41 research outputs found

    Mitophagy plays a central role in mitochondrial ageing

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    The mechanisms underlying ageing have been discussed for decades, and advances in molecular and cell biology of the last three decades have accelerated research in this area. Over this period, it has become clear that mitochondrial function, which plays a major role in many cellular pathways from ATP production to nuclear gene expression and epigenetics alterations, declines with age. The emerging concepts suggest novel mechanisms, involving mtDNA quality, mitochondrial dynamics or mitochondrial quality control. In this review, we discuss the impact of mitochondria in the ageing process, the role of mitochondria in reactive oxygen species production, in nuclear gene expression, the accumulation of mtDNA damage and the importance of mitochondrial dynamics and recycling. Declining mitophagy (mitochondrial quality control) may be an important component of human ageing

    The Utility of Ultrasound for Diagnosing Purulent Infections of the Upper Extremity

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    BACKGROUND: The purpose of this study was to determine the test characteristics of formal ultrasound when used to diagnose upper extremity soft tissue abscess in the setting of suspected infection. METHODS: We completed a retrospective chart review of all patients who had formal ultrasounds at our institution for the indication of diagnosing upper extremity abscess between July 2010 and July 2013. Using presence of purulence as the gold standard for diagnosis of abscess, we calculated the test characteristics of ultrasound. We then performed a series of logistic regression models with ultrasound being the independent variable of interest. RESULTS: Using search criteria consistent with upper extremity abscess, we identified 512 patients who underwent ultrasound examinations during our study period. Of these, 178 met the enrollment criteria. Ultrasound reports revealed 110 negative findings, 37 definitively positive findings, and 31 ambiguous findings. Forty-four patients had a final diagnosis of abscess, and 15 of these patients had negative or ambiguous ultrasounds. The sensitivity of definitively positive ultrasound was 65.9 %. The specificity was 94.0 %. Positive predictive value (PPV) of a definitively positive ultrasound result was 78.4 %, and negative predictive value (NPV) of a definitively negative result was 90 %. Logistic regression demonstrated a statistically significant association between definitively positive ultrasound and abscess, but no association between ambiguous ultrasound and abscess after adjustment for significant covariates. CONCLUSIONS: Ultrasound is not a sensitive method to detect the presence of abscess in the setting of upper extremity infection. However, in this population of patients with suspected abscess, the negative predictive value was high with and without the inclusion of ambiguous results, suggesting reasonable utility of ultrasound as a rule-out test. LEVEL OF EVIDENCE: Diagnostic study, Level I

    Plasmodium falciparum Merozoite Associated Armadillo Protein (PfMAAP) is apically localized in free merozoites and antibodies are associated with reduced risk of malaria

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    Understanding the functional role of proteins expressed by Plasmodium falciparum is an important step toward unlocking potential targets for the development of therapeutic or diagnostic interventions. The armadillo (ARM) repeat protein superfamily is associated with varied functions across the eukaryotes. Therefore, it is important to understand the role of members of this protein family in Plasmodium biology. The Plasmodium falciparum armadillo repeats only (PfARO; Pf3D7_0414900) and P. falciparum merozoite organizing proteins (PfMOP; Pf3D7_0917000) are armadillo-repeat containing proteins previously characterized in P. falciparum. Here, we describe the characterization of another ARM repeat-containing protein in P. falciparum, which we have named the P. falciparum Merozoites-Associated Armadillo repeats protein (PfMAAP). Antibodies raised to three different synthetic peptides of PfMAAP show apical staining of free merozoites and those within the mature infected schizont. We also demonstrate that the antibodies raised to the PfMAAP peptides inhibited invasion of erythrocytes by merozoites from different parasite isolates. In addition, naturally acquired human antibodies to the N- and C- termini of PfMAAP are associated with a reduced risk of malaria in a prospective cohort analysis

    Analysis of Plasmodium falciparum Rh2b deletion polymorphism across different transmission areas

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    Despite significant progress in controlling malaria, the disease remains a global health burden. The intricate interactions the parasite Plasmodium falciparum has with its host allows it to grow and multiply in human erythrocytes. The mechanism by which P. falciparum merozoites invade human erythrocytes is complex, involving merozoite proteins as well as erythrocyte surface proteins. Members of the P. falciparum reticulocyte binding-like protein homolog (PfRh) family of proteins play a pivotal role in merozoite invasion and hence are important targets of immune responses. Domains within the PfRh2b protein have been implicated in its ability to stimulate natural protective antibodies in patients. More specifically, a 0.58 kbp deletion, at the C-terminus has been reported in high frequencies in Senegalese and Southeast Asian parasite populations, suggesting a possible role in immune evasion. We analysed 1218 P. falciparum clinical isolates, and the results show that this deletion is present in Ghanaian parasite populations (48.5% of all isolates), with Kintampo (hyper-endemic, 53.2%), followed by Accra (Hypo-endemic, 50.3%), Cape Coast (meso-endemic, 47.9%) and Sogakope (meso-endemic, 43.15%). Further analysis of parasite genomes stored in the MalariaGEN database revealed that the deletion variant was common across transmission areas globally, with an overall frequency of about 27.1%. Interestingly, some parasite isolates possessed mixed PfRh2b deletion and full-length alleles. We further showed that levels of antibodies to the domain of PfRh2 protein were similar to antibody levels of PfRh5, indicating it is less recognized by the immune system
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