Shedding of host autophagic proteins from the parasitophorous vacuolar membrane of Plasmodium berghei

The hepatic stage of the malaria parasite Plasmodium is accompanied by an autophagy-mediated host response directly targeting the parasitophorous vacuolar membrane (PVM) harbouring the parasite. Removal of the PVM-associated autophagic proteins such as ubiquitin, p62, and LC3 correlates with parasite survival. Yet, it is unclear how Plasmodium avoids the deleterious effects of selective autophagy. Here we show that parasites trap host autophagic factors in the tubovesicular network (TVN), an expansion of the PVM into the host cytoplasm. In proliferating parasites, PVM-associated LC3 becomes immediately redirected into the TVN, where it accumulates distally from the parasite's replicative centre. Finally, the host factors are shed as vesicles into the host cytoplasm. This strategy may enable the parasite to balance the benefits of the enhanced host catabolic activity with the risk of being eliminated by the cell's cytosolic immune defence

Distributed computing methodology for training neural networks in an image-guided diagnostic application

Distributed computing is a process through which a set of computers connected by a network is used collectively to solve a single problem. In this paper, we propose a distributed computing methodology for training neural networks for the detection of lesions in colonoscopy. Our approach is based on partitioning the training set across multiple processors using a parallel virtual machine. In this way, interconnected computers of varied architectures can be used for the distributed evaluation of the error function and gradient values, and, thus, training neural networks utilizing various learning methods. The proposed methodology has large granularity and low synchronization, and has been implemented and tested. Our results indicate that the parallel virtual machine implementation of the training algorithms developed leads to considerable speedup, especially when large network architectures and training sets are used

Components and Interfaces of a Process Management System for Parallel Programs

Parallel jobs are different from sequential jobs and require a different type of process management. We present here a process management system for parallel programs such as those written using MPI. A primary goal of the system, which we call MPD (for multipurpose daemon), is to be scalable. By this we mean that startup of interactive parallel jobs comprising thousands of processes is quick, that signals can be quickly delivered to processes, and that stdin, stdout, and stderr are managed intuitively. Our primary target is parallel machines made up of clusters of SMPs, but the system is also useful in more tightly integrated environments. We describe how MPD enables much faster startup and better runtime management of parallel jobs. We show how close control of stdio can support the easy implementation of a number of convenient system utilities, even a parallel debugger. We describe a simple but general interface that can be used to separate any process manager from a parallel library, which we use to keep MPD separate from MPICH.Comment: 12 pages, Workshop on Clusters and Computational Grids for Scientific Computing, Sept. 24-27, 2000, Le Chateau de Faverges de la Tour, Franc

Strategies for maximizing ATP supply in the microsporidian Encephalitozoon cuniculi: direct binding of mitochondria to the parasitophorous vacuole and clustering of the mitochondrial porin VDAC

Microsporidia are obligate intracellular parasites with extremely reduced genomes and a dependence on host-derived ATP. The microsporidium Encephalitozoon cuniculi proliferates within a membranous vacuole and we investigated how the ATP supply is optimized at the vacuole–host interface. Using spatial EM quantification (stereology), we found a single layer of mitochondria coating substantial proportions of the parasitophorous vacuole. Mitochondrial binding occurred preferentially over the vegetative ‘meront’ stages of the parasite, which bulged into the cytoplasm, thereby increasing the membrane surface available for mitochondrial interaction. In a broken cell system mitochondrial binding was maintained and was typified by electron dense structures (<10 nm long) bridging between outer mitochondrial and vacuole membranes. In broken cells mitochondrial binding was sensitive to a range of protease treatments. The function of directly bound mitochondria, as measured by the membrane potential sensitive dye JC-1, was indistinguishable from other mitochondria in the cell although there was a generalized depression of the membrane potential in infected cells. Finally, quantitative immuno-EM revealed that the ATP-delivering mitochondrial porin, VDAC, was concentrated atthe mitochondria-vacuole interaction site. Thus E. cuniculi appears to maximize ATP supply by direct binding of mitochondria to the parasitophorous vacuole bringing this organelle within 0.020 microns of the growing vegetative form of the parasite. ATP-delivery is further enhanced by clustering of ATP transporting porins in those regions of the outer mitochondrial membrane lying closest to the parasite

Reconstruction of primordial density fields

The Monge-Ampere-Kantorovich (MAK) reconstruction is tested against cosmological N-body simulations. Using only the present mass distribution sampled with particles, and the assumption of homogeneity of the primordial distribution, MAK recovers for each particle the non-linear displacement field between its present position and its Lagrangian position on a primordial uniform grid. To test the method, we examine a standard LCDM N-body simulation with Gaussian initial conditions and 6 models with non-Gaussian initial conditions: a chi-squared model, a model with primordial voids and four weakly non-Gaussian models. Our extensive analyses of the Gaussian simulation show that the level of accuracy of the reconstruction of the nonlinear displacement field achieved by MAK is unprecedented, at scales as small as about 3 Mpc. In particular, it captures in a nontrivial way the nonlinear contribution from gravitational instability, well beyond the Zel'dovich approximation. This is also confirmed by our analyses of the non-Gaussian samples. Applying the spherical collapse model to the probability distribution function of the divergence of the displacement field, we also show that from a well-reconstructed displacement field, such as that given by MAK, it is possible to accurately disentangle dynamical contributions induced by gravitational clustering from possible initial non-Gaussianities, allowing one to efficiently test the non-Gaussian nature of the primordial fluctuations. In addition, a simple application of MAK using the Zel'dovich approximation allows one to also recover accurately the present-day peculiar velocity field on scales of about 8 Mpc.Comment: Version to appear in MNRAS, 24 pages, 21 figures appearing (uses 35 figure files), 1 tabl

Merozoite release from Plasmodium falciparum-infected erythrocytes involves the transfer of DiIC16 from infected cell membrane to Maurer’s clefts

Merozoite release from infected erythrocytes is a complex process, which is still not fully understood. Such process was characterised at ultra-structural level in this work by labelling erythrocyte membrane with a fluorescent lipid probe and subsequent photo-conversion into an electron-dense precipitate. A lipophilic DiIC16 probe was inserted into the infected erythrocyte surface and the transport of this phospholipid analogue through the erythrocyte membrane was followed up during 48 h of the asexual erythrocyte cycle. The lipid probe was transferred from infected erythrocyte membranes to Maurer’s clefts during merozoite release, thereby indicating that these membranes remained inside host cells after parasite release. Fluorescent structures were never observed inside infected erythrocytes preceding merozoite exit and merozoites released from infected erythrocyte were not fluorescent. However, specific precipitated material was localised bordering the parasitophorous vacuole membrane and tubovesicular membranes when labelled non-infected erythrocytes were invaded by merozoites. It was revealed that lipids were interchangeable from one membrane to another, passing from infected erythrocyte membrane to Maurer’s clefts inside the erythrocyte ghost, even after merozoite release. Maurer’s clefts became photo-converted following merozoite release, suggesting that these structures were in close contact with infected erythrocyte membrane during merozoite exit and possibly played some role in malarial parasite exit from the host cell

Workstation Clusters for Parallel Computing

Workstation clusters have become an increasingly popular alternative to traditional parallel supercomputers for many workloads requiring high performance computing. The use of parallel computing for scientific simulations has increased tremendously in the last ten years, and parallel implementations of scientific simulation codes are now in widespread use. There are two dominant parallel hardware/software architectures in use today: distributed memory, and shared memory. Systems implementing shared memory provide cooperating processes with a shared memory address space that can be accessed by all processors. In shared memory systems, parallel processing occurs through the use of shared data structures, or through emulation of message passing semantics in software. Distributed memory systems are composed of a number of interconnected computational nodes, which do not share memory, but can communicate with each other through a high-performance network of some kind. Parallelism is achieved on distributed memory systems with multiple copies of the parallel program running on different nodes, sending messages to each other to coordinate computations. The messages used in a distributed memory parallel program typically contain application data, synchronization information, and other data that controls the execution of the parallel program