Acyl-CoA oxidase is imported as a heteropentameric, cofactor-containing complex into peroxisomes of Yarrowia lipolytica

Five isoforms of acyl-CoA oxidase (Aox), designated Aox1p to Aox5p, constitute a 443-kD heteropentameric complex containing one polypeptide chain of each isoform within the peroxisomal matrix of the yeast Yarrowia lipolytica. Assembly of the Aox complex occurs in the cytosol and precedes its import into peroxisomes. Peroxisomal targeting of the Aox complex is abolished in a mutant lacking the peroxin Pex5p, a component of the matrix protein targeting machinery. Import of the Aox complex into peroxisomes does not involve the cytosolic chaperone Pex20p, which mediates the oligomerization and import of peroxisomal thiolase. Aox2p and Aox3p play a pivotal role in the formation of the Aox complex in the cytosol and can substitute for one another in promoting assembly of the complex. In vitro, these subunits retard disassembly of the Aox complex and increase the efficiency of its reassembly. Neither Aox2p nor Aox3p is required for acquisition of the cofactor FAD by other components of the complex. We provide evidence that the Aox2p- and Aox3p-assisted assembly of the Aox complex in the cytosol is mandatory for its import into peroxisomes and that no component of the complex can penetrate the peroxisomal matrix as a monomer

Patients' internet use in New Zealand for information about medicines: Implications for policy and practice

BACKGROUND: The ubiquitous use of the internet sees patients increasingly look online for information about their medicines. OBJECTIVE: This study aimed to understand the use of internet to meet medicine information needs of a sample of New Zealand patients. METHOD: Using a descriptive exploratory approach 60 mental health and general medical adult patients at one large urban were interviewed. These semi-structured interviews were audio recorded, transcribed and coded for inductive thematic analysis. FINDINGS: This study found that the internet is frequently used to meet the medicines information needs of patients. Despite the ease of access to information on the internet patients need guidance to locate credible and trustworthy online resources. CONCLUSIONS: Implications from this study relate to both practice and policy, and include the need for health professionals to have enhanced communication skills as they become information brokers who provide supplementary, reliable sources of patient-centric medicines information. Having a New Zealand specific website that includes an extensive section on medicines is a policy recommendation of this study, as is identifying tools to readily identify patients’ needs and preferences for medicines information

Fusion of Small Peroxisomal Vesicles in Vitro Reconstructs an Early Step in the in Vivo Multistep Peroxisome Assembly Pathway of Yarrowia lipolytica

We have identified and purified six subforms of peroxisomes, designated P1 to P6, from the yeast, Yarrowia lipolytica. An analysis of trafficking of peroxisomal proteins in vivo suggests the existence of a multistep peroxisome assembly pathway in Y. lipolytica. This pathway operates by conversion of peroxisomal subforms in the direction P1, P2→P3→P4→P5→P6 and involves the import of various peroxisomal proteins into distinct vesicular intermediates. We have also reconstituted in vitro the fusion of the earliest intermediates in the pathway, small peroxisomal vesicles P1 and P2. Their fusion leads to the formation of a larger and more dense peroxisomal vesicle, P3. Fusion of P1 and P2 in vitro requires cytosol and ATP hydrolysis and is inhibited by antibodies to two membrane-associated ATPases of the AAA family, Pex1p and Pex6p. We provide evidence that the fusion in vitro of P1 and P2 peroxisomes reconstructs an actual early step in the peroxisome assembly pathway operating in vivo in Y. lipolytica

Peroxisome division in the yeast Yarrowia lipolytica is regulated by a signal from inside the peroxisome

We describe an unusual mechanism for organelle division. In the yeast Yarrowia lipolytica, only mature peroxisomes contain the complete set of matrix proteins. These mature peroxisomes assemble from several immature peroxisomal vesicles in a multistep pathway. The stepwise import of distinct subsets of matrix proteins into different immature intermediates along the pathway causes the redistribution of a peroxisomal protein, acyl-CoA oxidase (Aox), from the matrix to the membrane. A significant redistribution of Aox occurs only in mature peroxisomes. Inside mature peroxisomes, the membrane-bound pool of Aox interacts with Pex16p, a membrane-associated protein that negatively regulates the division of early intermediates in the pathway. This interaction inhibits the negative action of Pex16p, thereby allowing mature peroxisomes to divide

A Systematic Literature Review on Technology-Enhanced Learning in Medical Education Authors

This systematic review was aimed to evaluate the effectiveness of technology-enhanced learning (TEL) used in medical teaching for undergraduate medical students. The objectives are to (a) identify various teaching modalities which are used to enhance TEL; (b) evaluate whether TEL is more effective than traditional learning (TL) in cognitive and affective learning domain outcome. The empirical studies were searched in the following databases: Google Scholar, MEDLINE, ERIC, ProQuest, Cochrane Library and Scopus. All papers published from 2008 to 2018 were included. From eligible studies, the study design, study field, study population, intervention methods, type of assessment and learning achievement were abstracted and summarized the information. The search results were independently reviewed by two authors. From a pool of 1384 articles, 43 eligible articles were identified, enrolling 7292 undergraduate medical students examining comparative study between TEL and traditional learning. The results showed that there was a high degree of heterogeneity seen amongst the included studies in terms of TEL modalities used. The majority of intervention studies favoured online resources, while the rest used various offline multimedia electronic devices, virtual simulations and blended modes. Overall findings showed promising data that TEL is better than TL with regards to knowledge gain and skill acquisition, as well as providing higher student satisfaction. In all, the findings present blended learning in a positive and promising light in time, particularly where systematic reviews on technology-enhanced learning in the field of the undergraduate medical programme have produced mixed result

Fusion of Small Peroxisomal Vesicles in Vitro Reconstructs an Early Step in the in Vivo Multistep Peroxisome Assembly Pathway of Yarrowia lipolytica

We have identified and purified six subforms of peroxisomes, designated P1 to P6, from the yeast, Yarrowia lipolytica. An analysis of trafficking of peroxisomal proteins in vivo suggests the existence of a multistep peroxisome assembly pathway in Y. lipolytica. This pathway operates by conversion of peroxisomal subforms in the direction P1, P2→P3→P4→P5→P6 and involves the import of various peroxisomal proteins into distinct vesicular intermediates. We have also reconstituted in vitro the fusion of the earliest intermediates in the pathway, small peroxisomal vesicles P1 and P2. Their fusion leads to the formation of a larger and more dense peroxisomal vesicle, P3. Fusion of P1 and P2 in vitro requires cytosol and ATP hydrolysis and is inhibited by antibodies to two membrane-associated ATPases of the AAA family, Pex1p and Pex6p. We provide evidence that the fusion in vitro of P1 and P2 peroxisomes reconstructs an actual early step in the peroxisome assembly pathway operating in vivo in Y. lipolytica

Bayesian Orthogonal Least Squares (BOLS) algorithm for reverse engineering of gene regulatory networks

<p>Abstract</p> <p>Background</p> <p>A reverse engineering of gene regulatory network with large number of genes and limited number of experimental data points is a computationally challenging task. In particular, reverse engineering using linear systems is an underdetermined and ill conditioned problem, i.e. the amount of microarray data is limited and the solution is very sensitive to noise in the data. Therefore, the reverse engineering of gene regulatory networks with large number of genes and limited number of data points requires rigorous optimization algorithm.</p> <p>Results</p> <p>This study presents a novel algorithm for reverse engineering with linear systems. The proposed algorithm is a combination of the orthogonal least squares, second order derivative for network pruning, and Bayesian model comparison. In this study, the entire network is decomposed into a set of small networks that are defined as unit networks. The algorithm provides each unit network with P(D|H_i), which is used as confidence level. The unit network with higher P(D|H_i) has a higher confidence such that the unit network is correctly elucidated. Thus, the proposed algorithm is able to locate true positive interactions using P(D|H_i), which is a unique property of the proposed algorithm.</p> <p>The algorithm is evaluated with synthetic and <it>Saccharomyces cerevisiae </it>expression data using the dynamic Bayesian network. With synthetic data, it is shown that the performance of the algorithm depends on the number of genes, noise level, and the number of data points. With Yeast expression data, it is shown that there is remarkable number of known physical or genetic events among all interactions elucidated by the proposed algorithm.</p> <p>The performance of the algorithm is compared with Sparse Bayesian Learning algorithm using both synthetic and <it>Saccharomyces cerevisiae </it>expression data sets. The comparison experiments show that the algorithm produces sparser solutions with less false positives than Sparse Bayesian Learning algorithm.</p> <p>Conclusion</p> <p>From our evaluation experiments, we draw the conclusion as follows: 1) Simulation results show that the algorithm can be used to elucidate gene regulatory networks using limited number of experimental data points. 2) Simulation results also show that the algorithm is able to handle the problem with noisy data. 3) The experiment with Yeast expression data shows that the proposed algorithm reliably elucidates known physical or genetic events. 4) The comparison experiments show that the algorithm more efficiently performs than Sparse Bayesian Learning algorithm with noisy and limited number of data.</p

Sentence processing in anterior superior temporal cortex shows a social-emotional bias

The anterior region of the left superior temporal gyrus/superior temporal sulcus (aSTG/STS) has been implicated in two very different cognitive functions: sentence processing and social-emotional processing. However, the vast majority of the sentence stimuli in previous reports have been of a social or social-emotional nature suggesting that sentence processing may be confounded with semantic content. To evaluate this possibility we had subjects read word lists that differed in phrase/constituent size (single words, 3-word phrases, 6-word sentences) and semantic content (social-emotional, social, and inanimate objects) while scanned in a 7T environment. This allowed us to investigate if the aSTG/STS responded to increasing constituent structure (with increased activity as a function of constituent size) with or without regard to a specific domain of concepts, i.e., social and/or social-emotional content. Activity in the left aSTG/STS was found to increase with constituent size. This region was also modulated by content, however, such that social-emotional concepts were preferred over social and object stimuli. Reading also induced content type effects in domain-specific semantic regions. Those preferring social-emotional content included aSTG/STS, inferior frontal gyrus, posterior STS, lateral fusiform, ventromedial prefrontal cortex, and amygdala, regions included in the "social brain", while those preferring object content included parahippocampal gyrus, retrosplenial cortex, and caudate, regions involved in object processing. These results suggest that semantic content affects higher-level linguistic processing and should be taken into account in future studies