262 resultados para MITOCHONDRIAL PERMEABILITY TRANSITION


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Phylogenetic relationships within the Tabanidae are largely unknown, despite their considerable medical and ecological importance. The first robust phylogenetic hypothesis for the horse fly tribe Scionini is provided, completing the systematic placement of all tribes in the subfamily Pangoniinae. The Scionini consists of seven mostly southern hemisphere genera distributed in Australia, New Guinea, New Zealand and South America. A 5757. bp alignment of 6 genes, including mitochondrial (COI and COII), ribosomal (28S) and nuclear (AATS and CAD regions 1, 3 and 4) genes, was analysed for 176 taxa using both Bayesian and maximum likelihood approaches. Results indicate the Scionini are strongly monophyletic, with the exclusion of the only northern hemisphere genus Goniops. The South American genera Fidena, Pityocera and Scione were strongly monophyletic, corresponding to current morphology-based classification schemes. The most widespread genus Scaptia was paraphyletic and formed nine strongly supported monophyletic clades, each corresponding to either the current subgenera or several previously synonymised genera that should be formally resurrected. Molecular results also reveal a newly recognised genus endemic to New Zealand, formerly placed within Scaptia. Divergence time estimation was employed to assess the global biogeographical patterns in the Pangoniinae. These analyses demonstrated that the Scionini are a typical Gondwanan group whose diversification was influenced by the fragmentation of that ancient land mass. Furthermore, results indicate that the Scionini most likely originated in Australia and subsequently radiated to New Zealand and South American by both long distance dispersal and vicariance. The phylogenetic framework of the Scionini provided herein will be valuable for taxonomic revisions of the Tabanidae.

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Migraine is a common neurological disorder characterised by debilitating head pain and an assortment of additional symptoms which can include nausea, emesis, photophobia, phonophobia and occasionally visual sensory disturbances. Migraine is a complex disease caused by an interplay between predisposing genetic variants and environmental factors. It affects approximately 12 % of studied Caucasian populations with affected individuals being predominantly female. Genes involved in neurological, vascular or hormonal pathways have all been implicated in predisposition towards developing migraine. All of these are nuclear encoded genes, but given the role of mitochondria in a number of neurological disorders and in energy production it is possible that mitochondrial variants may play a role in the pathogenesis of this disease. Mitochondrial DNA has been a useful tool for studying population genetics and human genetic diseases due to the clear inheritance shown through successive generations. Given the clear gender bias found in migraine patients it may be important to investigate X-linked inheritance and mitochondrial-related variants in this disorder. This paper explores the possibility that mitochondrial DNA changes may play a role in migraine. Few variants in the mitochondrial genome have so far been investigated in migraine and new studies should be aimed towards investigating the role of mitochondrial DNA in this common disorder.

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The high risk of metabolic disease traits in Polynesians may be partly explained by elevated prevalence of genetic variants involved in energy metabolism. The genetics of Polynesian populations has been shaped by island hoping migration events which have possibly favoured thrifty genes. The aim of this study was to sequence the mitochondrial genome in a group of Maoris in an effort to characterise genome variation in this Polynesian population for use in future disease association studies. We sequenced the complete mitochondrial genomes of 20 non-admixed Maori subjects using Affymetrix technology. DNA diversity analyses showed the Maori group exhibited reduced mitochondrial genome diversity compared to other worldwide populations, which is consistent with historical bottleneck and founder effects. Global phylogenetic analysis positioned these Maori subjects specifically within mitochondrial haplogroup - B4a1a1. Interestingly, we identified several novel variants that collectively form new and unique Maori motifs – B4a1a1c, B4a1a1a3 and B4a1a1a5. Compared to ancestral populations we observed an increased frequency of non-synonymous coding variants of several mitochondrial genes in the Maori group, which may be a result of positive selection and/or genetic drift effects. In conclusion, this study reports the first complete mitochondrial genome sequence data for a Maori population. Overall, these new data reveal novel mitochondrial genome signatures in this Polynesian population and enhance the phylogenetic picture of maternal ancestry in Oceania. The increased frequency of several mitochondrial coding variants makes them good candidates for future studies aimed at assessment of metabolic disease risk in Polynesian populations.

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A growing body of evidence suggests that mitochondrial function may be important in brain development and psychiatric disorders. However, detailed expression profiles of those genes in human brain development and fear-related behavior remain unclear. Using microarray data available from the public domain and the Gene Ontology analysis, we identified the genes and the functional categories associated with chronological age in the prefrontal cortex (PFC) and the caudate nucleus (CN) of psychiatrically normal humans ranging in age from birth to 50 years. Among those, we found that a substantial number of genes in the PFC (115) and the CN (117) are associated with the GO term: mitochondrion (FDR qv <0.05). A greater number of the genes in the PFC (91%) than the genes in the CN (62%) showed a linear increase in expression during postnatal development. Using quantitative PCR, we validated the developmental expression pattern of four genes including monoamine oxidase B (MAOB), NADH dehydrogenase flavoprotein (NDUFV1), mitochondrial uncoupling protein 5 (SLC25A14) and tubulin beta-3 chain (TUBB3). In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in the PFC were comparable to the pattern observed in humans (p<0.05). However, mice selectively bred for high fear did not exhibit normal developmental changes of MAOB and TUBB3. These findings suggest that the genes associated with mitochondrial function in the PFC play a significant role in brain development and fear-related behavior.

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Melanoma is the most aggressive form of skin cancer. Five-year survival rates for patients with metastatic melanoma are less than 10%, with a median survival of 6 to 9 months. Despite a number of clinical trials for metastatic melanoma, the treatment options for patients are limited. Palliation is often the main goal of treatment. This constructivist grounded theory study is seeking to examine how people with metastatic melanoma negotiate the transition to palliative care. The method of sampling is purposive and data have been generated through semi-structured interviews with those with metastatic melanoma and partners. Open, focused and theoretical coding of data from 13 interviews conducted to date has produced analytical concepts that reflect how the transition is negotiated. These concepts depict ways in which individuals interact with a fragmented health care system and how meanings are constructed around the rapid progression of the disease and uncertain treatment decisions. The preliminary findings reported upon here are being further explored with a larger sample. The findings to date highlight the need for improved coordination of services for those living with metastatic melanoma, and improved support for individuals dealing with uncertainty.

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The role of the screen producer is ramifying. Not only are there numerous producer categories, but the screen producer function is also found on a continuum across film, television, advertising, corporate video, and the burgeoning digital media sector. In recent years, fundamental changes to distribution and consumption practices and technologies should have had a correlate impact on screen production practices and on the role of existing screen producers. At the same time, new and recent producers are learning and practicing their craft in a field that has already been transformed by digitisation and media convergence. Our analysis of the work, experience and outlook of screen producers in this chapter is based on data collected in the Australian Screen Producer Survey (ASPS), a nation-wide survey conducted by the ARC Centre of Excellence for Creative Industries and Innovation, the media marketing firm Bergent Research, and the Centre for Screen Business at the Australian Film, Television and Radio School (AFTRS) in 2008/09 and 2011. We analyse the results to better understand the practice of screen production in a period of industry transition, and to recognise the persistence of established production cultures that serve to distinguish different industry sectors.

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Students making the transition from high school to university often encounter many stressors and new experiences. Many students adjust successfully to university; however, some students do not, often resulting in attrition from the university and mental health issues. The primary aim of the current study was to examine the effects that optimism, self-efficacy, depression, and anxiety have on an individual's life stress and adaptation to university. Eighty-four first-year, full-time students from the Queensland University of Technology (60 female, 24 male) who had entered university straight from high school completed the study. Participants completed a questionnaire assessing their levels of optimism, self-efficacy, depression, anxiety, perceived level of life stress and adaptation to university. In line with predictions, results showed that optimism, depression, and anxiety each had a significant relationship with students’ perceived level of stress. Furthermore, self-efficacy and depression had a significant relationship with adaptation to university. We conclude that students with high levels of optimism and low levels of depression and anxiety will adapt better when making the transition from high school to university. In addition, students with high levels of self-efficacy and low levels of depression will experience less life stress in their commencement year of university. The implications of this study are outlined.

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Bcl-x(l) and Bax play important roles in the regulation of apoptosis. This study investigated the involvement of the mitochondrial death pathway and the role of Bcl-x(l) and Bax in the escape from apoptosis after prolonged serum deprivation in Madin-Darby canine kidney (MDCK) cells. Low level apoptosis and basal activity of the mitochondrial death pathway were detectable in normal cell growth. In serum deprivation, mitosis was partially suppressed, and the mitochondrial activity was stimulated. The level of apoptosis continuously rose over 48 h. This rise was concomitant with the increasing presence of cytochrome c in cytosol. However, both apoptosis and cytosolic cytochrome c fell dramatically at 72 h. Elevation of whole cell Bcl-x(l) and redistribution of Bcl-x(l) protein from cytosol to the membrane at 48 h and 72 h was observed. Redistribution of Bax protein from the membrane to cytosol occurred at 24 h, and remained steady to 72 h. Bax/Bcl-x(l) coimmunoprecipitation by anti-Bax antibody showed reduced Bax/Bcl-x(l) interaction at the membrane at 72 h, but not at 24 or 48 h. These results suggest that apoptosis upon serum withdrawal results from the leakage of cytochrome c to cytosol. Amelioration of the leakage of cytochrome c and apoptosis requires not only the increase of Bcl-x(l)/Bax ratio, but also the release of Bcl-x(l) from Bax at the membrane.

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Enormous progress has been made towards understanding the role of specific factors in the process of epithelial-mesenchymal transition (EMT); however, the complex underlying pathways and the transient nature of the transition continues to present significant challenges. Targeting tumour cell plasticity underpinning EMT is an attractive strategy to combat metastasis. Global gene expression profiling and high-content analyses are among the strategies employed to identify novel EMT regulators. In this review, we highlight several approaches to systematically interrogate key pathways involved in EMT, with particular emphasis on the features of multiparametric, high-content imaging screening strategies that lend themselves to the systematic discovery of highly significant modulators of tumour cell plasticity.

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TCNQ·− radical anions (TCNQ = 7,7,8,8,-tetracyanoquinodimethane) form a wide range of semiconducting coordination polymers when coordinated to transition metals. Some such as CuTCNQ and AgTCNQ exhibit molecular switching and memory storage properties; others have intriguing magnetic properties and for example may behave as molecular magnets at low temperature. In this review, the electro- and photo-chemical synthesis and characterization of this important class of material is reviewed. In particular, the electrochemistry and the redox properties of TCNQ derivatives of coordination polymers based on Cu, Ag, Mn, Fe, Co, Ni, Zn and Cd transition metals are surveyed, with an emphasis on the mechanistic aspects of their electrochemical formation via nucleation–growth processes. Given that TCNQ is an extremely good electron acceptor, readily forming TCNQ•− and TCNQ2-, electrochemical reduction of TCNQ in the presence of a transition metal ion provides an ideal method for synthesis of metal-TCNQ materials by electrocrystallization from organic solvents and ionic liquids or solid-solid transformation using TCNQ modified electrodes from aqueous media containing transition metal electrolytes. The significance of the reversible formal potential (E0f) in these studies is discussed. The coupling of electrocrystallisation on electrode surfaces and microscopic characterization of the electrodeposited materials reveals a wide range of morphologies and phases which strongly influence their properties and applications. Since TCNQ also can be photo-reduced in the presence of suitable electron donors, analogous photochemical approaches to the synthesis of TCNQ-transition metal derivatives are available. The advantages of electrochemical and photochemical methods of synthesis relative to chemical synthesis are outlined.

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Teachers in inclusive early education classrooms face competing pressures that are highlighted as children transition from play-based settings into formal school. Their challenge is to engage in pedagogical practice that caters for the complex range of school entrants. Yet the existing literature reports on transition challenges for separate groups of children rather than on shared needs or processes within diverse class populations. This study addressed this gap by investigating practices that supported transition in three Australian sites in which the populations represented different types of pedagogic challenge. Four themes regarding inclusion and transition were identified from a synthesis of the literature and applied to three cases. Results indicated that teachers adopted a range of approaches framed by the visibility of diversity, by classroom and school context and by the teachers’ professional transition in enacting changing policies. The results suggest that competing demands are balanced through dynamic, contextually framed strategies of relevance to both ECEC and schools.

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Estrogen receptor (ER)-β has been shown to possess a tumor suppressive effect, and is a potential target for cancer therapy. Using gene-expression meta-analysis of human malignant pleural mesothelioma, we identified an ESR2 (ERβ coding gene) signature. High ESR2 expression was strongly associated with low succinate dehydrogenase B (SDHB) (which encodes a mitochondrial respiratory chain complex II subunit) expression. We demonstrate that SDHB loss induced ESR2 expression, and that activated ERβ, by over-expression or by selective agonist stimulation, negatively affected oxidative phosphorylation compromising mitochondrial complex II and IV activity. This resulted in reduced mitochondrial ATP production, increased glycolysis dependence and impaired cell proliferation. The observed in vitro effects were phenocopied in vivo using a selective ERβ agonist in a mesothelioma mouse model. On the whole, our data highlight an unforeseen interaction between ERβ-mediated tumor suppression and energy metabolism that may be exploited to improve on the therapy for clinical management of malignant mesothelioma.