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1.
Biomimetics (Basel) ; 8(6)2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37887617

RESUMO

The immune plasma algorithm (IP algorithm or IPA) is one of the most recent meta-heuristic techniques and models the fundamental steps of immune or convalescent plasma treatment, attracting researchers' attention once more with the COVID-19 pandemic. The IP algorithm determines the number of donors and the number of receivers when two specific control parameters are initialized and protects their values until the end of termination. However, determining which values are appropriate for the control parameters by adjusting the number of donors and receivers and guessing how they interact with each other are difficult tasks. In this study, we attempted to determine the number of plasma donors and receivers with an improved mechanism that depended on dividing the whole population into two sub-populations using a statistical measure known as the percentile and then a novel variant of the IPA called the percentile IPA (pIPA) was introduced. To investigate the performance of the pIPA, 22 numerical benchmark problems were solved by assigning different values to the control parameters of the algorithm. Moreover, two complex engineering problems, one of which required the filtering of noise from the recorded signal and the other the path planning of an unmanned aerial vehicle, were solved by the pIPA. Experimental studies showed that the percentile-based donor-receiver selection mechanism significantly contributed to the solving capabilities of the pIPA and helped it outperform well-known and state-of-art meta-heuristic algorithms.

2.
BMC Psychol ; 11(1): 206, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438811

RESUMO

Active citizenship is closely related to basic human values and patriotism, but empirical studies have lacked investigating these variables holistically. Likewise, the mediating role of patriotism between basic human values and active citizenship seems neglected. In this context, the current study examined the relationships between basic human values, patriotism, and active citizenship by grounding upon basic human values, individualism, and collectivism theories. Results revealed that constructive patriotism positively predicted all dimensions of active citizenship (political literacy, participation and protest, and social responsibility) and mediated the relationships between basic human values and active citizenship. Additionally, while stimulation and self-direction individual values, including motivational goals such as challenges in life, independent thought, and autonomy, were associated with the individual aspect of active citizenship (protest and individual responsibility), the values based on equality (benevolence) were related with the collectivist aspect of active citizenship (participation and social responsibility). One of the most influential findings was that the universalism value could only associate positively with active citizenship through constructive patriotism. Another impressive culture-specific result was that the political literacy dimension of active citizenship was positively related to power, which includes the goal of achieving individual success and dominating others. It can be evaluated as Turkish culture is more of a vertical collectivist because, historically and sociologically, a way of gaining power and status has been possible with politics and its cognitive equivalent, political literacy. The study also revealed that active citizenship is promoted through individual values based upon an individual's independent choices and collectivist values that support societal interests based on equality. In summary, the research mainly revealed that active citizenship is sustained by both individualist values (stimulation, self-direction) and collectivist values (universalism, benevolence), and constructive patriotism has a critical mediating role. Implications of the results were discussed with the relevant literature.


Assuntos
Cidadania , Motivação , Humanos , Adulto , Pesquisa Empírica , Responsabilidade Social
3.
Biotechnol Biofuels Bioprod ; 16(1): 90, 2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37245032

RESUMO

BACKGROUND: Rice (Oryza sativa) straw is a common waste product that represents a considerable amount of bound energy. This energy can be used for biogas production, but the rate and level of methane produced from rice straw is still low. To investigate the potential for an increased biogas production from rice straw, we have here utilized WRINKLED1 (WRI1), a plant AP2/ERF transcription factor, to increase triacylglycerol (TAG) biosynthesis in rice plants. Two forms of Arabidopsis thaliana WRI1 were evaluated by transient expression and stable transformation of rice plants, and transgenic plants were analyzed both for TAG levels and biogas production from straw. RESULTS: Both full-length AtWRI1, and a truncated form lacking the initial 141 amino acids (including the N-terminal AP2 domain), increased fatty acid and TAG levels in vegetative and reproductive tissues of Indica rice. The stimulatory effect of the truncated AtWRI1 was significantly lower than that of the full-length protein, suggesting a role for the deleted AP2 domain in WRI1 activity. Full-length AtWRI1 increased TAG levels also in Japonica rice, indicating a conserved effect of WRI1 in rice lipid biosynthesis. The bio-methane production from rice straw was 20% higher in transformants than in the wild type. Moreover, a higher producing rate and final yield of methane was obtained for rice straw compared with rice husks, suggesting positive links between methane production and a high amount of fatty acids. CONCLUSIONS: Our results suggest that heterologous WRI1 expression in transgenic plants can be used to improve the metabolic potential for bioenergy purposes, in particular methane production.

4.
Ann Plast Surg ; 90(1): 87-95, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36534107

RESUMO

ABSTRACT: After the first face transplantation from woman to woman we performed in our clinic, it was aimed to eliminate the lack of knowledge about the subject in the literature by transferring our experiences and long-term results to the problems we had with the patient. A 20-year-old patient underwent partial osteomyocutaneous facial transplant (22nd facial transplant), which included 2 functional units of the face. The patient had no major problems in the early period and had a good aesthetic appearance. In the postoperative period, the patient ended her social isolation and adopted the transplanted face.In the late period, secondary surgical interventions, management of the problems caused by immunosuppression, and the patient's living in a remote location to our clinic were the difficulties encountered. Six revision surgeries were performed after the transplantation. Due to immunosuppression, opportunistic infections and metabolic problems required intermittent hospitalization. The patient died at the end of 56 months because of complications secondary to immunosuppression.A successful transplant involves the management of long-term problems rather than a successful tissue transfer in the early period. In today's conditions, long-term success can be achieved with a good patient compliance, as well as each team member should take an active role in the team at the transplantation centers. More case series are needed to adapt the standard treatment and follow-up protocols for solid organ transplantations for composite tissue allotransplantations. This will be possible by sharing the results and experiences transparently in the centers where face transplantation is performed worldwide.


Assuntos
Transplante de Face , Alotransplante de Tecidos Compostos Vascularizados , Humanos , Feminino , Adulto Jovem , Adulto , Turquia , Terapia de Imunossupressão
6.
Vaccines (Basel) ; 10(12)2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36560437

RESUMO

Background: This study aimed to explore the effect of knowledge, COVID-19-related perceptions, and public trust on protective behaviors in Turkish people. Methods: Data were collected from an online survey (Turkish COVID-19 Snapshot Monitoring) conducted between July 2020 and January 2021. The recommended protective behaviors (hand cleaning, wearing a face mask, and physical distancing) to prevent COVID-19 were examined. The impacts of the following variables on protective behaviors were investigated using logistic regression analysis: knowledge, cognitive and affective risk perception, pandemic-related worry content, public trust, conspiracy thinking, and COVID-19 vaccine willingness. Results: Out of a total of 4210 adult respondents, 13.8% reported nonadherence to protection behavior, and 86.2% reported full adherence. Males and young (aged 18−30 years) people tend to show less adherence. Perceived self-efficacy, susceptibility, and correct knowledge were positively related to more adherence to protective behavior. Perceptual and emotional factors explaining protective behavior were perceived proximity, stress level, and worrying about the relatives who depended on them. Trust in health professionals and vaccine willingness were positive predictors, while conspiracy thinking and acquiring less information (<2, daily) were negative predictors. Unexpectedly, trust in the Ministry of Health showed a weak but negative association with protection behavior. Conclusions: Perceived stress, altruistic worries, and public trust seem to shape protection behaviors in addition to individuals' knowledge and cognitive risk perception in respondents. Males and young people may have a greater risk for nonadherence. Reliable, transparent, and culture-specific health communication that considers these issues is required.

7.
J Neural Transm (Vienna) ; 129(12): 1513-1526, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36334154

RESUMO

The kynurenine pathway (KP) and inflammation are substantial in depression pathogenesis. Although there is a crosstalk between the KP, inflammation, and neurotrophic factors, few studies examine these topics together. Novel medications may be developed by clarifying dysregulations related to inflammation, KP, and neurotrophic factors in treatment-resistant depression (TRD). We aimed to evaluate the serum levels of KP metabolites, proinflammatory biomarkers, and brain-derived neurotrophic factor (BDNF) in healthy controls (HC) and the patients with TRD whose followed up with three different treatments. Moreover, the effect of electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) on biomarkers was investigated. Study groups comprised a total of 30 unipolar TRD patients consisting of three separate patient groups (ECT = 8, rTMS = 10, pharmacotherapy = 12), and 9 HC. The decision to administer only pharmacotherapy or ECT/rTMS besides pharmacotherapy was given independently of this research by psychiatrists. Blood samples and symptom scores were obtained three times for patients. At baseline, quinolinic acid (QUIN) was higher in the patients with TRD compared to HC, whereas picolinic acid (PIC), PIC/QUIN, and PIC/3-hydroxykynurenine were lower. Baseline interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were higher in nonresponders and non-remitters. ECT had an acute effect on cytokines. In the rTMS group, tumor necrosis factor-α (TNF-α) decreased in time. PIC, QUIN, and aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) enzyme may play a role in TRD pathogenesis, and have diagnostic potential. rTMS and ECT have modulatory effects on low-grade inflammation seen in TRD. Baseline inflammation severity is predictive in terms of response and remission in depression.


Assuntos
Transtorno Depressivo Resistente a Tratamento , Eletroconvulsoterapia , Humanos , Cinurenina , Projetos Piloto , Depressão/terapia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Estimulação Magnética Transcraniana , Inflamação/terapia , Biomarcadores
8.
Elife ; 112022 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-35876664

RESUMO

Ammonium (NH4+) is essential to generate the nitrogenous building blocks of life. It gets assimilated via the canonical biosynthetic routes to glutamate and is further distributed throughout metabolism via a network of transaminases. To study the flexibility of this network, we constructed an Escherichia coli glutamate auxotrophic strain. This strain allowed us to systematically study which amino acids serve as amine sources. We found that several amino acids complemented the auxotrophy either by producing glutamate via transamination reactions or by their conversion to glutamate. In this network, we identified aspartate transaminase AspC as a major connector between many amino acids and glutamate. Additionally, we extended the transaminase network by the amino acids ß-alanine, alanine, glycine, and serine as new amine sources and identified d-amino acid dehydrogenase (DadA) as an intracellular amino acid sink removing substrates from transaminase reactions. Finally, ammonium assimilation routes producing aspartate or leucine were introduced. Our study reveals the high flexibility of the cellular amination network, both in terms of transaminase promiscuity and adaptability to new connections and ammonium entry points.


Nitrogen is an essential part of many of the cell's building blocks, including amino acids and nucleotides, which form proteins and DNA respectively. Therefore, nitrogen has to be available to cells so that they can survive and grow. In nature, some microorganisms convert the gaseous form of nitrogen into ammonium, which then acts as the nitrogen source of most organisms, including bacteria, plants and animals. Once cells take up ammonium, it is 'fixed' by becoming part of an amino acid called glutamate, which has a so-called 'amine group' that contains a nitrogen. Glutamate then becomes the central source for passing these amines on to other molecules, distributing nitrogen throughout the cell. This coupling between ammonium fixation and glutamate production evolved over millions of years and occurs in all organisms. However, the complete metabolic network that underlies the distribution of amines remains poorly understood despite decades of research. Furthermore, it is not clear whether ammonium can be fixed in a way that is independent of glutamate. To answer these questions, Schulz-Mirbach et al. used genetic engineering to create a strain of the bacterium E. coli that was unable to make glutamate. These mutant cells could only grow in the presence of certain amino acids, which acted as alternative amine sources. Schulz-Mirbach et al. found that enzymes called transaminases, and one called AspC in particular, were required for the cells to be able to produce glutamate using the amine groups from other amino acids. Notably, Schulz-Mirbach et al. showed that AspC, which had previously been shown to use an amino acid called aspartate as a source of amine groups, is indispensable if the cell is to use the amine groups from other amino acids ­ including histidine, tyrosine, phenylalanine, tryptophan, methionine, isoleucine and leucine. Schulz-Mirbach et al. also discovered that if they engineered the E. coli cells to produce transaminases from other species, the repertoire of molecules that the cells could use as the source of amines to generate glutamate increased. In a final set of experiments, Schulz-Mirbach et al. were able to engineer the cells to fix ammonium by producing aspartate and leucine, thus entirely bypassing the deleted routes of glutamate synthesis. These data suggest that fixing ammonium and distributing nitrogen in E. coli can be very flexible. The results from these experiments may shed light on how cells adapt when there is not a lot of ammonium available. Moreover, this study could advance efforts at metabolic engineering, for example, to create molecules through new pathways or to boost the production of amino acids needed for industrial purposes.


Assuntos
Compostos de Amônio , Escherichia coli , Aminação , Aminas/metabolismo , Aminoácidos/metabolismo , Compostos de Amônio/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Ácido Glutâmico/metabolismo , Transaminases/genética , Transaminases/metabolismo
9.
Signal Image Video Process ; 16(8): 2093-2101, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35261686

RESUMO

The coronavirus (COVID-19) and its global effect have increased the interests of researchers from different disciplines to the medical methods such as immune or convalescent plasma treatment. Immune Plasma algorithm (IPA) that is the first meta-heuristic referencing the steps of the immune plasma treatment as the name implies has been proposed recently and its potential has been investigated. In this study, a pandemic management strategy based on limiting the free movements between regions was modeled and integrated into the workflow of the IPA and a new variant called regional IPA (rIPA) was introduced. For analyzing the contribution of the proposed method, twelve numerical benchmark problems were solved. Also, the performance of the rIPA was investigated by solving a new big data optimization problem that requires minimization of the measurement noise of electroencephalography signals. The results obtained by the rIPA were compared with the fourteen well-known and state-of-art meta-heuristics. Comparative studies showed that managing the relationship between the individuals of the population as in the proposed regional model significantly contributes to the capabilities and rIPA outperforms other meta-heuristics for most of the test cases.

10.
Nat Chem Biol ; 16(5): 538-545, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32042198

RESUMO

Engineering a biotechnological microorganism for growth on one-carbon intermediates, produced from the abiotic activation of CO2, is a key synthetic biology step towards the valorization of this greenhouse gas to commodity chemicals. Here we redesign the central carbon metabolism of the model bacterium Escherichia coli for growth on one-carbon compounds using the reductive glycine pathway. Sequential genomic introduction of the four metabolic modules of the synthetic pathway resulted in a strain capable of growth on formate and CO2 with a doubling time of ~70 h and growth yield of ~1.5 g cell dry weight (gCDW) per mol-formate. Short-term evolution decreased doubling time to less than 8 h and improved biomass yield to 2.3 gCDW per mol-formate. Growth on methanol and CO2 was achieved by further expression of a methanol dehydrogenase. Establishing synthetic formatotrophy and methylotrophy, as demonstrated here, paves the way for sustainable bioproduction rooted in CO2 and renewable energy.


Assuntos
Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Formiatos/metabolismo , Glicina/metabolismo , Metanol/metabolismo , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Dióxido de Carbono/metabolismo , Escherichia coli/genética , Genoma Bacteriano , Engenharia Metabólica/métodos , Redes e Vias Metabólicas , Microrganismos Geneticamente Modificados , Mutação , Biologia Sintética/métodos
11.
IEEE Access ; 8: 220227-220245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-34786298

RESUMO

The recent global health crisis also known as the COVID-19 or coronavirus pandemic has attracted the researchers' attentions to a treatment approach called immune plasma or convalescent plasma once more again. The main idea lying behind the immune plasma treatment is transferring the antibody rich part of the blood taken from the patients who are recovered previously to the critical individuals and its efficiency has been proven by successfully using against great influenza of 1918, H1N1 flu, MERS, SARS and Ebola. In this study, we modeled the mentioned treatment approach and introduced a new meta-heuristic called Immune Plasma (IP) algorithm. The performance of the IP algorithm was investigated in detail and then compared with some of the classical and state-of-art meta-heuristics by solving a set of numerical benchmark problems. Moreover, the capabilities of the IP algorithm were also analyzed over complex engineering optimization problems related with the noise minimization of the electro-encephalography signal measurements. The results of the experimental studies showed that the IP algorithm is capable of obtaining better solutions for the vast majority of the test problems compared to other commonly used meta-heuristic algorithms.

12.
Metab Eng ; 57: 96-109, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31491545

RESUMO

Microbial biosensors are used to detect the presence of compounds provided externally or produced internally. The latter case is commonly constrained by the need to screen a large library of enzyme or pathway variants to identify those that can efficiently generate the desired compound. To address this limitation, we suggest the use of metabolic sensor strains which can grow only if the relevant compound is present and thus replace screening with direct selection. We used a computational platform to design metabolic sensor strains with varying dependencies on a specific compound. Our method systematically explores combinations of gene deletions and identifies how the growth requirement for a compound changes with the media composition. We demonstrate this approach by constructing a set of E. coli glycerate sensor strains. In each of these strains a different set of enzymes is disrupted such that central metabolism is effectively dissected into multiple segments, each requiring a dedicated carbon source. We find an almost perfect match between the predicted and experimental dependence on glycerate and show that the strains can be used to accurately detect glycerate concentrations across two orders of magnitude. Apart from demonstrating the potential application of metabolic sensor strains, our work reveals key phenomena in central metabolism, including spontaneous degradation of central metabolites and the importance of metabolic sinks for balancing small metabolic networks.


Assuntos
Técnicas Biossensoriais , Escherichia coli , Ácidos Glicéricos , Engenharia Metabólica , Redes e Vias Metabólicas , Escherichia coli/genética , Escherichia coli/metabolismo , Ácidos Glicéricos/análise , Ácidos Glicéricos/metabolismo
13.
FEBS J ; 287(1): 160-172, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31436884

RESUMO

The engineering of synthetic metabolic routes can provide valuable lessons on the roles of different biochemical constraints in shaping pathway activity. In this study, we designed and engineered a novel glycerol assimilation pathway in Escherichia coli. While the synthetic pathway was based only on well-characterized endogenous reactions, we were not able to establish robust growth using standard concentrations of glycerol. Long-term evolution failed to improve growth via the pathway, indicating that this limitation was not regulatory but rather relates to fundamental aspects of cellular metabolism. We show that the activity of the synthetic pathway is fully controlled by three key physicochemical constraints: thermodynamics, kinetics and metabolite toxicity. Overcoming a thermodynamic barrier at the beginning of the pathway requires high glycerol concentrations. A kinetic barrier leads to a Monod-like growth dependency on substrate concentration, but with a very high substrate saturation constant. Finally, the flat thermodynamic profile of the pathway enforces a pseudoequilibrium between glycerol and the reactive intermediate dihydroxyacetone, which inhibits growth when the feedstock concentration surpasses 1000 mm. Overall, this study serves to demonstrate the use of synthetic biology to elucidate key design principles of cellular metabolism.


Assuntos
Escherichia coli/metabolismo , Glicerol/metabolismo , Engenharia Metabólica , Biologia Sintética , Fenômenos Bioquímicos , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Cinética , Termodinâmica
14.
Comput Intell Neurosci ; 2019: 5012313, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31065253

RESUMO

Artificial Bee Colony (ABC) algorithm inspired by the complex search and foraging behaviors of real honey bees is one of the most promising implementations of the Swarm Intelligence- (SI-) based optimization algorithms. Due to its robust and phase-divided structure, the ABC algorithm has been successfully applied to different types of optimization problems. However, some assumptions that are made with the purpose of reducing implementation difficulties about the sophisticated behaviours of employed, onlooker, and scout bees still require changes with the more literal procedures. In this study, the ABC algorithm and its well-known variants are powered by adding a new control mechanism in which the decision-making process of the employed bees managing transitions to the dance area is modeled. Experimental studies with different types of problems and analysis about the parallelization showed that the newly proposed approach significantly improved the qualities of the final solutions and convergence characteristics compared to the standard implementations of the ABC algorithms.


Assuntos
Algoritmos , Inteligência Artificial , Comportamento Animal/fisiologia , Redes Neurais de Computação , Animais , Abelhas , Imagem Multimodal , Probabilidade , Fluxo de Trabalho
15.
Biochem J ; 474(23): 3935-3950, 2017 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-29146872

RESUMO

What does it take to convert a living organism into a truly productive biofactory? Apart from optimizing biosynthesis pathways as standalone units, a successful bioengineering approach must bend the endogenous metabolic network of the host, and especially its central metabolism, to support the bioproduction process. In practice, this usually involves three complementary strategies which include tuning-down or abolishing competing metabolic pathways, increasing the availability of precursors of the desired biosynthesis pathway, and ensuring high availability of energetic resources such as ATP and NADPH. In this review, we explore these strategies, focusing on key metabolic pathways and processes, such as glycolysis, anaplerosis, the TCA (tricarboxylic acid) cycle, and NADPH production. We show that only a holistic approach for bioengineering - considering the metabolic network of the host organism as a whole, rather than focusing on the production pathway alone - can truly mold microorganisms into efficient biofactories.


Assuntos
Trifosfato de Adenosina/biossíntese , Ciclo do Ácido Cítrico , Engenharia Metabólica/métodos , NADP/biossíntese , Animais , Humanos , Engenharia Metabólica/tendências
16.
Diagn Interv Radiol ; 23(5): 390-397, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28870884

RESUMO

PURPOSE: Grey matter and white matter changes within the brain are well defined in schizophrenia. However, most studies focused on either grey matter changes or white matter integrity separately; only in limited number of studies these changes were interpreted in the same frame. In addition, the relationship of these findings with clinical variables is not clearly established. Here, we aimed to investigate the grey matter and white matter changes in schizophrenia patients and exhibit the relation of these imaging findings with clinical variables. METHODS: A total of 20 schizophrenia patients and 16 matched healthy controls underwent magnetic resonance imaging to investigate the grey matter and white matter alterations that occur in schizophrenia patients using voxel-based morphometry (VBM) and whole brain voxel-wise analysis of diffusion tensor imaging (DTI) parameters with SPM8, respectively. While the preprocessing steps of VBM were performed with the default parameters of VBM8 toolbox, the preprocessing steps of DTI were carried out using FSL. Additionally, VBM results were correlated with clinical variables. RESULTS: Bilateral insula showed decreased grey matter volume in schizophrenia patients compared with healthy controls (P < 0.01). The opposite contrast did not show a significant difference. Psychiatric scores, duration of illness, and age were not correlated with the decreased grey matter volume of insula in schizophrenia patients. DTI analysis revealed a significant increase in mean, radial, and axial diffusivity, mainly of the fibers of bilateral anterior thalamic radiation and superior longitudinal fasciculus with left predominance, which intersected with bilateral subinsular white matter (P < 0.05). CONCLUSION: Our findings suggest that insula may be the main affected brain region in schizophrenia, which is also well supported by the literature. Our results were independent of disease duration and schizophrenia symptoms. White matter alterations were observed within bilateral anterior thalamic radiation and superior longitudinal fasciculus that intersects with subinsular white matter. Studies with larger sample sizes and more detailed clinical assessments are required to understand the function of insula in the neurobiology of schizophrenia.


Assuntos
Mapeamento Encefálico/métodos , Córtex Cerebral/patologia , Imagem de Tensor de Difusão/métodos , Imageamento por Ressonância Magnética/métodos , Esquizofrenia/patologia , Substância Branca/patologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Masculino , Substância Branca/diagnóstico por imagem
17.
Transgenic Res ; 24(6): 945-53, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26138876

RESUMO

Wax esters are hydrophobic lipids consisting of a fatty acid moiety linked to a fatty alcohol with an ester bond. Plant-derived wax esters are today of particular concern for their potential as cost-effective and sustainable sources of lubricants. However, this aspect is hampered by the fact that the level of wax esters in plants generally is too low to allow commercial exploitation. To investigate whether wax ester biosynthesis can be increased in plants using transgenic approaches, we have here exploited a fusion between two bacterial genes together encoding a single wax ester-forming enzyme, and targeted the resulting protein to chloroplasts in stably transformed tobacco (Nicotiana benthamiana) plants. Compared to wild-type controls, transgenic plants showed both in leaves and stems a significant increase in the total level of wax esters, being eight-fold at the whole plant level. The profiles of fatty acid methyl ester and fatty alcohol in wax esters were related, and C16 and C18 molecules constituted predominant forms. Strong transformants displayed certain developmental aberrations, such as stunted growth and chlorotic leaves and stems. These negative effects were associated with an accumulation of fatty alcohols, suggesting that an adequate balance between formation and esterification of fatty alcohols is crucial for a high wax ester production. The results show that wax ester engineering in transgenic plants is feasible, and suggest that higher yields may become achieved in the near future.


Assuntos
Aciltransferases/metabolismo , Aldeído Oxirredutases/metabolismo , Ésteres/metabolismo , Fusão Gênica/fisiologia , Nicotiana/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Ceras/metabolismo , Aciltransferases/genética , Aldeído Oxirredutases/genética , Fenótipo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Nicotiana/genética , Nicotiana/crescimento & desenvolvimento
18.
Sci Rep ; 5: 11213, 2015 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-26063537

RESUMO

The beta-ketoacyl-ACP synthase II (KASII) is an enzyme in fatty acid biosynthesis, catalyzing the elongation of 16:0-acyl carrier protein (ACP) to 18:0-ACP in plastids. Mutations in KASII genes in higher plants can lead to lethality, which makes it difficult to utilize the gene for lipid metabolic engineering. We demonstrated previously that transient expression of plastid-directed fatty acyl reductases and wax ester synthases could result in different compositions of wax esters. We hypothesized that changing the ratio between C16 (palmitoyl-compounds) and C18 (stearoyl-compounds) in the plastidic acyl-ACP pool by inhibition of KASII expression would change the yield and composition of wax esters via substrate preference of the introduced enzymes. Here, we report that transient inhibition of KASII expression by three different RNAi constructs in leaves of N. benthamiana results in almost complete inhibition of KASII expression. The transient RNAi approach led to a shift of carbon flux from a pool of C18 fatty acids to C16, which significantly increased wax ester production in AtFAR6-containing combinations. The results demonstrate that transient inhibition of KASII in vegetative tissues of higher plants enables metabolic studies towards industrial production of lipids such as wax esters with specific quality and composition.


Assuntos
3-Oxoacil-(Proteína de Transporte de Acila) Sintase/genética , Inativação Gênica , Engenharia Metabólica , Nicotiana/genética , Nicotiana/metabolismo , Proteínas de Plantas/metabolismo , Sintase do Amido/metabolismo , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/antagonistas & inibidores , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/química , Sequência de Bases , Ésteres , Ácidos Graxos/metabolismo , Expressão Gênica , Dados de Sequência Molecular , Folhas de Planta/genética , Folhas de Planta/metabolismo , Interferência de RNA , Alinhamento de Sequência , Transcrição Gênica , Triglicerídeos/metabolismo
19.
Metab Eng ; 25: 103-12, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25038447

RESUMO

In a future bio-based economy, renewable sources for lipid compounds at attractive cost are needed for applications where today petrochemical derivatives are dominating. Wax esters and fatty alcohols provide diverse industrial uses, such as in lubricant and surfactant production. In this study, chloroplast metabolism was engineered to divert intermediates from de novo fatty acid biosynthesis to wax ester synthesis. To accomplish this, chloroplast targeted fatty acyl reductases (FAR) and wax ester synthases (WS) were transiently expressed in Nicotiana benthamiana leaves. Wax esters of different qualities and quantities were produced providing insights to the properties and interaction of the individual enzymes used. In particular, a phytyl ester synthase was found to be a premium candidate for medium chain wax ester synthesis. Catalytic activities of FAR and WS were also expressed as a fusion protein and determined functionally equivalent to the expression of individual enzymes for wax ester synthesis in chloroplasts.


Assuntos
Aldeído Oxirredutases/metabolismo , Cloroplastos/fisiologia , Engenharia Metabólica/métodos , Nicotiana/fisiologia , Folhas de Planta/fisiologia , ATPases Translocadoras de Prótons/metabolismo , Ceras/metabolismo , Aldeído Oxirredutases/genética , Ésteres , Plantas Geneticamente Modificadas/fisiologia , ATPases Translocadoras de Prótons/genética
20.
Gynecol Endocrinol ; 29(5): 465-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23461756

RESUMO

Premenstrual dysphoric disorder (PMDD) is a syndrome related with mood and appetite changes during the late luteal phase. Leptin and insulin are the hormones related to appetite, and leptin may have a role in reproductive functions and mood. Our aim was to determine whether there are differences in serum leptin and insulin levels between women with and without PMDD during the follicular and luteal phases. In this study, 20 women with PMDD and 18 women without PMDD were included. Fasting blood glucose, insulin, leptin, progesterone levels and HOMA-IR were measured in the follicular and luteal phases separately. Repeated-measures analysis of variance revealed significant interactions for serum leptin, insulin and HOMA-IR levels between the diagnosis of PMDD and menstrual phases (F = 5.4, p = 0.025; F = 5.4, p = 0.026; and F = 4.7, p = 0.036, respectively). A significant correlation was found between progesterone and insulin levels in subjects without PMDD in the luteal phase (r = 0.58, p = 0.01). Whether the alterations in serum leptin and insulin are related with the changes of appetite and mood in PMDD or secondary to other factors should be clarified.


Assuntos
Insulina/sangue , Leptina/sangue , Ciclo Menstrual/sangue , Síndrome Pré-Menstrual/sangue , Adulto , Feminino , Humanos
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