ABSTRACT
It is essential that communities at risk from TB are involved in TB research. Community advisory groups (CAGs) are one mechanism for involving communities in research and creating platforms for discussions between researchers and community members. We organised a CAG meeting with community members and people with lived experience in Ho Chi Minh City, Vietnam, to explore the community's knowledge about TB and their perspectives on different diagnostic tests in Vietnam, a low-middle-income country with a high TB burden. Researchers shared basic information and addressed questions about TB. CAG members commented on preference of TB screening tests, and suggested that chest X-rays and blood tests were more acceptable than sputum tests because of the difficulty in sputum expectoration. In addition, clinical studies that required fewer visits to the hospitals would be preferred, even if this meant a greater reliance on blood sampling.
Il est essentiel que les communautés exposées au risque de TB soient impliquées dans la recherche sur la TB. Les groupes consultatifs communautaires (CAG, pour l'anglais « community advisory groups ¼) constituent un mécanisme permettant d'impliquer les communautés dans la recherche et de créer des plateformes de discussion entre les chercheurs et les membres de la communauté. Nous avons organisé une réunion du CAG avec des membres de la communauté et des personnes ayant une expérience vécue à Ho Chi Minh Ville, au Viêt Nam, afin d'explorer les connaissances de la communauté sur la TB et leurs perspectives sur les différents tests de diagnostic au Viêt Nam, un pays à revenu faible et moyen où la charge de la TB est élevée. Les chercheurs ont partagé des informations de base et répondu à des questions sur la TB. Les membres du CAG ont fait part de leur préférence pour les tests de dépistage de la TB et ont suggéré que les radiographies pulmonaires et les analyses de sang étaient plus acceptables que les tests d'expectoration en raison de la difficulté d'expectoration des crachats. En outre, les études cliniques qui nécessitent moins de visites dans les hôpitaux seraient préférées, même si cela implique une plus grande dépendance à l'égard des prélèvements sanguins.
ABSTRACT
PM2.5 pollution is a serious problem in Vietnam and around the world, having bad impacts on human health, animals and environment. Regular monitoring at a large scale is important to assess the status of air pollution, develop solutions and evaluate the effectiveness of policy implementation. However, air quality monitoring stations in Vietnam are limited. In this article, we propose an approach to estimate daily PM2.5 concentration from 2012 to 2020 over the Vietnamese territory, which is strongly affected by cloudy conditions, using a modern statistical model named Mixed Effect Model (MEM) on a dataset consisting of ground PM2.5 measurements, integrated satellite Aerosol Optical Depth (AOD), meteorological and land use maps. The result of this approach is the first long-term, full coverage and high quality PM2.5 dataset of Vietnam. The daily mean PM2.5 maps have high validation results in comparison with ground PM2.5 measurement (Pearson r of 0.87, R2 of 0.75, RMSE of 11.76 µg/m3, and MRE of 36.57 % on a total of 13,886 data samples). The aggregated monthly and annual average maps from 2012 to 2020 in Vietnam have outstanding quality when compared with another global PM2.5 product. The PM2.5 concentration maps has shown spatial distribution and seasonal variations of PM2.5 concentration in Vietnam in a long period from 2012 to 2020 and has been used in other studies and applications in the environment and public health at the national scale, which has not been possible before because of the lack of monitoring stations and an appropriate PM2.5 modeling approach.
Subject(s)
Air Pollutants , Air Pollution , Humans , Particulate Matter/analysis , Air Pollutants/analysis , Environmental Monitoring/methods , Vietnam , Air Pollution/analysis , Aerosols/analysisABSTRACT
PURPOSE: Circulating microRNAs (miRNAs) are potential diagnostic biomarkers for breast cancer (BC). The application of miRNA panels could improve the performance of screening tests. Here, we integrated bioinformatic tools and meta-analyses to select circulating miRNAs with high diagnostic accuracy and combined these markers to develop diagnostic panels for BC. METHODS: Analyses across databases were performed to identify potential BC-related circulating miRNAs. Next, a comprehensive meta-analysis was conducted for each miRNA following the PRISMA guidelines. An electronic and manual search for relevant literature was carried out by two reviewers through PubMed, ScienceDirect, Biomed Central, and Google Scholar. The quality of the included studies was assessed using the QUADAS-2, and the statistical analyses were performed using R software 4.1.1. Finally, the accurate biomarkers confirmed through meta-analyses were combined into diagnostic models for BC. RESULTS: Twenty-seven circulating miRNAs were identified as BC-related by bioinformatic tools. After screening, only 10 miRNAs presented in 45 studies were eligible for meta-analyses. By assessing pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, 8 miRNAs (miR-21, miR-30b, miR-125b, miR-145, miR221 miR-222, and miR-335) were revealed as promising BC diagnostic biomarkers. Two panels constructed from these miRNAs showed excellent diagnostic accuracy for BC, with areas under the SROC curve of 0.917 and 0.944. CONCLUSION: We identified 8 potential circulating miRNAs and 2 diagnostic models that are useful for diagnosing BC. However, the established miRNA panels have not been tested in any experimental studies and thus should be validated in large case-control studies for clinical use.
Subject(s)
Breast Neoplasms , Circulating MicroRNA , MicroRNAs , Biomarkers , Biomarkers, Tumor/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Female , Humans , MicroRNAs/genetics , Odds RatioABSTRACT
Dengue viruses (DENV serotypes 1-4) and Zika virus (ZIKV) are related flaviviruses that continue to be a public health concern, infecting hundreds of millions of people annually. The traditional live-attenuated virus vaccine approach has been challenging for the four DENV serotypes because of the need to achieve balanced replication of four independent vaccine components. Subunit vaccines represent an alternative approach that may circumvent problems inherent with live-attenuated DENV vaccines. In mature virus particles, the envelope (E) protein forms a homodimer that covers the surface of the virus and is the major target of neutralizing antibodies. Many neutralizing antibodies bind to quaternary epitopes that span across both E proteins in the homodimer. For soluble E (sE) protein to be a viable subunit vaccine, the antigens should be easy to produce and retain quaternary epitopes recognized by neutralizing antibodies. However, WT sE proteins are primarily monomeric at conditions relevant for vaccination and exhibit low expression yields. Previously, we identified amino acid mutations that stabilize the sE homodimer from DENV2 and dramatically raise expression yields. Here, we tested whether these same mutations raise the stability of sE from other DENV serotypes and ZIKV. We show that the mutations raise thermostability for sE from all the viruses, increase production yields from 4-fold to 250-fold, stabilize the homodimer, and promote binding to dimer-specific neutralizing antibodies. Our findings suggest that these sE variants could be valuable resources in the efforts to develop effective subunit vaccines for DENV serotypes 1 to 4 and ZIKV.
Subject(s)
Dengue Virus , Vaccines, Subunit , Viral Envelope Proteins , Viral Vaccines , Zika Virus , Antibodies, Neutralizing , Antibodies, Viral , Cross Reactions , Dengue/prevention & control , Dengue Virus/genetics , Epitopes , Humans , Mutation , Vaccines, Attenuated , Vaccines, Subunit/genetics , Viral Envelope Proteins/genetics , Viral Vaccines/genetics , Zika Virus/genetics , Zika Virus Infection/prevention & controlABSTRACT
Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) is a method of choice for quantifying micro RNAs (miRNAs). Typically, RT-qPCR data are normalized to reference genes. While miRNAs are used for diagnosing and subtyping breast cancer, various studies show their deregulation in this condition, thus, undermining miRNAs' utility as a reference. This review examines the expression pattern of miR-16 and suggests normalization approaches for breast cancer. We analyzed the data from selected peer-reviewed studies to calculate the standardized mean difference (SMD) with subsequent Chi-square testing and identified the difference in miR-16 expression between breast cancer patients and healthy controls. With a negative SMD value of-0.56 and Chi-square of 62.62 (p-value = 0.05), the deregulation of miR-16 in breast cancer was confirmed. High variance in the stability value (SV) of miR-16 expression levels confirmed its inappropriateness as a control gene in breast cancer. The combination of miR-16 and miR-425 was confirmed as an accurate endogenous control.
Subject(s)
Breast Neoplasms , MicroRNAs , Breast Neoplasms/genetics , Female , Gene Expression Profiling , Humans , MicroRNAs/genetics , Real-Time Polymerase Chain ReactionABSTRACT
Dengue virus (DENV) is a worldwide health burden, and a safe vaccine is needed. Neutralizing antibodies bind to quaternary epitopes on DENV envelope (E) protein homodimers. However, recombinantly expressed soluble E proteins are monomers under vaccination conditions and do not present these quaternary epitopes, partly explaining their limited success as vaccine antigens. Using molecular modeling, we found DENV2 E protein mutations that induce dimerization at low concentrations (<100 pM) and enhance production yield by more than 50-fold. Cross-dimer epitope antibodies bind to the stabilized dimers, and a crystal structure resembles the wild-type (WT) E protein bound to a dimer epitope antibody. Mice immunized with the stabilized dimers developed antibodies that bind to E dimers and not monomers and elicited higher levels of DENV2-neutralizing antibodies compared to mice immunized with WT E antigen. Our findings demonstrate the feasibility of using structure-based design to produce subunit vaccines for dengue and other flaviviruses.
ABSTRACT
INTRODUCTION: Breast cancer (BC), a heterogeneous disease, features microRNA-related single nucleotide polymorphisms (miRSNPs) as underlying factors of BC development, thus providing targets for novel diagnostic and therapeutic strategies. This study investigated miRSNPs in BC susceptibility in Australian Caucasian women. PATIENTS AND METHODS: The study population included patients 33 to 80 years of age stratified by molecular subtypes of breast tumors (luminal A, 47.59%), stage (stage I, 36.96%), tumor-type (ductal, 44.95%), grading (intermediate, 35.52%), size (10.1-25 mm, 31.14%), and lymph node (sentinel negative, 38.93%). Sixty-five miRSNPs underwent allelic analysis in two independent case-control cohorts (GU-CCQ-BB, 377 cases and 521 controls; GRC-BC, 267 cases and 201 controls) using a MassARRAY platform. GU-CCQ-BB, GRC-BC, and the combined populations (BC-CA) (644 cases and 722 controls) underwent independent statistical analysis. RESULTS: In the GU-CCQ-BB population, miRSNPs TET2-rs7670522, ESR1-rs2046210, FGFR2-rs1219648, MIR210-rs1062099, HIF1A-rs2057482, and CASC16-rs4784227 were found to be associated with increased BC risk (P ≤ .05). Only ESR1-rs2046210 was also significantly associated (P ≤ .05) when replicated in the GRC-BC and BC-CA populations. No significant association was correlated with BC-clinical features (pathological types and ER/PR/HER2 status); however, MIR210-rs1062099 was found to be significantly associated (P ≤ .05) with age (>50 years) in the GU-CCQ-BB cohort. CONCLUSION: This is the first study to demonstrate the association of MIR210-rs1062099 and TET2-rs7670522 with increased BC risk. Additionally, four previously reported SNPs (ESR1-rs2046210, FGFR2-rs1219648, HIF1A-rs2057482, and CASC16-rs4784227) were confirmed as BC risk variants. Replication and functional studies in larger Caucasian cohorts are necessary to elucidate the role of these miRSNPS in the development of BC.
Subject(s)
Breast Neoplasms/metabolism , MicroRNAs/metabolism , White People/statistics & numerical data , Adult , Aged , Aged, 80 and over , Australia , Breast Neoplasms/pathology , Case-Control Studies , Female , Genetic Predisposition to Disease , Humans , Middle Aged , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
Satellite observations for regional air quality assessment rely on comprehensive spatial coverage, and daily monitoring with reliable, cloud-free data quality. We investigated spatiotemporal variation and data quality of two global satellite Aerosol Optical Depth (AOD) products derived from MODIS and VIIRS imagery. AOD is considered an essential atmospheric parameter strongly related to ground Particulate Matter (PM) in Southeast Asia (SEA). We analyze seasonal variation, urban/rural area influence, and biomass burning effects on atmospheric pollution. Validation indicated a strong relationship between AERONET ground AOD and both MODIS AOD (R2â¯=â¯0.81) and VIIRS AOD (R2â¯=â¯0.68). The monthly variation of satellite AOD and AERONET AOD reflects two seasonal trends of air quality separately for mainland countries including Myanmar, Laos, Cambodia, Thailand, Vietnam, and Taiwan, Hong Kong, and for maritime countries consisting of Indonesia, Philippines, Malaysia, Brunei, Singapore, and Timor Leste. The mainland SEA has a pattern of monthly AOD variation in which AODs peak in March/April, decreasing during wet season from May-September, and increasing to the second peak in October. However, in maritime SEA, AOD concentration peaks in October. The three countries with the highest annual satellite AODs are Singapore, Hong Kong, and Vietnam. High urban population proportions in Singapore (40.7%) and Hong Kong (21.6%) were associated with high AOD concentrations as expected. AOD values in SEA urban areas were a factor of 1.4 higher than in rural areas, with respective averages of 0.477 and 0.336. The AOD values varied proportionately to the frequency of biomass burning in which both active fires and AOD peak in March/April and September/October. Peak AOD in September/October in some countries could be related to pollutant transport of Indonesia forest fires. This study analyzed satellite aerosol product quality in relation to AERONET in SEA countries and highlighted framework of air quality assessment over a large, complicated region.
Subject(s)
Aerosols/analysis , Air Pollutants/analysis , Environmental Monitoring/methods , Particulate Matter/analysis , Spatio-Temporal Analysis , Air Pollution/analysis , Asia, Southeastern , Biomass , Fires , Seasons , Spacecraft , Urbanization , WildfiresABSTRACT
Cytochrome P450 (P450) enzymes are major catalysts involved in the oxidations of most drugs, steroids, carcinogens, fat-soluble vitamins, and natural products. The binding of substrates to some of the 57 human P450s and other mammalian P450s is more complex than a two-state system and has been proposed to involve mechanisms such as multiple ligand occupancy, induced-fit, and conformational-selection. Here, we used kinetic analysis of binding with multiple concentrations of substrates and computational modeling of these data to discern possible binding modes of several human P450s. We observed that P450 2D6 binds its ligand rolapitant in a mechanism involving conformational-selection. P450 4A11 bound the substrate lauric acid via conformational-selection, as did P450 2C8 with palmitic acid. Binding of the steroid progesterone to P450 21A2 was also best described by a conformational-selection model. Hexyl isonicotinate binding to P450 2E1 could be described by either a conformational-selection or an induced-fit model. Simulation of the binding of the ligands midazolam, bromocriptine, testosterone, and ketoconazole to P450 3A4 was consistent with an induced-fit or a conformational-selection model, but the concentration dependence of binding rates for varying both P450 3A4 and midazolam concentrations revealed discordance in the parameters, indicative of conformational-selection. Binding of the P450s 2C8, 2D6, 3A4, 4A11, and 21A2 was best described by conformational-selection, and P450 2E1 appeared to fit either mode. These findings highlight the complexity of human P450-substrate interactions and that conformational-selection is a dominant feature of many of these interactions.
Subject(s)
Cytochrome P-450 CYP3A/metabolism , Cytochrome P-450 Enzyme System/metabolism , Protein Conformation/drug effects , Catalysis , Cytochrome P-450 CYP2D6/metabolism , Cytochrome P-450 CYP2E1/metabolism , Cytochrome P-450 Enzyme Inhibitors/metabolism , Cytochrome P-450 Enzyme System/physiology , Humans , Kinetics , Lauric Acids , Ligands , Molecular Conformation , Oxidation-Reduction , Palmitic Acid , Protein Binding/physiology , Spiro Compounds , Substrate Specificity/physiologyABSTRACT
The lumen of the endoplasmic reticulum (ER) provides an oxidizing environment to aid in the formation of disulfide bonds, which is tightly regulated by both antioxidant proteins and small molecules. On the cytoplasmic side of the ER, cytochrome P450 (P450) proteins have been identified as a superfamily of enzymes that are important in the formation of endogenous chemicals as well as in the detoxication of xenobiotics. Our previous report described oxidative inhibition of P450 Family 4 enzymes via oxidation of the heme-thiolate cysteine to a sulfenic acid (-SOH) (Albertolle, M. E. et al. (2017) J. Biol. Chem. 292, 11230-11242). Further proteomic analyses of murine kidney and liver microsomes led to the finding that a number of other drug-metabolizing enzymes located in the ER are also redox-regulated in this manner. We expanded our analysis of sulfenylated enzymes to human liver and kidney microsomes. Evaluation of the sulfenylation, catalytic activity, and spectral properties of P450s 1A2, 2C8, 2D6, and 3A4 led to the identification of two classes of redox sensitivity in P450 enzymes: heme-thiolate-sensitive and thiol-insensitive. These findings provide evidence for a mammalian P450 regulatory mechanism, which may also be relevant to other drug-metabolizing enzymes. (Data are available via ProteomeXchange with identifier PXD007913.).
Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Kidney/enzymology , Microsomes, Liver/enzymology , Pharmaceutical Preparations/metabolism , Sulfenic Acids/metabolism , Animals , Biocatalysis , Cysteine/metabolism , Humans , Hydrogen Peroxide/toxicity , Mice, Transgenic , Oxidation-Reduction , Recombinant Proteins/metabolism , Staining and Labeling , Sulfhydryl Compounds/metabolismABSTRACT
Cytochrome P450 (P450) 17A1 catalyzes the oxidations of progesterone and pregnenolone and is the major source of androgens. The enzyme catalyzes both 17α-hydroxylation and a subsequent 17α,20-lyase reaction, and several mechanisms have been proposed for the latter step. Zebrafish P450 17A2 catalyzes only the 17α-hydroxylations. We previously reported high similarity of the crystal structures of zebrafish P450 17A1 and 17A2 and human P450 17A1. Five residues near the heme, which differed, were changed. We also crystallized this five-residue zebrafish P450 17A1 mutant, and the active site still resembled the structure in the other proteins, with some important differences. These P450 17A1 and 17A2 mutants had catalytic profiles more similar to each other than did the wildtype proteins. Docking with these structures can explain several minor products, which require multiple enzyme conformations. The 17α-hydroperoxy (OOH) derivatives of the steroids were used as oxygen surrogates. Human P450 17A1 and zebrafish P450s 17A1 and P450 17A2 readily converted these to the lyase products in the absence of other proteins or cofactors (with catalytically competent kinetics) plus hydroxylated 17α-hydroxysteroids. The 17α-OOH results indicate that a "Compound I" (FeO3+) intermediate is capable of formation and can be used to rationalize the products. We conclude that zebrafish P450 17A2 is capable of lyase activity with the 17α-OOH steroids because it can achieve an appropriate conformation for lyase catalysis in this system that is precluded in the conventional reaction.
Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Steroid 17-alpha-Hydroxylase/metabolism , Animals , Humans , Hydroxysteroids/metabolism , Protein Conformation , ZebrafishABSTRACT
Recently, zebrafish and human cytochrome P450 (P450) 27C1 enzymes have been shown to be retinoid 3,4-desaturases. The enzyme is unusual among mammalian P450s in that the predominant oxidation is a desaturation and in that hydroxylation represents only a minor pathway. We show by proteomic analysis that P450 27C1 is localized to human skin, with two proteins of different sizes present, one being a cleavage product of the full-length form. P450 27C1 oxidized all-trans-retinol to 3,4-dehydroretinol, 4-hydroxy (OH) retinol, and 3-OH retinol in a 100:3:2 ratio. Neither 3-OH nor 4-OH retinol was an intermediate in desaturation. No kinetic burst was observed in the steady state; neither the rate of substrate binding nor product release was rate-limiting. Ferric P450 27C1 reduction by adrenodoxin was 3-fold faster in the presence of the substrate and was â¼5-fold faster than the overall turnover. Kinetic isotope effects of 1.5-2.3 (on kcat/Km ) were observed with 3,3-, 4,4-, and 3,3,4,4-deuterated retinol. Deuteration at C-4 produced a 4-fold increase in 3-hydroxylation due to metabolic switching, with no observable effect on 4-hydroxylation. Deuteration at C-3 produced a strong kinetic isotope effect for 3-hydroxylation but not 4-hydroxylation. Analysis of the products of deuterated retinol showed a lack of scrambling of a putative allylic radical at C-3 and C-4. We conclude that the most likely catalytic mechanism begins with abstraction of a hydrogen atom from C-4 (or possibly C-3) initiating the desaturation pathway, followed by a sequential abstraction of a hydrogen atom or proton-coupled electron transfer. Adrenodoxin reduction and hydrogen abstraction both contribute to rate limitation.
Subject(s)
Cytochrome P450 Family 27/metabolism , Gene Expression Regulation, Enzymologic , Mitochondria/enzymology , Skin/enzymology , Vitamin A/analogs & derivatives , Vitamin A/metabolism , Biocatalysis , Cytochrome P450 Family 27/genetics , Diterpenes , Gene Expression Profiling , Humans , Hydrogenation , Hydroxylation , Isoenzymes/genetics , Isoenzymes/metabolism , Kinetics , Molecular Structure , Organ Specificity , Oxidation-Reduction , Peptide Fragments/genetics , Peptide Fragments/metabolism , Proteolysis , Proteomics/methods , Stereoisomerism , Substrate Specificity , Vitamin A/chemistryABSTRACT
Cytochrome P450 46A1 (CYP46A1, cholesterol 24-hydroxylase) is the enzyme responsible for the majority of cholesterol elimination from the brain. Previously, we found that the anti-HIV drug efavirenz (EFV) can pharmacologically activate CYP46A1 in mice. Herein, we investigated whether CYP46A1 could also be activated by endogenous compounds, including major neurotransmitters. In vitro experiments with purified recombinant CYP46A1 indicated that CYP46A1 is activated by l-glutamate (l-Glu), l-aspartate, γ-aminobutyric acid, and acetylcholine, with l-Glu eliciting the highest increase (3-fold) in CYP46A1-mediated cholesterol 24-hydroxylation. We also found that l-Glu and other activating neurotransmitters bind to the same site on the CYP46A1 surface, which differs from the EFV-binding site. The other principal differences between EFV and l-Glu in CYP46A1 activation include an apparent lack of l-Glu binding to the P450 active site and different pathways of signal transduction from the allosteric site to the active site. EFV and l-Glu similarly increased the CYP46A1 kcat, the rate of the "fast" phase of the enzyme reduction by the redox partner NADPH-cytochrome P450 oxidoreductase, and the amount of P450 reduced. Spectral titrations with cholesterol, in the presence of EFV or l-Glu, suggest that water displacement from the heme iron can be affected in activator-bound CYP46A1. Moreover, EFV and l-Glu synergistically activated CYP46A1. Collectively, our in vitro data, along with those from previous cell culture and in vivo studies by others, suggest that l-Glu-induced CYP46A1 activation is of physiological relevance.
Subject(s)
Acetylcholine/metabolism , Aspartic Acid/metabolism , Cholesterol 24-Hydroxylase/metabolism , Glutamic Acid/metabolism , Models, Molecular , Nerve Tissue Proteins/agonists , gamma-Aminobutyric Acid/metabolism , Acetylcholine/chemistry , Alkynes , Allosteric Regulation/drug effects , Amino Acid Substitution , Anti-HIV Agents/chemistry , Anti-HIV Agents/metabolism , Anti-HIV Agents/pharmacology , Aspartic Acid/chemistry , Benzoxazines/chemistry , Benzoxazines/metabolism , Benzoxazines/pharmacology , Binding Sites , Biocatalysis/drug effects , Cholesterol 24-Hydroxylase/chemistry , Cholesterol 24-Hydroxylase/genetics , Cyclopropanes , Deuterium Exchange Measurement , Enzyme Activation/drug effects , Glutamic Acid/chemistry , Ligands , Molecular Docking Simulation , Mutagenesis, Site-Directed , Mutation , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Peptide Fragments/chemistry , Peptide Fragments/genetics , Peptide Fragments/metabolism , Protein Conformation , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/metabolism , gamma-Aminobutyric Acid/chemistryABSTRACT
In this study, we estimate rice residue, associated burning emissions, and compare results with existing emissions inventories employing a bottom-up approach. We first estimated field-level post-harvest rice residues, including separate fuel-loading factors for rice straw and rice stubble. Results suggested fuel-loading factors of 0.27 kg m-2 (±0.033), 0.61 kg m-2 (±0.076), and 0.88 kg m-2 (±0.083) for rice straw, stubble, and total post-harvest biomass, respectively. Using these factors, we quantified potential emissions from rice residue burning and compared our estimates with other studies. Our results suggest total rice residue burning emissions as 2.24 Gg PM2.5, 36.54 Gg CO and 567.79 Gg CO2 for Hanoi Province, which are significantly higher than earlier studies. We attribute our higher emission estimates to improved fuel-loading factors; moreover, we infer that some earlier studies relying on residue-to-product ratios could be underestimating rice residue emissions by more than a factor of 2.3 for Hanoi, Vietnam. Using the rice planted area data from the Vietnamese government, and combining our fuel-loading factors, we also estimated rice residue PM2.5 emissions for the entirety of Vietnam and compared these estimates with an existing all-sources emissions inventory, and the Global Fire Emissions Database (GFED). Results suggest 75.98 Gg of PM2.5 released from rice residue burning accounting for 12.8% of total emissions for Vietnam. The GFED database suggests 42.56 Gg PM2.5 from biomass burning with 5.62 Gg attributed to agricultural waste burning indicating satellite-based methods may be significantly underestimating emissions. Our results not only provide improved residue and emission estimates, but also highlight the need for emissions mitigation from rice residue burning.
ABSTRACT
In humans, a considerable fraction of the retinoid pool in skin is derived from vitamin A2 (all-trans 3,4-dehydroretinal). Vitamin A2 may be locally generated by keratinocytes, which can convert vitamin A1 (all-trans retinol) into vitamin A2 in cell culture. We report that human cytochrome P450 (hP450) 27C1, a previously 'orphan' enzyme, can catalyze this reaction. Purified recombinant hP450 27C1 bound and desaturated all-trans retinol, retinal, and retinoic acid, as well as 11-cis-retinal. Although the physiological role of 3,4-dehydroretinoids in humans is unclear, we have identified hP450 27C1 as an enzyme capable of efficiently mediating their formation.
Subject(s)
Cytochrome P450 Family 27/metabolism , Retinoids/metabolism , HumansABSTRACT
OBJECTIVE: To follow malaria prospectively in an ethnic minority commune in the south of Viet Nam with high malaria transmission and seasonal fluctuation, during malaria control interventions using insecticide-treated bednets (ITBNs) and early diagnosis and treatment (EDT) of symptomatic patients. METHODS: From 1994 onwards the following interventions were used: distribution of ITBNs to all households with biannual reimpregnation; construction of a health post and appointment of staff trained in microscopic diagnosis and treatment of malaria; regular supply of materials and drugs; annual cross-sectional malaria surveys with treatment of all parasitaemic subjects, and a programme of community involvement and health education. Surveys were held yearly at the end of the rainy season. During the surveys, demographic data were updated. Diagnosis and treatment of malaria were free of charge. Plasmodium falciparum infection was treated with artesunate and P. vivax infection with chloroquine plus primaquine. FINDINGS: The baseline survey in 1994 recorded 716 inhabitants. Of the children under 2 years of age, 37% were parasitaemic; 56% of children aged 2-10 years, and 35% of the remaining population were parasitaemic. P. falciparum accounted for 73-79% of these infections. The respective splenomegaly rates for the above-mentioned age groups were 20%, 56%, and 32%. In 1999, the proportion of parasitaemic subjects was 4%, 7% and 1%, respectively, of which P.falciparum contributed 56%. The splenomegaly rate was 0%, 5% and 2%, respectively. CONCLUSIONS: A combination of ITBNs and EDT, provided free of charge, complemented by annual diagnosis and treatment during malaria surveys and community involvement with health education successfully brought malaria under control. This approach could be applied to other regions in the south of Viet Nam and provides a sound basis for further studies in other areas with different epidemiological patterns of malaria.
Subject(s)
Communicable Disease Control/organization & administration , Malaria, Falciparum/prevention & control , Malaria, Vivax/prevention & control , Antimalarials/therapeutic use , Bedding and Linens/statistics & numerical data , Child , Child, Preschool , Female , Health Education , Health Knowledge, Attitudes, Practice , Humans , Insecticides , Longitudinal Studies , Malaria, Falciparum/diagnosis , Malaria, Falciparum/drug therapy , Malaria, Falciparum/ethnology , Malaria, Vivax/diagnosis , Malaria, Vivax/drug therapy , Malaria, Vivax/ethnology , Male , Primaquine/therapeutic use , Pyrethrins , Vietnam/epidemiologyABSTRACT
Comparative analyses of lipids from fossil plants and from their extant counterparts were undertaken in order to test the taxonomic significance of lipids in palaeobotany. The comparison between lipids from a fossil Ginkgoaceae, Eretmophyllum andegavense, and its extant counterpart, Ginkgo biloba, revealed the presence of original molecules, dimethoxyalkylcoumarins, in lipids from both plants. Such compounds confirm, on chemical grounds the relationship between these extant and fossil Ginkgoaceaes. Moreover, differences in n-alkane distribution between E. andegavense and E. obtusum which are very similar morphologically, confirm that these fossil plants do not belong to the same species. Furthermore, comparative analyses of a fossil Cheirolepidiaceae, Frenelopsis alata, and its extant counterpart, the Cupressaceae Tetraclinis articulata, revealed some similarities between these two species although they do not belong to the same family. Otherwise, comparative analyses of fungi-infected and uninfected samples of F. alata demonstrated that these micro-organisms can significantly affect the chemical composition of fossil plant lipids. In conclusion, even if chemical analyses alone are not sufficient to determine the genus or species of a given fossil plant, they can precise the taxonomy of some specimens that have been previously studied by palaeobotanists.