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1.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(7): 1266-1273, 2021 Jul 10.
Article in Chinese | MEDLINE | ID: mdl-34814542

ABSTRACT

Objective: To explore the genetic characteristics and evolution of hantavirus carried by rodents in port area of Ningde in Fujian province in the summer of 2020. Methods: Rodents were captured in the port area of Ningde, the RNA was extracted from rodent lung tissues and detected by using specific kit. The positive samples were used for whole-genome sequencing of the virus. Bioinformatics software was used for the analysis on the similarity and genetic variation of the sequences. Results: A total of 112 rodents were captured, including 5 Rattus norvegicus and 2 Rattus flavipectus, the positive rate of hantavirus was 6.25% (7/112). By virus gene sequencing, two hantavirus complete genome sequences were obtained (named as FJ35 and FJ36, GenBank accession numbers: MW449188-MW449193). The genetic analysis results showed that the hantavirus detected in positive samples were SEOV and shared 99% nucleotide similarity with hantavirus strains LZSF21 and JX20140581 isolated from Shandong province. Phylogenetic analysis using the maximum likelihood method showed that the hantavirus detected in positive samples belonged to S3 subtype, sharing the same subtype with hantavirus strains Z37 from Zhejiang province, LZSF21 from Shandong province, and zy27 and Gongzhuling 415 from northeastern China. Compared with FJ372, the amino acid variation of N259S was observed at sites 251-264 of nucleoprotein, which might be related to antigenicity. Another variation of Q81R was observed in glycoprotein compared with SEOV 80-39 segment of coded amino acid of international reference strain, which might also cause the change in antigenicity. Conclusion: The high positive rate of hantavirus in rodents in the port area of Ningde- would increase the risk of natural human infection and epidemic in local area. The hantavirus positive rodents in this focus might be from an endemic area in Shandong. It is necessary to strengthen the imported rodent control in the port area of Ningde. The virus detected in 2 positive samples belonged to SEOV subtype Ⅲ and shared high homologies of nucleotides and amino acid sequences with the hantavirus strains in surrounding area. However, some slight variations occurred in glycoprotein and nucleoprotein amino acid sequences, which might cause changes in its antigeniity.


Subject(s)
Hantavirus Infections , Orthohantavirus , Animals , China/epidemiology , Orthohantavirus/genetics , Hantavirus Infections/epidemiology , Phylogeny , RNA, Viral/genetics , Rats , Rodentia
2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(10): 1809-1816, 2021 Oct 10.
Article in Chinese | MEDLINE | ID: mdl-34814616

ABSTRACT

Objective: To identify age and gender standardized body mass index among children and adolescents and explore their associations with high blood pressure (HBP) in late adolescence. Methods: The current study was based on the Health Promotion Program for Children and Adolescents, school-based surveillance successively conducted from 2012 to 2019 in Suzhou, China. A total of 11 812 children and adolescents aged 16-18 years, who had ≥4 examination records during 2012-2018 and were also involved in a surveillance program in 2019, were included. Latent class growth mixture modeling was used to identify the BMI-Z trajectories in different genders, and multivariate logistic regression was used to analyze the associations between different BMI-Z trajectories and risk of HBP in late adolescence. Results: Six distinct BMI-Z trajectories were determined for both genders:thin, slightly thin,standard, declining, overweight, and obese. Compared with the regular group, the obesity group had 94.0% (OR=1.94, 95%CI: 1.43-2.63) and 107.0% (OR=2.07, 95%CI: 1.33-3.22) increased risk of developing HBP in late adolescence in boys and girls, respectively. However, a neutral association was found between the descending group and HBP in late adolescence. Conclusions: Persistent obesity in children may increase the risk of HBP in their late adolescence. If an obese child restores normal weight before late adolescence, the risk of HBP may reduce.


Subject(s)
Hypertension , Pediatric Obesity , Adolescent , Blood Pressure , Body Mass Index , Child , Female , Humans , Hypertension/epidemiology , Logistic Models , Male , Overweight , Pediatric Obesity/epidemiology
3.
Phys Rev Lett ; 125(5): 053001, 2020 Jul 31.
Article in English | MEDLINE | ID: mdl-32794882

ABSTRACT

We report the electromagnetically-induced-transparency (EIT) cooling of a large trapped ^{171}Yb^{+} ion chain to the quantum ground state. Unlike conventional EIT cooling, we engage a four-level tripod structure and achieve fast sub-Doppler cooling over all motional modes. We observe simultaneous ground-state cooling across the complete transverse mode spectrum of up to 40 ions, occupying a bandwidth of over 3 MHz. The cooling time is observed to be less than 300 µs, independent of the number of ions. Such efficient cooling across the entire spectrum is essential for high-fidelity quantum operations using trapped ion crystals for quantum simulators or quantum computers.

4.
Philos Trans A Math Phys Eng Sci ; 375(2108)2017 Dec 13.
Article in English | MEDLINE | ID: mdl-29084886

ABSTRACT

Linear arrays of trapped and laser-cooled atomic ions are a versatile platform for studying strongly interacting many-body quantum systems. Effective spins are encoded in long-lived electronic levels of each ion and made to interact through laser-mediated optical dipole forces. The advantages of experiments with cold trapped ions, including high spatio-temporal resolution, decoupling from the external environment and control over the system Hamiltonian, are used to measure quantum effects not always accessible in natural condensed matter samples. In this review, we highlight recent work using trapped ions to explore a variety of non-ergodic phenomena in long-range interacting spin models, effects that are heralded by the memory of out-of-equilibrium initial conditions. We observe long-lived memory in static magnetizations for quenched many-body localization and prethermalization, while memory is preserved in the periodic oscillations of a driven discrete time crystal state.This article is part of the themed issue 'Breakdown of ergodicity in quantum systems: from solids to synthetic matter'.

5.
Med J Malaysia ; 71(4): 161-165, 2016 08.
Article in English | MEDLINE | ID: mdl-27770113

ABSTRACT

INTRODUCTION: Jellyfish stings are the most frequently reported marine animal envenomation worldwide. However, data on jellyfish sting from Malaysia remains obscure due to inadequate research. METHODS: We investigated the epidemiology, clinical features and treatment of patients presenting at the emergency department of Langkawi Hospital between January 2012 and December 2014. Secondary data on the nature of the incident, patient demographics, clinical presentation, and treatment were retrieved from the patients' medical records. Descriptive statistics were presented for all patient variables. RESULTS: A total of 759 patients presented with jellyfish stings during the 3-year study period, with highest number of visits in July, October, November, and December. The mean patient age was 26.7 years (SD: 12.14), 59.4% were men, 68.1% were foreigners or international tourists, and 40.4% were stung between 12.00 p.m. and 6:59 p.m. At least 90 patients presented with mild Irukandji or Irukandji-like syndromes. Most of the jellyfish stings occurred at Chenang Beach (590 reported cases), followed by Tengah Beach and Kok Beach. Most patients were treated symptomatically, and no deaths following a jellyfish sting was reported during the study period. CONCLUSION: There is a need for public health interventions for both local and international tourists who visit Langkawi Island. Preventive steps and education on initial treatment at the incident site could elevate public awareness and decrease the adverse effects of jellyfish stings.


Subject(s)
Bites and Stings , Emergency Service, Hospital , Scyphozoa , Adolescent , Adult , Animals , Female , Humans , Malaysia , Male , Public Health , Syndrome , Young Adult
6.
Eur Rev Med Pharmacol Sci ; 20(13): 2842-52, 2016 07.
Article in English | MEDLINE | ID: mdl-27424984

ABSTRACT

OBJECTIVE: Pancreatic neuroendocrine tumors are relatively rare pancreatic neoplasms over the world. Investigations of the molecular biology of PNETs are insufficient for nowadays. We aimed to explore the expression of microRNA and messenger RNA and regulatory processes underlying pancreatic neuroendocrine tumors. MATERIALS AND METHODS: The messenger RNA and microRNA expression profile of GSE43796 were downloaded, including 6 samples with pancreatic neuroendocrine tumors and 5 healthy samples. First, the Limma package was utilized to distinguish the differentially expressed messenger RNA and microRNA separately. Then we used microRNA Walk databases to predict the target genes of the differentially expressed microRNAs (DE-microRNAs), and selected differentially expressed target genes whose expression was reversely correlated with microRNAs. Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to explore the functions and pathways of target genes. In addition, we constructed a regulatory miRNAs-target genes network and a protein-protein interaction network. RESULTS: There were 28 differentially expressed microRNAs and 859 differentially expressed messenger RNAs, including 253 potential target genes. These target genes mainly enriched in ABC transporters pathway. In this network, hsa-miR-7-2-3p demonstrated the highest connectivities whereas KLF12 was the mRNAs with the highest connectivities. CXCL12 was identified as the hub of the protein-protein interaction sub-network. CONCLUSIONS: The genes involved in ABC transporters and Type II diabetes mellitus pathway, KLF12 and CXCL12 may play an important role in the progression of pancreatic neuroendocrine tumors. However, more experimental studies are required.


Subject(s)
Carcinoma, Neuroendocrine/genetics , MicroRNAs/genetics , Neoplasm Proteins/metabolism , Pancreatic Neoplasms/genetics , RNA, Messenger , Carcinoma, Neuroendocrine/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Proteins/genetics , Pancreatic Neoplasms/metabolism , Protein Binding
7.
Med J Malaysia ; 70(5): 307-11, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26556121

ABSTRACT

BACKGROUND: Antibiotic resistance is a rising problem in Malaysia. For instance, high antibiotic prescribing rate for upper respiratory tract infection and inappropriate choice of antibiotic is a significant healthcare concern in Malaysia. Our main objective was to study knowledge, attitude and practice of antibiotic prescribing among medical officers in Kedah, Malaysia. METHODS: A cross sectional study was conducted in outpatient departments of health clinics and hospitals in Kedah from June 2013 until December 2013. Sample size was 118 and systematic sampling was conducted. Research tool used was a validated questionnaire from studies conducted in Congo and Peru. RESULTS: Response rate was 84.8%. Majority of our respondents were female doctors (71.0%), local graduates (63.0%), and practiced for 4 years or less (61.0%). 52.0% of the respondents prescribed antibiotics more than once daily. Mean knowledge score on antibiotics was 5.31 ±1.19 (95% CI: 5.06; 5.54). More than half (62.0%) of our respondents were confident in antibiotic prescribing and there were merely 18.0% of them consulted any colleagues prior to prescription. There was a significant difference in frequency of antibiotic prescribing between junior doctors and senior doctors (P-value: 0.036). In addition, there was also a significant association between frequency of antibiotic prescribing and awareness of antibiotic resistance in their daily practice. (P-value: 0.002). CONCLUSION: Knowledge on antibiotic was moderate among our medical officers and antibiotic prescribing was frequent. Training and courses on appropriate antibiotic prescribing should be emphasized to ensure the best practice in antibiotic prescription.

8.
Cell Mol Biol (Noisy-le-grand) ; 61(3): 79-83, 2015 Jul 31.
Article in English | MEDLINE | ID: mdl-26255135

ABSTRACT

HOTAIR, a long non—coding RNA (lncRNA), is reported to regulate chromatin organization and promote tumor progression. However, little is known about the roles of this gene in the modulation of calcium homeostasis in human cardiomyocytes. In the present study, we demonstrated that up—regulation of HOTAIR could suppress the expression of CaV1.2 in human cardiomyocytes. However, HOTAIR knockdown promoted CaV1.2 expression in human cardiomyocytes. In addition, we found that HOTAIR overexpression significantly reduced the intracellular Ca2+ contents; while knockdown of HOTAIR enhanced the Ca2+ contents in the cardiomyocytes. Moreover, enforced expression of CaV1.2 increased the calcium level in cardiomyocytes overexpressing HOTAIR. down—regulation of HOTAIR and up—regulation of CaV1.2 further enhanced the Ca2+ contents in the cardiomyocytes Taken together, these results for the first time demonstrate that HOTAIR inhibited the intracellular Ca2+ via regulation of CaV1.2 in human cardiomyocytes.


Subject(s)
Calcium Channels, L-Type/metabolism , Calcium/metabolism , RNA, Long Noncoding/metabolism , Calcium Channels, L-Type/chemistry , Cell Line , Humans , Microscopy, Fluorescence , Myocytes, Cardiac , RNA Interference , RNA, Long Noncoding/antagonists & inhibitors , RNA, Long Noncoding/genetics , RNA, Small Interfering/metabolism , Real-Time Polymerase Chain Reaction , Up-Regulation
9.
J Clin Pharm Ther ; 40(3): 266-72, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25865563

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: It has been reported that more than 80% of out-of-hospital medication errors among the young children involve liquid formulations. The usefulness of pictorial aids to improve communication of medication instructions has not been extensively investigated for child health. The objective of this study was to determine the effectiveness of pictorial aids used to assist caregivers in the administration of liquid medications. METHODS: MEDLINE, CINAHL, PsycINFO, ScienceDirect, Scopus and the Cochrane Library were searched for articles published up to February 2015. Studies that used pictorial aids with liquid medications and measured at least one of the following outcomes were included: dosing accuracy, comprehension of medication instructions, recall of information and adherence of caregivers. Two authors independently selected studies, extracted data and assessed methodological quality of studies using the Cochrane Collaboration's tool. RESULTS AND DISCUSSION: Five experimental studies (four hospital based and one community based) with a total of 962 participants were included. A wide range of liquid formulations were studied, including both prescription and over-the-counter medications. The existing findings suggest that pictographic interventions reduced dosing errors, enhanced comprehension and recall of medication instructions and improved adherence of caregivers. Incorporating pictorial aids into verbal medication counselling or text-based instructions was more beneficial than using the single approach alone. Mixed results were identified for the relationship between health literacy of caregivers and effectiveness of pictorial aids. WHAT IS NEW AND CONCLUSION: The evidence remains limited due to the small number of studies found and variations in methodological quality. This review suggests that pictorial aids might be potential interventions, but more high-quality studies are needed to support the routine use of any pictogram-based materials with liquid medications in the clinical settings.


Subject(s)
Health Communication/methods , Patient Education as Topic/methods , Pharmaceutical Preparations/administration & dosage , Audiovisual Aids , Caregivers , Comprehension , Health Literacy , Humans
10.
J Biol Regul Homeost Agents ; 29(1): 85-92, 2015.
Article in English | MEDLINE | ID: mdl-25864744

ABSTRACT

Signal transducers and activators of transcription (STAT) play critical roles in development, proliferation, and immune defense. However the consequences of STAT hyperactivity can predispose to diseases, including colorectal cancer. In the present study, we aimed to evaluate the function of STAT4 in human colorectal cancer (CRC). The expression of STAT4 was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was carried out to investigate the effects of lentivirus-mediated STAT4 shRNA (Lv-shSTAT4) on cell proliferation and invasive potential indicated by MTT and Transwell assays in CRC cell lines (SW480 and Caco2). As a consequence, it was found that the expression of STAT4 protein was significantly increased in CRC tissues compared with that in adjacent non-cancerous tissues (ANCT) (71.1% vs 44.4%, P=0.015), and was related with the Duke’s staging and depth of invasion in CRC patients (P=0.022; P=0.001). Silencing of STAT4 gene suppressed cell proliferation and invasion of CRC cells. Taken together, these findings demonstrate that increased expression of STAT4 is positively correlated with the depth of invasion in CRC patients, and inhibition of STAT4 expression represses the growth and invasion of CRC cells, suggesting that STAT4 may be a promising therapeutic target for the treatment of CRC.


Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Gene Silencing , STAT4 Transcription Factor/genetics , Caco-2 Cells/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Colorectal Neoplasms/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , RNA, Small Interfering , STAT4 Transcription Factor/metabolism
11.
ScientificWorldJournal ; 2014: 940502, 2014.
Article in English | MEDLINE | ID: mdl-25436237

ABSTRACT

Melamine formaldehyde (MF) resins have been synthesized at different reaction temperature and pH values. Different molar ratios of melamine and formaldehyde were used to synthesize the corresponding resins. The prepared resin samples were characterized by using molecular weight determination viscometry and thermogravimetric analysis (TGA). The maximum percentage of solid content (69.7%) was obtained at pH 8.5 and 75°C temperature. The molecular weight of MF resin was increased with an increase of melamine monomer concentration. The highest residual weight 14.125 wt.% was obtained with sample 10.


Subject(s)
Resins, Synthetic/chemical synthesis , Temperature , Triazines/chemical synthesis , Triazines/metabolism , Resins, Synthetic/metabolism
12.
AJNR Am J Neuroradiol ; 35(5): 920-7, 2014 May.
Article in English | MEDLINE | ID: mdl-24557705

ABSTRACT

BACKGROUND AND PURPOSE: IDH1 mutational status probably plays an important role in the predictive response for patients with astroglioma. This study explores whether DTI metrics are able to noninvasively detect IDH1 status in astrogliomas. MATERIALS AND METHODS: The DTI data of 112 patients with pathologically proven astroglioma (including 25, 12, and 10 cases with IDH1 mutation and 11, 11, and 43 cases without mutation in grades II, III, and IV, respectively) were retrospectively reviewed. The maximal fractional anisotropy, minimal ADC, ratio of maximal fractional anisotropy, and ratio of minimal ADC in the tumor body were measured. In the same World Health Organization grading, the imaging parameters of patients with and without IDH1 R132H mutation were compared by means of optimal metrics for detecting mutations. Receiver operating characteristic curve analysis was performed. RESULTS: The maximal fractional anisotropy and ratio of maximal fractional anisotropy values had statistical significance between patients with IDH1 R132H mutation and those without mutation in astrogliomas of grades II and III. The areas under the curve for maximal fractional anisotropy and ratio of maximal fractional anisotropy were both 0.92 in grade II and 0.80 and 0.82 in grade III. The minimal ADC value and ratio of minimal ADC value also demonstrated statistical significance between patients with mutation and those without mutation in all astroglioma grades. The areas under the curve for minimal ADC were 0.94 (II), 0.76 (III), and 0.66 (IV), and the areas under the curve for ratio of minimal ADC were 0.93 (II), 0.83 (III), and 0.70 (IV). CONCLUSIONS: Fractional anisotropy and ADC from DTI can noninvasively detect IDH1 R132H mutation in astrogliomas.


Subject(s)
Astrocytoma/genetics , Astrocytoma/pathology , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Diffusion Tensor Imaging/methods , Genetic Predisposition to Disease/genetics , Isocitrate Dehydrogenase/genetics , Adult , Female , Genetic Markers/genetics , Humans , Image Interpretation, Computer-Assisted/methods , Male , Middle Aged , Mutation/genetics , Polymorphism, Single Nucleotide/genetics , Prognosis , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity
13.
Clin Radiol ; 69(2): 179-85, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24188594

ABSTRACT

AIM: To present the neuroradiological and clinical characteristics of Ewing's sarcoma family of tumours (ESFTs) and to increase awareness of this neoplasm. MATERIALS AND METHODS: The magnetic resonance imaging (MRI) features and clinical presentations of seven patients with pathologically documented ESFTs were retrospectively analysed. The tumour location, morphological features, signal intensity, contrast enhancement characteristics, involvement of the paraspinal soft tissues, and adjacent bony structures were assessed. RESULTS: Most of the ESFTs in young adults were well-circumscribed. The present study demonstrated that ESFTs often have a hypo- or iso-intense signal on T1-weighted imaging and an iso-intense signal on T2-weighted imaging. Spinal ESFTs tended to present homogeneous signal intensity and diffuse enhancement. ESFTs are more likely to occur in the thoracic spine and later to infiltrate into the paraspinal area or vertebral bone. A broad dural attachment is another common feature in the cases presented here. CONCLUSIONS: ESFT is a rare neoplasm that can have significant overlap in imaging appearance compared with other spinal neoplasms. A well-demarcated extradural mass invading the paraspinal soft or vertebral bones, with iso-intense on T2 weighted imaging and homogeneous enhancement could facilitate the diagnosis of spinal ESFT.


Subject(s)
Magnetic Resonance Imaging/methods , Sarcoma, Ewing/diagnosis , Spinal Neoplasms/diagnosis , Adolescent , Adult , Child , Contrast Media , Female , Gadolinium DTPA , Humans , Image Enhancement/methods , Male , Middle Aged , Retrospective Studies , Spine/pathology , Young Adult
14.
Mol Ecol Resour ; 9(1): 360-4, 2009 Jan.
Article in English | MEDLINE | ID: mdl-21564650

ABSTRACT

We present 25 polymorphic microsatellite loci for Intsia palembanica, a highly valued timber species in the Indo-Malayan region, Australia and western Pacific islands. Microsatellite loci were tested for polymorphism across a total of 76 individuals from three natural populations from Irian Jaya, Indonesia. The average number of alleles for these microsatellites was 12.1 per locus, ranging from four to 19. The observed heterozygosity within the natural populations ranged from 0.01 to 0.96. The markers will enable us to evaluate the spatial-temporal population genetic structure and gene flow dynamics among populations. They can also be used for tracking and tracing wood from legally logged concessions.

15.
Ann Oncol ; 19(5): 915-9, 2008 May.
Article in English | MEDLINE | ID: mdl-18245778

ABSTRACT

BACKGROUND: Low tumour expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) have been linked with improved outcome for colorectal cancer (CRC) patients treated with 5-fluorouracil (5-FU). It is unclear whether this occurs because such tumours have better prognosis or they are more sensitive to 5-FU treatment. PATIENTS AND METHODS: Associations between TS, DPD and TP levels, determined by tissue microarrays and immunohistochemistry, and survival was evaluated in 945 CRC patients according to treatment status. RESULTS: Low TS and DPD expression associated with worse prognosis in stage II [hazard ratio (HR) = 1.69, 95% confidence interval (CI) (1.09-2.63) and HR = 1.92 (95% CI 1.23-2.94), respectively] and stage III CRC patients treated by surgery alone [HR = 1.39 (95% CI 0.92-2.13) and HR = 1.49 (95% CI 1.02-2.17), respectively]. Low TS, DPD and TP associated with trends for better outcome in stage III patients treated with 5-FU [HR = 0.81 (95% CI 0.49-1.33), HR = 0.70 (95% CI 0.42-1.15) and HR = 0.66 (95% CI 0.39-1.12), respectively]. CONCLUSION: Low TS and DPD expression are prognostic for worse outcome in CRC patients treated by surgery alone, whereas low TS, DPD and TP expression are prognostic for better outcome in patients treated with 5-FU chemotherapy. These results provide indirect evidence that low TS, DPD and TP protein expression are predictive of good response to 5-FU chemotherapy.


Subject(s)
Adenocarcinoma/enzymology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/enzymology , Fluorouracil/pharmacokinetics , Neoplasm Proteins/analysis , Thymidine Phosphorylase/analysis , Thymidylate Synthase/analysis , Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Chemotherapy, Adjuvant , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Dihydrouracil Dehydrogenase (NADP)/analysis , Drug Resistance, Neoplasm , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Neoplasm Staging , Prognosis , Survival Analysis
16.
J Chromatogr A ; 1072(2): 159-68, 2005 Apr 29.
Article in English | MEDLINE | ID: mdl-15887485

ABSTRACT

This study evaluates the potential of immobilized artificial membrane (IAM) chromatography, in combination with other physicochemical descriptors for high-throughput absorption profiling during lead optimization. An IAM chromatographic method was developed and validated. Absorption profiles of 32 structurally diverse compounds (acidic, basic, neutral and amphoteric) were then evaluated based on their IAM retention factor (log k'IAM), molecular weight (MW), calculated log P (C log P), polar surface area (PSA), hydrogen bonding capacity (HBD and HBA) and calculated Caco-2 permeability (QPCaco). Using regression and stepwise regression analysis, experimental Caco-2 permeability was correlated against log k'IAM and a combination of various physicochemical variables for quantitative structural-permeability relationship (QSPR) study. For the 32 structurally diverse compounds, log k'IAM correlated poorly with Caco-2 permeability values (R2 = 0.227). Stepwise regression analysis confirmed that Clog, PSA, HBD and HBA parameters are not statistically significant and can be eliminated. Correlation between Caco-2 cell uptake and log k'IAM was enhanced when molecular size factor (MW) was included (R2 = 0.555). The exclusion of 11 compounds (paracellularly and actively transported, Pgp substrates and blocker, and molecules with MW lesser than 200 and greater than 800) improved the correlation between Caco-2 permeability, IAM and MW factors to R2 value of 0.84. The results showed that IAM chromatography can only profile the passive absorption of drug molecules. Finally, it was confirmed in this study that the IAM model can accurately identify the Caco-2 permeability of nontransported Pgp substrates, such as verapamil and ketoconazole, through passive permeation because of their high permeability. IAM chromatography, combined with molecular size factor (MW), is useful for elucidating biopartitioning mechanism of drugs.


Subject(s)
Cell Membrane Permeability , Chromatography, High Pressure Liquid/methods , Membranes, Artificial , Caco-2 Cells , Humans , Hydrogen Bonding , Permeability , Spectrophotometry, Ultraviolet
20.
Plant Physiol ; 127(3): 998-1011, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11706181

ABSTRACT

In Arabidopsis, fertilization induces the epidermal cells of the outer ovule integument to differentiate into a specialized seed coat cell type producing extracellular pectinaceous mucilage and a volcano-shaped secondary cell wall. Differentiation involves a regulated series of cytological events including growth, cytoplasmic rearrangement, mucilage synthesis, and secondary cell wall production. We have tested the potential of Arabidopsis seed coat epidermal cells as a model system for the genetic analysis of these processes. A screen for mutants defective in seed mucilage identified five novel genes (MUCILAGE-MODIFIED [MUM]1-5). The seed coat development of these mutants, and that of three previously identified ones (TRANSPARENT TESTA GLABRA1, GLABRA2, and APETALA2) were characterized. Our results show that the genes identified define several events in seed coat differentiation. Although APETALA2 is needed for differentiation of both outer layers of the seed coat, TRANSPARENT TESTA GLABRA1, GLABRA2, and MUM4 are required for complete mucilage synthesis and cytoplasmic rearrangement. MUM3 and MUM5 may be involved in the regulation of mucilage composition, whereas MUM1 and MUM2 appear to play novel roles in post-synthesis cell wall modifications necessary for mucilage extrusion.


Subject(s)
Arabidopsis Proteins , Arabidopsis/genetics , Homeodomain Proteins/metabolism , Nuclear Proteins/metabolism , Pectins/biosynthesis , Plant Epidermis/growth & development , Plant Proteins/metabolism , beta-Galactosidase , Arabidopsis/cytology , Arabidopsis/growth & development , Arabidopsis/ultrastructure , Cell Differentiation , Cell Wall/genetics , Cell Wall/physiology , Cell Wall/ultrastructure , Fertilization , Homeodomain Proteins/genetics , Morphogenesis , Mutagenesis , Nuclear Proteins/genetics , Pectins/metabolism , Phenotype , Plant Epidermis/genetics , Plant Epidermis/ultrastructure , Plant Proteins/genetics , Ruthenium Red , Seeds/genetics , Seeds/growth & development , Seeds/ultrastructure , Zygote/growth & development
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