2,399,507 research outputs found
Comparative analysis of Mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and an apparent absence of selective constraints.
Full text linkContains fulltext :
110619.pdf (Publisher’s version ) (Open Access)Mycobacterium tuberculosis complex (MTBC) genomes contain 2 large gene families termed pe and ppe. The function of pe/ppe proteins remains enigmatic but studies suggest that they are secreted or cell surface associated and are involved in bacterial virulence. Previous studies have also shown that some pe/ppe genes are polymorphic, a finding that suggests involvement in antigenic variation. Using comparative sequence analysis of 18 publicly available MTBC whole genome sequences, we have performed alignments of 33 pe (excluding pe_pgrs) and 66 ppe genes in order to detect the frequency and nature of genetic variation. This work has been supplemented by whole gene sequencing of 14 pe/ppe (including 5 pe_pgrs) genes in a cohort of 40 diverse and well defined clinical isolates covering all the main lineages of the M. tuberculosis phylogenetic tree. We show that nsSNP's in pe (excluding pgrs) and ppe genes are 3.0 and 3.3 times higher than in non-pe/ppe genes respectively and that numerous other mutation types are also present at a high frequency. It has previously been shown that non-pe/ppe M. tuberculosis genes display a remarkably low level of purifying selection. Here, we also show that compared to these genes those of the pe/ppe families show a further reduction of selection pressure that suggests neutral evolution. This is inconsistent with the positive selection pressure of "classical" antigenic variation. Finally, by analyzing such a large number of genes we were able to detect large differences in mutation type and frequency between both individual genes and gene sub-families. The high variation rates and absence of selective constraints provides valuable insights into potential pe/ppe function. Since pe/ppe proteins are highly antigenic and have been studied as potential vaccine components these results should also prove informative for aspects of M. tuberculosis vaccine design
czs108/PE-Packer: v1.0.0-beta
No full textPE-Packer is a simple packer for Windows PE files. The new PE file after packing can obstruct the process of reverse engineering.
It will do the following things when packing a PE file:
Transforming the original import table.
Encrypting sections.
Clearing section names.
Installing the shell-entry.
When running a packed PE file, the shell-entry will decrypt and load the original program as follows:
Decrypting sections.
Initializing the original import table.
Relocation.
Warning
This project is just a demo for beginners to study Windows PE Format and Assembly Language. It still has some compatibility problems and bugs that cannot be used in practice
PE-Microphallus_annotated_transcriptome
No full textFasta formatted annotated transcriptome for PE-Microphallus The assembly was generated using Trinity, followed by TransDecoder, then CD-HIT-EST. The transcriptome was annotated using blastx and Blast2GO
COMPARISON OF IN VITRO PRE-ECLAMPSIA (PE) CELL MODELS WITH PE PLACENTAL TISSUE
No full textObjectives: We induced hypoxia and oxidative stress (OS) in cytotrophoblasts
(CTB) from control placentae to mimic the characteristics of preeclampsia
(PE). For validation we compared the gene and protein
expression of established PE biomarkers between the cell models and PE
placentae.
Methods: CTB isolated from healthy term placentae (n¼2) were cultured
either under normoxic (5% pCO2;21% pO2;24h), hypoxic (5% pCO2;1.5%
pO2;24h) or OS (consecutive 6h-intervals of normoxia and hypoxia until
24h) conditions. mRNA abundances of PE biomarkers (Table1) were analysed
by qRT-PCR in the cell models and PE placentae (n¼12). Additionally,
the secretion of sFlt1 and PlGF was determined by ELISA in cell culture
supernatants. Statistical analysis was performed using unpaired t-test.
Results: The cell models recapitulated important pathophysiological
changes occurring in PE (Table1) including the upregulation of sFlt1 which
was also observed in PE placentae. Interestingly, in the cell models the
sFlt1/PlGF ratio was above the clinically applied cutoff value of 38 for
hypoxic (77.3±35.2) and OS (124±88.3), but <38 for normoxic (19.4±16)
conditions.
nm-not measured
Conclusion: The established cell models are mimicking important characteristics
of PE. The sFlt1/PlGF ratio obtained in cell models is in agreement
with reports proposing sFlt1/PlGF as predictive diagnostic marker for
PE. Thus, hypoxia and OS induced in primary CTB can serve as suitable
models to study the detailed mechanisms of PE
PE-for-health in Maltese schools: supporting teachers’ professional development
No full textThere have been many interpretations of health within the Physical Education (PE) curriculum over the years and its implementation has encountered various challenges. An evidence-based approach to health learning in PE has been called for to investigate how PE teachers can be supported through effective continuous professional development (CPD) to address increasing health expectations. Underpinned by an interpretivist paradigm, this three-phase qualitative study focusses on health within PE in Malta and on PE teachers’ CPD in this area. Specifically, it explores the expectations of PE with regard to health and how physical educators are supported through innovative and effective PE-CPD to meet health expectations. In phase 1, expectations of PE with regard to health were investigated. This involved conducting 31 interviews with policy makers, PE officials and teacher educators, and PE teachers. The findings revealed increasing health expectations of PE and, although health outcomes were accepted by all stakeholders, there was lack of clarity on how these were to be achieved. PE teachers were disengaged from policy and curricular developments and the broad range of outcomes associated with PE hindered the implementation of health learning within the subject. The absence of health-related CPD and research in this field were identified as gaps within the Maltese education system. Informed by the phase 1 findings and relevant PE-CPD literature, phase 2 involved designing, implementing and evaluating PE-for-health professional development (PD) with 6 volunteer PE teachers. The PE-for-health PD framework was tailor-made to suit the range of learning needs of the PE teachers and to support them in meeting health expectations. Subsequently, in phase 3, the teachers’ experiences of and responses to the PD were investigated through a focus group and individual interviews. It was revealed that the PE teachers considered the PD to be innovative and evolutionary. They welcomed key features of the process, such as its flexibility, sustained approach and collaborative nature which encouraged reflection and professional dialogue. The PD supported the PE teachers' personal and professional growth, provided a space for their voices to be heard, led them to make changes to their practices and empowered them to take the lead as health advocates in raising the health agenda in their schools. Engagement of the PE teachers beyond the PD process however, proved challenging.The findings suggest implications for policy and practice relating to PE-CPD provision and health learning in Maltese schools. Health expectations and outcomes should be taken more seriously and health should be given more prominence within PE in Malta. Effective health learning in PE in Maltese schools is dependent on teachers being supported with relevant, engaging PE-CPD. A redesign of PE-CPD provision in Malta, involving specialist pathways and including a focus on health learning and effective facilitation, is called for. Meaningful PE-CPD will help ensure that PE teachers are actively and strategically engaged to challenge the status quo of the subject and achieve PE-for-health expectations. </p
A socio-ecological approach to understanding adolescent girls' engagement and experiences in the PE environment : a case study design
Full text linkAdolescence is known to be a period of increased risk for the development of unhealthy behaviours such as physical inactivity (Currie et al., 2011). Low physical activity (PA) levels are especially noted in girls, who typically engage in less PA than boys throughout the teenage years (Whitehead and Biddle 2008). In Scotland, evidence suggests there is a significant decline in PA among adolescent girls, with only 41% of 13−15 year olds achieving the current recommendations, compared with 56% of 11−12 year olds (Scottish Executive, 2011). In addition, a proportion of girls are not engaging with school PE classes (Niven et al., 2014; Kirby et al., 2012). In order to understand more about how and why this decline exists, a sample of 20 ‘disengaged’ 12−13-year-old girls (second year of secondary school) were recruited from four case study schools in Scotland. This study aims to explore the interaction between the social and physical environment, and how these affect disengaged girls’ experiences and engagement in PE. Girls were categorised as ‘disengaged’ from PE if they did not participate regularly and reported negative emotions about the subject. Girls took part in in-depth interviews to explore their experiences and engagement in PE. The theoretical framework is based on Welks (1999) Youth Physical Activity Promotion model (YPAP), a socio-ecological approach which conceptualises the influential correlates of PA as: individual-level predisposing and enabling factors, including personal attributes and environmental variables and reinforcing (social) factors. This model was applied within a Scottish education context to understand the importance of each component and also the interaction between these and the influence that one may have on another. The results indicate that although the type of activity offered in PE is important, it appears that perceptions of competence and the social environment these were delivered in, such as single-sex classes, had more of an influence on girls’ engagement in PE. For this group of Scottish adolescent girls, the wider psychosocial environment in which PE takes place may have a greater impact on levels of enjoyment and participation than the PA itself.Peer reviewe
Empowerment of 15-Lipoxygenase Catalytic Competence in Selective Oxidation of Membrane ETE-PE to Ferroptotic Death Signals, HpETE-PE
No full textsn2-15-Hydroperoxy-eicasotetraenoyl-phosphatidylethanolamines
(sn2-15-HpETE-PE) generated by mammalian 15-lipoxygenase/phosphatidylethanolamine
binding protein-1 (15-LO/PEBP1) complex is a death signal in a recently
identified type of programmed cell demise, ferroptosis. How the enzymatic
complex selects sn2-ETE-PE as the substrate among 1 of ∼100 total oxidizable
membrane PUFA phospholipids is a central, yet unresolved question.
To unearth the highly selective and specific mechanisms of catalytic
competence, we used a combination of redox lipidomics, mutational
and computational structural analysis to show they stem from (i) reactivity
toward readily accessible hexagonally organized membrane sn2-ETE-PEs, (ii) relative preponderance of sn2-ETE-PE
species vs other sn2-ETE-PLs, and (iii) allosteric
modification of the enzyme in the complex with PEBP1. This emphasizes
the role of enzymatic vs random stochastic free radical reactions
in ferroptotic death signaling
Empowerment of 15-Lipoxygenase Catalytic Competence in Selective Oxidation of Membrane ETE-PE to Ferroptotic Death Signals, HpETE-PE
No full textsn2-15-Hydroperoxy-eicasotetraenoyl-phosphatidylethanolamines
(sn2-15-HpETE-PE) generated by mammalian 15-lipoxygenase/phosphatidylethanolamine
binding protein-1 (15-LO/PEBP1) complex is a death signal in a recently
identified type of programmed cell demise, ferroptosis. How the enzymatic
complex selects sn2-ETE-PE as the substrate among 1 of ∼100 total oxidizable
membrane PUFA phospholipids is a central, yet unresolved question.
To unearth the highly selective and specific mechanisms of catalytic
competence, we used a combination of redox lipidomics, mutational
and computational structural analysis to show they stem from (i) reactivity
toward readily accessible hexagonally organized membrane sn2-ETE-PEs, (ii) relative preponderance of sn2-ETE-PE
species vs other sn2-ETE-PLs, and (iii) allosteric
modification of the enzyme in the complex with PEBP1. This emphasizes
the role of enzymatic vs random stochastic free radical reactions
in ferroptotic death signaling
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