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Find video protocols related to scientific articles indexed in Pubmed.
Deficiency of the exportomer components Pex1, Pex6, and Pex15 causes enhanced pexophagy in Saccharomyces cerevisiae.
Autophagy
PUBLISHED: 03-18-2014
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Turnover of damaged, dysfunctional, or excess organelles is critical to cellular homeostasis. We screened mutants disturbed in peroxisomal protein import, and found that a deficiency in the exportomer subunits Pex1, Pex6, and Pex15 results in enhanced turnover of peroxisomal membrane structures compared with other mutants. Strikingly, almost all peroxisomal membranes were associated with phagophore assembly sites in pex1? atg1? cells. Degradation depended on Atg11 and the pexophagy receptor Atg36, which mediates degradation of superfluous peroxisomes. Mutants of PEX1, PEX6, and PEX15 accumulate ubiquitinated receptors at the peroxisomal membrane. This accumulation has been suggested to trigger pexophagy in mammalian cells. We show by genetic analysis that preventing this accumulation does not abolish pexophagy in Saccharomyces cerevisiae. We find Atg36 is modified in pex1? cells even when Atg11 binding is prevented, suggesting Atg36 modification is an early event in the degradation of dysfunctional peroxisomal structures in pex1? cells via pexophagy.
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Effects of rifampin-based antituberculosis therapy on plasma efavirenz concentrations in children vary by CYP2B6 genotype.
AIDS
PUBLISHED: 11-02-2013
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An efavirenz-based antiretroviral therapy (ART) regimen is preferred for children more than 3 years of age with tuberculosis. However, rifampin, a key component of antituberculosis therapy, induces CYP2B6. An increased dose of efavirenz is recommended in adults weighing more than 50 kg who require rifampin, but there is scant information in children being treated for tuberculosis.
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What are the levels of evidence on which we base decisions for surgical management of lower extremity bone tumors?
Clin. Orthop. Relat. Res.
PUBLISHED: 06-22-2013
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Benign and malignant lower extremity primary bone tumors are among the least common conditions treated by orthopaedic surgeons. The literature supporting their surgical management has historically been in the form of observational studies rather than prospective controlled studies. Observational studies are prone to confounding bias, sampling bias, and recall bias.
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Epidemiology of Staphylococcus aureus bacteraemia at a tertiary childrens hospital in Cape Town, South Africa.
PLoS ONE
PUBLISHED: 01-01-2013
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Staphylococcus aureus is an important pathogen in paediatric patients with bloodstream infections. The epidemiology of S. aureus bacteraemia, however, has not been well documented in children in South Africa.
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It is time to consider third-line options in antiretroviral-experienced paediatric patients?
J Int AIDS Soc
PUBLISHED: 05-30-2011
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The historic use of full-dose ritonavir as part of an unboosted protease inhibitor (PI)-based antiretroviral therapy regimen in some South African children contributes to the frequent accumulation of major PI resistance mutations.
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Lopinavir exposure is insufficient in children given double doses of lopinavir/ritonavir during rifampicin-based treatment for tuberculosis.
Antivir. Ther. (Lond.)
PUBLISHED: 05-11-2011
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Coadministration of rifampicin dramatically reduces the concentrations of protease inhibitors. A pharmacokinetic study in healthy adults showed that doubling the dose of coformulated lopinavir/ritonavir was able to overcome the inducing effect of rifampicin. We evaluated this strategy in children treated with rifampicin-based antituberculosis therapy attending antiretroviral clinics in South Africa.
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Peroxisome biogenesis: recent advances.
Curr. Opin. Cell Biol.
PUBLISHED: 03-07-2011
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In recent years, it has become evident that peroxisomes form part of the endomembrane system. Peroxisomes can form from the ER via a maturation process and they can multiply by growth and division, whereby the ER provides membrane for growth and ongoing fission (Figure 1). Until very recently, it was widely accepted that most peroxisomal membrane proteins (PMPs) insert directly into peroxisomes, whereas a small subset of PMPs traffic via the ER. In this minireview, we focus mainly on PMP biogenesis, and highlight recent advances in peroxisomal matrix protein import, fission and segregation in yeast.
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BCG Vaccination in HIV-Infected Children.
Tuberc Res Treat
PUBLISHED: 02-02-2011
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Despite the use of Bacillus Calmette-Guérin (BCG) vaccination for many years, infants and young children exposed to adults with infectious forms of tuberculosis (TB) are at high risk of developing complicated TB disease. This risk is much higher among HIV-infected children, and data on BCG protective efficacy in HIV-infected children is lacking. Recent research on BCG safety in HIV-infected infants has resulted in policy shifts, but implementation is challenging. New approaches to preventing TB among infants and children, particularly HIV-infected infants, are needed. This paper briefly reviews BCG safety and efficacy considerations in HIV-infected infants and discusses other approaches to preventing TB, including new TB vaccines and vaccination strategies.
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Sequencing of antiretroviral therapy in children in low- and middle-income countries.
Curr Opin HIV AIDS
PUBLISHED: 01-05-2010
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With recent changes in global pediatric HIV policy to initiate treatment immediately after early infant diagnosis, there will be greater demand for feasible antiretroviral sequencing strategies that will support children through adulthood. This review will discuss HIV treatment (antiretroviral therapy) failure, regimen switching, and sequencing approaches in children.
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A dual function for Pex3p in peroxisome formation and inheritance.
J. Cell Biol.
PUBLISHED: 11-09-2009
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Saccharomyces cerevisiae Pex3p has been shown to act at the ER during de novo peroxisome formation. However, its steady state is at the peroxisomal membrane, where its role is debated. Here we show that Pex3p has a dual function: one in peroxisome formation and one in peroxisome segregation. We show that the peroxisome retention factor Inp1p interacts physically with Pex3p in vitro and in vivo, and split-GFP analysis shows that the site of interaction is the peroxisomal membrane. Furthermore, we have generated PEX3 alleles that support peroxisome formation but fail to support recruitment of Inp1p to peroxisomes, and as a consequence are affected in peroxisome segregation. We conclude that Pex3p functions as an anchor for Inp1p at the peroxisomal membrane, and that this function is independent of its role at the ER in peroxisome biogenesis.
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Low rates of hepatotoxicity in HIV-infected children on anti-retroviral therapy with and without isoniazid prophylaxis.
J. Trop. Pediatr.
PUBLISHED: 08-26-2009
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This study investigates the incidence of hepatotoxicity in HIV-infected children during anti-retroviral therapy (ART) and the impact of concomitant use of isoniazid preventive therapy. It is a retrospective cohort analysis of HIV-infected children who commenced ART or were followed up between September 1998 and November 2005. Alanine transferase levels were measured at baseline, at 1, 3 and 6 months and then 6 monthly thereafter. Of the 598 children included in the study, 425 were taking ART alone, 73 ART and isoniazid, 39 isoniazid alone and 61 neither isoniazid nor ART. There was no increased risk of hepatotoxicity with ART with or without isoniazid compared to the control group over a 2-year period. Grade 3 or 4 ALT elevations occurred in 19 (3.4%) children, with no cases of fulminant hepatic failure. Severe hepatic events are uncommon in children on ART or isoniazid. There is no increased risk of hepatotoxicity with ART and concurrent isoniazid preventive therapy.
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The Hsp90/Cdc37p chaperone system is a determinant of molybdate resistance in Saccharomyces cerevisiae.
Yeast
PUBLISHED: 04-29-2009
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Saccharomyces cerevisiae lacks enzymes that contain the molybdopterin co-factor and therefore any requirement for molybdenum as a trace mineral supplement. Instead, high molybdate levels are inhibitory to its growth. Low cellular levels of heat shock protein 90 (Hsp90), an essential chaperone, were found to enhance this sensitivity to molybdate. Certain Hsp90 point mutations and co-chaperone protein defects that partially compromise the function of the Hsp90/Cdc37p chaperone system also rendered S. cerevisiae hypersensitive to high molybdate levels. Sensitivity was especially apparent with mutations close to the Hsp90 nucleotide binding site, with the loss of the non-essential co-chaperone Sti1p (the equivalent of mammalian Hop), and with the abolition of residue Ser14 phosphorylation on the essential co-chaperone Cdc37p. While it remains to be proved that these effects reflect direct inhibition of the Hsp90 of the cell by the MoO(4) (2+) oxyanion in vivo; this possibility is suggested by molybdate sensitivity arising with a mutation in the Hsp90 nucleotide binding site that does not generate stress sensitivity or an impaired stress response. Molybdate sensitivity may therefore be a useful phenotype to score when studying mutations in this chaperone system.
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Structural basis of the radicicol resistance displayed by a fungal hsp90.
ACS Chem. Biol.
PUBLISHED: 02-25-2009
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Heat shock protein 90 (Hsp90) is a promising cancer drug target, as multiple oncogenic proteins are destabilized simultaneously when it loses its activity in tumor cells. Highly selective Hsp90 inhibitors, including the natural antibiotics geldanamycin (GdA) and radicicol (RAD), inactivate this essential molecular chaperone by occupying its nucleotide binding site. Often cancer drug therapy is compromised by the development of resistance, but a resistance to these Hsp90 inhibitors should not arise readily by mutation of those amino acids within Hsp90 that facilitate inhibitor binding, as these are required for the essential ATP binding/ATPase steps of the chaperone cycle and are tightly conserved. Despite this, the Hsp90 of a RAD-producing fungus is shown to possess an unusually low binding affinity for RAD but not GdA. Within its nucleotide binding site a normally conserved leucine is replaced by isoleucine, though the chaperone ATPase activity is not severely affected. Inserted into the Hsp90 of yeast, this conservative leucine to isoleucine substitution recreated this lowered affinity for RAD in vitro. It also generated a substantially enhanced resistance to RAD in vivo. Co-crystal structures reveal that the change to isoleucine is associated with a localized increase in the hydration of an Hsp90-bound RAD but not GdA. To the best of our knowledge, this is the first demonstration that it is possible for Hsp90 inhibitor resistance to arise by subtle alteration to the structure of Hsp90 itself.
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Effect of rifampicin on efavirenz pharmacokinetics in HIV-infected children with tuberculosis.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 02-19-2009
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Rifampicin may reduce plasma efavirenz concentrations by inducing the expression of the cytochrome P450 2B6, which metabolizes efavirenz. However, there is no data in pediatric patient populations.
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South African measles outbreak 2009 - 2010 as experienced by a paediatric hospital.
S. Afr. Med. J.
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Between 2009 and 2010, South Africa experienced a major measles outbreak, with more than 18 000 confirmed cases reported to the National Institute of Communicable Diseases.
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Systemic amyloidosis complicating multidrug-resistant tuberculosis in childhood.
Pediatr. Infect. Dis. J.
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Multidrug-resistant tuberculosis is increasingly common and is associated with long diagnostic delay and high morbidity. We present a 7-year-old child who developed steroid-resistant nephrotic syndrome while receiving treatment for tuberculosis. Renal biopsy results showed systemic amyloidosis; culture of peritoneal tissue confirmed disseminated multidrug-resistant tuberculosis.
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Atg36: the Saccharomyces cerevisiae receptor for pexophagy.
Autophagy
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Eukaryotic cells adapt their organelle composition and abundance according to environmental conditions. Analysis of the peroxisomal membrane protein Pex3 has revealed that this protein plays a crucial role in peroxisome maintenance as it is required for peroxisome formation, segregation and breakdown. Although its function in peroxisome formation and segregation was known to involve its recruitment to the peroxisomal membrane of factors specific for these processes, the role of Pex3 in peroxisome breakdown was unclear until our recent identification of Atg36 as a novel Saccharomyces cerevisiae Pex3-interacting protein. Atg36 is recruited to peroxisomes by Pex3 and is required specifically for pexophagy. Atg36 is distinct from Atg30, the pexophagy receptor identified in Pichia pastoris. Atg36 interacts with Atg11 in vivo, and to a lesser extent with Atg8. These latter proteins link autophagic cargo receptors to the core autophagy machinery. Like other autophagic cargo receptors, Atg36 is a suicide receptor and is broken down in the vacuole together with its cargo. Unlike other cargo receptors, the interaction between Atg36 and Atg8 does not seem to be direct. Our recent findings suggest that Atg36 is a novel pexophagy receptor that may target peroxisomes for degradation via a noncanonical mechanism.
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Farnesyl diphosphate synthase, the target for nitrogen-containing bisphosphonate drugs, is a peroxisomal enzyme in the model system Dictyostelium discoideum.
Biochem. J.
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NBP (nitrogen-containing bisphosphonate) drugs protect against excessive osteoclast-mediated bone resorption. After binding to bone mineral, they are taken up selectively by the osteoclasts and inhibit the essential enzyme FDPS (farnesyl diphosphate synthase). NBPs inhibit also growth of amoebae of Dictyostelium discoideum in which their target is again FDPS. A fusion protein between FDPS and GFP (green fluorescent protein) was found, in D. discoideum, to localize to peroxisomes and to confer resistance to the NBP alendronate. GFP was also directed to peroxisomes by a fragment of FDPS comprising amino acids 1-22. This contains a sequence of nine amino acids that closely resembles the nonapeptide PTS2 (peroxisomal targeting signal type 2): there is only a single amino acid mismatch between the two sequences. Mutation analysis confirmed that the atypical PTS2 directs FDPS into peroxisomes. Furthermore, expression of the D. discoideum FDPS-GFP fusion protein in strains of Saccharomyces cerevisiae defective in peroxisomal protein import demonstrated that import of FDPS into peroxisomes was blocked in a strain lacking the PTS2-dependent import pathway. The peroxisomal location of FDPS in D. discoideum indicates that NBPs have to cross the peroxisomal membrane before they can bind to their target.
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Pex3-anchored Atg36 tags peroxisomes for degradation in Saccharomyces cerevisiae.
EMBO J.
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Peroxisomes undergo rapid, selective autophagic degradation (pexophagy) when the metabolic pathways they contain are no longer required for cellular metabolism. Pex3 is central to the formation of peroxisomes and their segregation because it recruits factors specific for these functions. Here, we describe a novel Saccharomyces cerevisiae protein that interacts with Pex3 at the peroxisomal membrane. We name this protein Atg36 as its absence blocks pexophagy, and its overexpression induces pexophagy. We have isolated pex3 alleles blocked specifically in pexophagy that cannot recruit Atg36 to peroxisomes. Atg36 is recruited to mitochondria if Pex3 is redirected there, where it restores mitophagy in cells lacking the mitophagy receptor Atg32. Furthermore, Atg36 binds Atg8 and the adaptor Atg11 that links receptors for selective types of autophagy to the core autophagy machinery. Atg36 delivers peroxisomes to the preautophagosomal structure before being internalised into the vacuole with peroxisomes. We conclude that Pex3 recruits the pexophagy receptor Atg36. This reinforces the pivotal role played by Pex3 in coordinating the size of the peroxisome pool, and establishes its role in pexophagy in S. cerevisiae.
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Steady-State Pharmacokinetics of Nevirapine Extended-Release Tablets in HIV-1 Infected Children and Adolescents: An Open-Label, Multiple Dose, Cross-Over Study.
Pediatr. Infect. Dis. J.
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To compare steady-state (ss) pharmacokinetic (PK) targets of nevirapine extended-release (NVP-XR) tablets once-daily (QD) with immediate-release (NVP-IR) tablet or oral suspension twice-daily (BID) in HIV-1 infected children and adolescents.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.