the known pathway and a newly discovered alternative pathway that involves α-NAOS hydrolase and ABG.IMPORTANCE Agarose is the main polysaccharide of red macroalgae and is composed of galactose and 3,6-anhydro-l-galactose. Many marine bacteria possess enzymes capable of depolymerizing agarose into oligomers and then depolymerizing the oligomers into monomers. Here, we experimentally verified that both a well-known and a novel agarolytic pathway exist in a marine bacterium, Vibrio sp. EJY3. In agarolytic pathways, agarose is depolymerized mainly into 4-sugar-unit oligomers by extracellular enzymes, which are then transported into cells. The imported oligomers are intracellularly depolymerized into galactose and 3,6-anhydro-l-galactose by two different agarolytic pathways, using different combinations of intracellular enzymes. These results elucidate the depolymerization routes of red macroalgal biomass in the ocean by marine bacteria and provide clues for developing industrial processes for efficiently producing sugars from red macroalgae.

19.
Microbiologyopen ; : e992, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31925997

RESUMO

This study was conducted to investigate the long-term effect of a low fish meal (FM) diet comprising plant-based protein sources (PPS) on changes of gut microbial diversity in olive flounder (Paralichthys olivaceus) over the course of life. Two experimental diets were prepared to contain 74% FM (control) or 52% FM with 22% PPS (30% FM replacement, FM30). Fish were fed one of the two experimental diets for 8 months, and we collected the midgut contents to analyze the gut bacterial community by Illumina MiSeq based on the metagenomic sequences in the V3-V4 regions of 16S rRNA. We found that there were nine dominant phyla, which in turn presented Proteobacteria, Firmicutes, and Actinobacteria as the three major phyla in the gut microbiota of the flounder. At genus level, the dominant genera were Delftia, Prevotella, and Chthoniobacter at the juvenile stage (below 100 g/fish); Chthoniobacter, Bacillus, and Bradyrhizobium at the grower stage (400 g/fish); Chthoniobacter, Bacillus, and Delftia at the subadult stage (800 g/fish); and Lactobacillus and Prevotella at the adult stage (over 1,000 g/fish). The microbial diversity in olive flounders arched from the juvenile and subadult stage and reached a plateau thereafter. The fish fed the FM30 diet significantly had an increased abundance of Lactobacillus and Photobacterium and had less abundance of Prevotella and Paraprevotella than the control. However, the effect of dietary PPS was not significant on total microbial richness, indicating no negative effect as feed sources on the intestinal microbiota in olive flounder. These results indicate that the life stage of olive flounder is more important in modulating intestinal microbiota than is the diet. It could also be concluded that dietary PPS might be used as a potential fish meal alternative without any compromising effects on microbial diversity of olive flounder for long-term feeding.

20.
Curr Biol ; 30(2): 276-291.e9, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31928877

RESUMO

Current pharmacological treatments for Parkinson's disease (PD) are focused on symptomatic relief, but not on disease modification, based on the strong belief that PD is caused by irreversible dopaminergic neuronal death. Thus, the concept of the presence of dormant dopaminergic neurons and its possibility as the disease-modifying therapeutic target against PD have not been explored. Here we show that optogenetic activation of substantia nigra pars compacta (SNpc) neurons alleviates parkinsonism in acute PD animal models by recovering tyrosine hydroxylase (TH) from the TH-negative dormant dopaminergic neurons, some of which still express DOPA decarboxylase (DDC). The TH loss depends on reduced dopaminergic neuronal firing under aberrant tonic inhibition, which is attributed to excessive astrocytic GABA. Blocking the astrocytic GABA synthesis recapitulates the therapeutic effect of optogenetic activation. Consistently, SNpc of postmortem PD patients shows a significant population of TH-negative/DDC-positive dormant neurons surrounded by numerous GABA-positive astrocytes. We propose that disinhibiting dormant dopaminergic neurons by blocking excessive astrocytic GABA could be an effective therapeutic strategy against PD.

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