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Both trio and population designs are popular study designs for identifying risk genetic variants in genome-wide association studies (GWASs). The trio design, as a family-based design, is robust to confounding due to population structure, whereas the population design is often more powerful due to larger sample sizes. Here, we propose KnockoffHybrid, a knockoff-based statistical method for hybrid analysis of both the trio and population designs. KnockoffHybrid provides a unified framework that brings together the advantages of both designs and produces powerful hybrid analysis while controlling the false discovery rate (FDR) in the presence of linkage disequilibrium and population structure. Furthermore, KnockoffHybrid has the flexibility to leverage different types of summary statistics for hybrid analyses, including expression quantitative trait loci (eQTL) and GWAS summary statistics. We demonstrate in simulations that KnockoffHybrid offers power gains over non-hybrid methods for the trio and population designs with the same number of cases while controlling the FDR with complex correlation among variants and population structure among subjects. In hybrid analyses of three trio cohorts for autism spectrum disorders (ASDs) from the Autism Speaks MSSNG, Autism Sequencing Consortium, and Autism Genome Project with GWAS summary statistics from the iPSYCH project and eQTL summary statistics from the MetaBrain project, KnockoffHybrid outperforms conventional methods by replicating several known risk genes for ASDs and identifying additional associations with variants in other genes, including the PRAME family genes involved in axon guidance and which may act as common targets for human speech/language evolution and related disorders.
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Transtorno do Espectro Autista , Estudo de Associação Genômica Ampla , Desequilíbrio de Ligação , Locos de Características Quantitativas , Estudo de Associação Genômica Ampla/métodos , Humanos , Transtorno do Espectro Autista/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Simulação por Computador , Modelos GenéticosRESUMO
Smartphone adaptation in society has been progressing at a very high speed. Having the ability to run on a vast variety of devices, much of the user base possesses an Android phone. Its popularity and flexibility have played a major role in making it a target of different attacks via malware, causing loss to users, both financially and from a privacy perspective. Different malware and their variants are emerging every day, making it a huge challenge to come up with detection and preventive methodologies and tools. Research has spawned in various directions to yield effective malware detection mechanisms. Since malware can adopt different ways to attack and hide, accurate analysis is the key to detecting them. Like any usual mobile app, malware requires permission to take action and use device resources. There are 235 total permissions that the Android app can request on a device. Malware takes advantage of this to request unnecessary permissions, which would enable those to take malicious actions. Since permissions are critical, it is important and challenging to identify if an app is exploiting permissions and causing damage. The focus of this article is to analyze the identified studies that have been conducted with a focus on permission analysis for malware detection. With this perspective, a systematic literature review (SLR) has been produced. Several papers have been retrieved and selected for detailed analysis. Current challenges and different analyses were presented using the identified articles.
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Segurança Computacional , Aplicativos Móveis , Smartphone , PrivacidadeRESUMO
This paper provides a new solution to identify the internal forces of segmental tunnel linings by combining laser scanning and hybrid structural analysis. First, a hybrid structural analysis method for quantifying the internal forces based on displacement monitoring is established, which requires comprehensive displacement monitoring with high precision and a complete trace history. Motivated by the development of laser scanning, two remedial solutions are proposed for typically insufficient engineering conditions, i.e., lack of displacement developing process and poor accuracy of measurements, which is highlighted in this paper. Therefore, with the help of remedial solutions, the structural analysis is able to be adopted with the application of laser scanning. The tool for developing remedial solutions is the first-order theory of slender circular arches. Virtual tests, based on a calibrated finite element model, were performed to verify the feasibility of the presented hybrid analysis and remedial solutions. In addition, parametric analyses were conducted to study the error propagation from laser scanning to the results of hybrid analysis. The resolution and measurement noise of laser scanning were investigated and discussed. On this basis, advice on combining laser scanning and hybrid structural analysis is proposed. Finally, on-site application of the hybrid analysis on an actual tunnel is presented and discussed.
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With the popularity of Android, malware detection and family classification have also become a research focus. Many excellent methods have been proposed by previous authors, but static and dynamic analyses inevitably require complex processes. A hybrid analysis method for detecting Android malware and classifying malware families is presented in this paper, and is partially optimized for multiple-feature data. For static analysis, we use permissions and intent as static features and use three feature selection methods to form a subset of three candidate features. Compared with various models, including k-nearest neighbors and random forest, random forest is the best, with a detection rate of 95.04%, while the chi-square test is the best feature selection method. After using feature selection to explore the critical static features contained in this dataset, we analyzed a subset of important features to gain more insight into the malware. In a dynamic analysis based on network traffic, unlike those that focus on a one-way flow of traffic and work on HTTP protocols and transport layer protocols, we focused on sessions and retained protocol layers. The Res7LSTM model is then used to further classify the malicious and partially benign samples detected in the static detection. The experimental results show that our approach can not only work with fewer static features and guarantee sufficient accuracy, but also improve the detection rate of Android malware family classification from 71.48% in previous work to 99% when cutting the traffic in terms of the sessions and protocols of all layers.
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Spliceosomal Prp38 proteins contain a conserved amino-terminal domain, but only higher eukaryotic orthologs also harbor a carboxy-terminal RS domain, a hallmark of splicing regulatory SR proteins. We show by crystal structure analysis that the amino-terminal domain of human Prp38 is organized around three pairs of antiparallel α-helices and lacks similarities to RNA-binding domains found in canonical SR proteins. Instead, yeast two-hybrid analyses suggest that the amino-terminal domain is a versatile protein-protein interaction hub that possibly binds 12 other spliceosomal proteins, most of which are recruited at the same stage as Prp38. By quantitative, alanine surface-scanning two-hybrid screens and biochemical analyses we delineated four distinct interfaces on the Prp38 amino-terminal domain. In vitro interaction assays using recombinant proteins showed that Prp38 can bind at least two proteins simultaneously via two different interfaces. Addition of excess Prp38 amino-terminal domain to in vitro splicing assays, but not of an interaction-deficient mutant, stalled splicing at a precatalytic stage. Our results show that human Prp38 is an unusual SR protein, whose amino-terminal domain is a multi-interface protein-protein interaction platform that might organize the relative positioning of other proteins during splicing.
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Subunidades Proteicas/química , Precursores de RNA/química , Splicing de RNA , RNA Mensageiro/química , Proteínas de Saccharomyces cerevisiae/química , Spliceossomos/química , Sequência de Aminoácidos , Animais , Arabidopsis/genética , Arabidopsis/metabolismo , Sítios de Ligação , Cristalografia por Raios X , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Precursores de RNA/genética , Precursores de RNA/metabolismo , Fatores de Processamento de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Spliceossomos/genética , Spliceossomos/metabolismoRESUMO
The function of inner membrane protein YciB in Escherichia coli has not been identified. In this study, the membrane topology of the protein that contains five transmembrane domains was clarified. YciB was found to interact with various proteins involved in cell elongation and cell division using a bacterial two-hybrid system. It was also found that the deletion mutant of yciB is susceptible to the low osmolarity. These observations together with previous reports indicate that YciB is involved in synthesis of the cell envelope by interacting with cell elongation and cell division complexes.
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Divisão Celular/fisiologia , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/fisiologia , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Domínios e Motivos de Interação entre Proteínas/genética , Deleção de Sequência/fisiologia , Escherichia coli , Técnicas do Sistema de Duplo-HíbridoRESUMO
Objective: This is a comprehensive overview of long-term cancer survival in Zhejiang Province, China. Hybrid analysis, a combination of cohort and period analysis, has been proposed to derive up-to-date cancer survival estimates. Using this approach, we aimed to timely and accurately analyze the 5-year relative survival (RS) and net survival (NS) in cancer registries of Zhejiang Province, China. Methods: A total of 255,725 new cancer cases diagnosed during 2013-2017 were included in 14 cancer registries in Zhejiang Province, China, with a follow-up on vital status until the end of 2019. The hybrid analysis was used to calculate the 5-year RS and 5-year NS during 2018-2019 for overall and stratifications by sex, cancer type, region, and age at diagnosis. Results: During 2018-2019, the age-standardized 5-year RS and NS for overall cancer in Zhejiang was 47.5% and 48.6%, respectively. The age-standardized 5-year RS for cancers of women (55.4%) was higher than that of men (40.0%), and the rate of urban areas (49.7%) was higher than that of rural areas (43.1%). The 5-year RS declined along with age, from 84.4% for ages <45 years to 23.7% for ages >74 years. Our results of the RS and NS showed the similar trend and no significant difference. The top five cancers with top age-standardized 5-year RS were thyroid cancer (96.0%), breast cancer (84.3%), testicular cancer (79.9%), prostate cancer (77.2%), and bladder cancer (70.6%), and the five cancers with the lowest age-standardized 5-year RS were pancreatic cancer (6.0%), liver cancer (15.6%), gallbladder cancer (17.1%), esophageal cancer (22.7%), and leukemia (31.0%). Conclusions: We reported the most up-to-date 5-year cancer RS and NS in Zhejiang Province, China for the first time, and found that the 5-year survival for cancer patients in Zhejiang during 2018-2019 was relatively high. The population-based cancer registries are recognized as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems.
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The integration of renewable energy sources can be supported by the digitalization of energy systems, which increase dependability and lower costs of energy production and consumption. However, the energy digitalization support energy infrastructures and technologies currently in place are insufficient. This research presented the study results by using the generalized least square estimates (GLS) model and the international sample of China regions from 2003 to 2017. Main results of the dynamic fixed effect (DFE) estimator for the autoregressive distributed lag (ARDL) method, establishing ES goals for lowering energy consumption and pollution emission fosters a country's renewable energy business sector's digital transformation in the short term, while encouraging the use of renewable energy sources fosters a country's long-term digitalization efforts. Based on this, the direct effects and dynamic effects of digitalization and financial development on environmental are explored, respectively, using the panel data regression model and panel vector autoregression (PVAR) model. The threshold regression model is then used to examine the two parameters' threshold effects on eco-efficiency. An accurate estimate of the resource consumption in smart factories is made possible by the digital twin that is created using the product's and its attributes as well as manufacturing data. The results suggests the future directions for the associated stakeholders.
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Desenvolvimento Econômico , Energia Renovável , Poluição Ambiental/análise , Tecnologia , China , Dióxido de Carbono/análiseRESUMO
It is often unclear how genetic variation translates into cellular phenotypes, including how much of the coding variation can be recovered in the proteome. Proteogenomic analyses of heterogenous cell lines revealed that the genetic differences impact mostly the abundance and stoichiometry of protein complexes, with the effects propagating post-transcriptionally via protein interactions onto other subunits. Conversely, large scale binary interaction analyses of missense variants revealed that loss of interaction is widespread and caused by about 50% disease-associated mutations, while deep scanning mutagenesis of binary interactions identified thousands of interaction-deficient variants per interaction. The idea that phenotypes arise from genetic variation through protein-protein interaction is therefore substantiated by both forward and reverse interaction proteomics. With improved methodologies, these two approaches combined can close the knowledge gap between nucleotide sequence variation and its functional consequences on the cellular proteome.
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Mapeamento de Interação de Proteínas , Proteômica , Variação Genética , Mutagênese , Mutação , Mapeamento de Interação de Proteínas/métodos , Proteoma/genética , Proteoma/metabolismo , Proteômica/métodosRESUMO
The phage λ rexA and rexB genes are expressed from the P RM promoter in λ lysogens along with the cI repressor gene. RexB is also expressed from a second promoter, P LIT, embedded in rexA. The combined expression of rexA and rexB causes Escherichia coli to be more ultraviolet (UV) sensitive. Sensitivity is further increased when RexB levels are reduced by a defect in the P LIT promoter, thus the degree of sensitivity can be modulated by the ratio of RexA/RexB. Expression of the phage λ ren gene rescues this host UV sensitive phenotype; Ren also rescues an aberrant lysis phenotype caused by RexA and RexB. We screened an E. coli two-hybrid library to identify bacterial proteins with which each of these phage proteins physically interact. The results extend previous observations concerning λ Rex exclusion and show the importance of E. coli electron transport and sulfur assimilation pathways for the phage.
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Foot rot disease caused by Phytophthora capsici is a serious threat to black pepper cultivation in India and globally. High diversity exists among the Phytophthora isolates of black pepper and hence detailed investigations of their morphology and phylogenetic taxonomy were carried out in the present study. In order to resolve the diversity, 182 isolates of Phytophthora, collected from different black pepper-growing tracts of South India during 1998-2013 and maintained in the National Repository of Phytophthora at ICAR-Indian Institute of Spices Research, Kozhikode, were subjected to morphological, molecular and phylogenetic characterization. Morphologically all the isolates were long pedicellate with umbellate/simple sympodial sporangiophores and papillate sporangia with l/b ranging from 1.63 to 2.55 µm. Maximum temperature for the growth was ~ 34 °C. Chlamydospores were observed in "tropicalis" group, whereas they were absent in "capsici" group. Initial molecular studies using internal transcribed spacer (ITS) marker gene showed two clear cut lineages-"capsici-like" and "tropicalis-like" groups among them. Representative isolates from each group were subjected to host differential test, multilocus sequence typing (MLST) and phylogeny studies. MLST analysis of seven nuclear genes (60S ribosomal protein L10, beta-tubulin, elongation factor 1 alpha, enolase, heat shock protein 90, 28S ribosomal DNA and TigA gene fusion protein) clearly delineated black pepper Phytophthora isolates into two distinct species-P. capsici and P. tropicalis. On comparing with type strains from ATCC, it was found that the type strains of P. capsici and P. tropicalis differed from black pepper isolates in their infectivity on black pepper. The high degree of genetic polymorphism observed in black pepper Phytophthora isolates is an indication of the selection pressure they are subjected to in the complex habitat which ultimately may lead to speciation. So based on the extensive analysis, it is unambiguously proved that the foot rot disease of black pepper in India is predominantly caused by two species of Phytophthora, viz. P. capsici and P. tropicalis. Presence of multiple species of Phytophthora in the black pepper agro-ecosystem warrants a revisit to the control strategy being adopted for managing this serious disease. The silent molecular evolution taking place in such an ecological niche needs to be critically studied for the sustainable management of foot rot disease.
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Phytophthora , Piper nigrum , Ecossistema , Humanos , Tipagem de Sequências Multilocus , Filogenia , Piper nigrum/microbiologia , Doenças das Plantas/microbiologia , IrmãosRESUMO
In this work, we introduce, justify and demonstrate the Corrective Source Term Approach (CoSTA)-a novel approach to Hybrid Analysis and Modeling (HAM). The objective of HAM is to combine physics-based modeling (PBM) and data-driven modeling (DDM) to create generalizable, trustworthy, accurate, computationally efficient and self-evolving models. CoSTA achieves this objective by augmenting the governing equation of a PBM model with a corrective source term generated using a deep neural network. In a series of numerical experiments on one-dimensional heat diffusion, CoSTA is found to outperform comparable DDM and PBM models in terms of accuracy - often reducing predictive errors by several orders of magnitude - while also generalizing better than pure DDM. Due to its flexible but solid theoretical foundation, CoSTA provides a modular framework for leveraging novel developments within both PBM and DDM. Its theoretical foundation also ensures that CoSTA can be used to model any system governed by (deterministic) partial differential equations. Moreover, CoSTA facilitates interpretation of the DNN-generated source term within the context of PBM, which results in improved explainability of the DNN. These factors make CoSTA a potential door-opener for data-driven techniques to enter high-stakes applications previously reserved for pure PBM.
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Redes Neurais de Computação , FísicaRESUMO
Fungal mating-type loci (MAT) encode transcription factors (TFs) MAT1-1-1 and MAT1-2-1, which govern sexual reproduction as well as other developmental processes. In Penicillium chrysogenum, the major producer of the beta-lactam antibiotic penicillin, a recent chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis identified 254 genes as direct targets of MAT1-1-1, many of which encode thus far uncharacterized proteins. Here, we characterized one of the major targets of MAT1-1-1, the tom1 gene, which encodes a protein highly conserved within the group of Eurotiomycetes fungi. Using fluorescence microscopy, we demonstrated binding of MAT1-1-1 to the tom1 promoter by reporter gene analysis. Extensive electrophoretic mobility shift assays (EMSAs) further showed that the promoter sequence of tom1 is bound in vitro by both MAT1-1-1 and MAT1-2-1. This indicated an interaction between the two TFs, which was verified by yeast two-hybrid analysis. The sequence of tom1 carries a nuclear localization sequence, and indeed its nuclear localization was verified by fluorescence microscopy. The in vivo function of tom1 was investigated using tom1 deletion strains, as well as a complementing strain where the wild-type tom1 gene was reintroduced. We found a clear sporulation defect in the deletion strain, which became more evident when the fungi were grown at an elevated temperature of 31°C.
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Quality Protein Popcorn (QPP) BC2F5 inbred lines were produced through an interpopulation breeding system between Quality Protein Maize dent (QPM) and elite popcorn germplasm. In 2019, five QPP F1 hybrids were selected for further evaluation due to superior agronomics, endosperm protein quality, and popping quality traits. Though these BC2F5 QPP hybrids were phenotypically similar to their popcorn parents, the QPP cultivars conveyed slightly inferior popping characteristics when compared to the original popcorn germplasm. The objective of this study was twofold. First, BC2F5 inbred lines were crossed to their popcorn parents and BC3F4 inbred lines were produced for hybridization to test the agronomic, protein, and popping trait effects from an additional QPP by popcorn backcross. Second, BC2- and BC3-hybrids were simultaneously evaluated alongside ConAgra Brands® elite cultivars and ranked for potential commercialization in the spring of 2020. These 10 QPP hybrids were grown alongside five ConAgra Brands® elite popcorn cultivars in three locations and agronomic, protein quality, and popping quality traits were evaluated. Significant improvements in popcorn quality traits were observed in the QPP BC3 cultivars compared to their BC2 counterparts, and yield averages were significantly lower in BC3-derived QPP hybrids compared to the BC2 population. Protein quality traits were not significantly different between QPP backcrossing populations and significantly superior to ConAgra elite popcorn varieties. Utilizing a previously published ranking system, six QPP hybrids, three from the BC2F5 population and three from the BC3F4 population, were evaluated as candidates for final selection. The successful evaluation and ranking system methodology employed is transferable to other hybrid production and testing programs. Incorporating this analysis with concurrent sensory studies, two QPP hybrids were chosen as premier cultivars for potential commercialization.
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Plant organs that are exposed to continuous unilateral light reach in the steady-state a photogravitropic bending angle that results from the mutual antagonism between the photo- and gravitropic responses. To characterize the interaction between the two tropisms and their quantitative relationship we irradiated seedlings of Arabidopsis thaliana that were inclined at various angles and determined the fluence rates of unilateral blue light required to compensate the gravitropism of the inclined hypocotyls. We found the compensating fluence rates to increase with the tangent of the inclination angles (0° < γ < 90° or max. 120°) and decrease with the cotangent (90°< γ < 180° or max. 120°of the inclination angles. The tangent dependence became also evident from analysis of previous data obtained with Avena sativa and the phycomycete fungus, Phycomyces blakesleeanus. By using loss-of function mutant lines of Arabidopsis, we identified EHB1 (enhanced bending 1) as an essential element for the generation of the tangent and cotangent relationships. Because EHB1 possesses a C2-domain with two putative calcium binding sites, we propose that the ubiquitous calcium dependence of gravi- and phototropism is in part mediated by Ca2+-bound EHB1. Based on a yeast-two-hybrid analysis we found evidence that EHB1 does physically interact with the ARF-GAP protein AGD12. Both proteins were reported to affect gravi- and phototropism antagonistically. We further showed that only AGD12, but not EHB1, interacts with its corresponding ARF-protein. Evidence is provided that AGD12 is able to form homodimers as well as heterodimers with EHB1. On the basis of these data we present a model for a mechanism of early tropism events, in which Ca2+-activated EHB1 emerges as the central processor-like element that links the gravi- and phototropic transduction chains and that generates in coordination with NPH3 and AGD12 the tangent / cotangent algorithm governing photogravitropic equilibrium.
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Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Gravitropismo/genética , Fototropismo/genética , Phycomyces/fisiologia , Arabidopsis/genética , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/metabolismo , Avena/genética , Avena/fisiologia , Proteínas Ativadoras de GTPase/metabolismo , Hipocótilo/metabolismo , Luz , Phycomyces/genética , Plântula/genética , Plântula/fisiologia , Plântula/efeitos da radiaçãoRESUMO
Popcorn varieties are agronomically sub-optimal and genetically limited compared to other maize subspecies. To increase genetic diversity and improve popcorn agronomics, dent germplasm has been introduced to popcorn with limited success and generally, major loss of popping. Between 2013 and 2018, 12 Quality Protein Popcorn (QPP) inbreds containing Quality Protein Maize (QPM) and popcorn germplasm were produced that maintained popping while carrying the opaque-2 allele conferring elevated kernel lysine. This is an opportune trait in the growing market for healthier snacks and a model for mining QPM traits into popcorn. We crossed QPP inbreds to explore the effects of heterosis on popcorn protein, popping quality, and plant agronomics and selected hybrids for further production. To rank and intermediately prescreen hybrids, we utilized a novel hybrid-ranking model adapted from a rank summation index while examining the inbred general combining ability and hybrid specific combining ability estimates for all traits. We observed a biological manifestation of heterosis by categorizing hybrids by pedigree that resulted in a stepwise progression of trait improvement. These results corroborated our hybrid selection and offered insight in basic heterosis research. Estimates for popcorn quality and agronomic trait covariances also suggest the synergistic introgression of highly vitreous dent maize (QPM) into popcorn, providing a likely explanation for the successfully maintained vitreous endosperm, protein quality and popping traits in line with a remodeled proteome. QPP hybrids maintained improved amino acid profiles although different popping methods variably affected popcorn's protein bound and free amino acid levels. This preliminary screening of QPP hybrids is enabling further quantitative selection for large-scale, complex trait comparison to currently marketed elite popcorn varieties.
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BACKGROUND: The present study aimed to identify and prioritize strategies for medical tourism improvement in the Social Security Organization (SSO) of Iran. METHODS: Using Delphi method in the first step, we identify strengths, weaknesses, opportunities and threats that Social Security Organization of Iran faces in medical tourism during 2017-2018. In the second step we interviewed 100 medical and tourism experts to identify proper strategies using SWOT method and finally priori-tize strategies through the Analytic Hierarchy Process (AHP) by using Expert Choice software. RESULTS: The application of SWOT technique indicated that the dominant strategy for the Iranian SSO should be conservative. It should overcome its internal weaknesses and exploit its external opportunities. The Iranian Social Security Organization should arrange appropriate marketing in target countries, invest in international medical/hospital standards, boost the communicative competence of personnel in SSO hospitals and create multilingual web-based information to introduce the capabilities and costs of the hospitals. CONCLUSION: Since the SSO's weaknesses are more prominent than its strengths, thus SSO should plan to reduce its weaknesses to boost medical tourism. For this purpose, SSO should design coherent plans for attract medical tourists to the organization's hospitals, attempt to upgrade hospital and medical centers standards, train the medical staff regarding linguistic and communicative skills, and run a user-friendly website to introduce its medical capabilities.
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Prohibitins (PHBs) are evolutionarily conserved mitochondrial integral membrane proteins, shown to regulate mitochondrial structure and function, and can be classified into PHB1 and PHB2. PHB1 and PHB2 have been shown to interact with each other, and form heterodimers in mitochondrial inner membrane. Plasmodium falciparum has orthologues of PHB1 and PHB2 in its genome, and their role is unclear. Here, by homology modelling and yeast two-hybrid analysis, we show that putative Plasmodium PHBs (Pf PHB1 and Pf PHB2) interact with each other, which suggests that they could form supercomplexes of heterodimers in Plasmodium, the functional form required for optimum mitochondrial function.
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Proteínas de Membrana/química , Plasmodium falciparum/química , Proteínas de Protozoários/química , Proteínas Repressoras/química , Mitocôndrias/metabolismo , Modelos Moleculares , Plasmodium falciparum/genética , Proibitinas , Conformação Proteica , Multimerização Proteica , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae , Técnicas do Sistema de Duplo-HíbridoRESUMO
In this study, PVF11 was selected among 20 candidate pathogenesis-related genes in Burkholderia glumae based on its effect on virulence to rice. PVF11 was found to interact with several plant defense-related WRKY proteins as evidenced through yeast-two hybrid analysis (Y2H). Moreover, PVF11 showed interactions with abiotic and biotic stress response-related rice proteins, as shown by genome-wide Y2H screening employing PVF11 and a cDNA library from B. glumae-infected rice. To confirm the effect of PVF11 on B. glumae virulence, in planta assays were conducted at different stages of rice growth. As a result, a PVF11-defective mutant showed reduced virulence in rice seedlings and stems but not in rice panicles, indicating that PVF11 involvement in B. glumae virulence in rice is stage-dependent.
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Cyclin-dependent kinase 5 (CDK5) is an unusual CDK whose function has been implicated in protecting the central nervous system (CNS) from oxidative damage. However, there have been few studies of CDK5 in insects. In this study, we identified the AccCDK5 gene from Apis cerana cerana and investigated its role in oxidation resistance. We found that AccCDK5 is highly conserved across species and contains conserved features of the CDK5 family. The results of qPCR analysis indicated that AccCDK5 is highly expressed during the larval and pupal stages and in the adult head and muscle. We further observed that AccCDK5 is induced by several environmental oxidative stresses. Moreover, the overexpression of the AccCDK5 protein in E. coli enhances the resistance of the bacteria to oxidative stress. The activation of CDK5 requires binding to its activator. Therefore, we also identified and cloned cyclin-dependent kinase 5 regulatory subunit 1, which we named AccCDK5r1, from Apis cerana cerana. AccCDK5r1 contains a conserved cell localization targeting domain as well as binding and activation sites for CDK5. Yeast two-hybrid analysis demonstrated the interaction between AccCDK5 and AccCDK5r1. The expression patterns of the two genes were similar after stress treatment. Collectively, these results suggest that AccCDK5 plays a pivotal role in the response to oxidative stresses and that AccCDK5r1 is a potential activator of AccCDK5.