Trafficking of plasmepsin II to the food vacuole of the malaria parasite Plasmodium falciparum

fA amily of aspartic proteases, the plasmepsins (PMs), plays a key role in the degradation of hemoglobin in the Plasmodium falciparum food vacuole. To study the trafficking of proPM II, we have modified the chromosomal PM II gene in P. falciparum to encode a proPM II–GFP chimera. By taking advantage of green fluorescent protein fluorescence in live parasites, the ultrastructural resolution of immunoelectron microscopy, and inhibitors of trafficking and PM maturation, we have investigated the biosynthetic path leading to mature PM II in the food vacuole. Our data support a model whereby proPM II is transported through the secretory system to cytostomal vacuoles and then is carried along with its substrate hemoglobin to the food vacuole where it is proteolytically processed to mature PM II

Progression Analysis and Stage Discovery in Continuous Physiological Processes Using Image Computing

We propose an image computing-based method for quantitative analysis of continuous physiological processes that can be sensed by medical imaging and demonstrate its application to the analysis of morphological alterations of the bone structure, which correlate with the progression of osteoarthritis (OA). The purpose of the analysis is to quantitatively estimate OA progression in a fashion that can assist in understanding the pathophysiology of the disease. Ultimately, the texture analysis will be able to provide an alternative OA scoring method, which can potentially reflect the progression of the disease in a more direct fashion compared to the existing clinically utilized classification schemes based on radiology. This method can be useful not just for studying the nature of OA, but also for developing and testing the effect of drugs and treatments. While in this paper we demonstrate the application of the method to osteoarthritis, its generality makes it suitable for the analysis of other progressive clinical conditions that can be diagnosed and prognosed by using medical imaging

CENP-V is required for centromere organization, chromosome alignment and cytokinesis

The mechanism of mitotic chromosome condensation is poorly understood, but even less is known about the mechanism of formation of the primary constriction, or centromere. A proteomic analysis of mitotic chromosome scaffolds led to the identification of CENP-V, a novel kinetochore protein related to a bacterial enzyme that detoxifies formaldehyde, a by-product of histone demethylation in eukaryotic cells. Overexpression of CENP-V leads to hypercondensation of pericentromeric heterochromatin, a phenotype that is abolished by mutations in the putative catalytic site. CENP-V depletion in HeLa cells leads to abnormal expansion of the primary constriction of mitotic chromosomes, mislocalization and destabilization of the chromosomal passenger complex (CPC) and alterations in the distribution of H3K9me3 in interphase nucleoplasm. CENP-V-depleted cells suffer defects in chromosome alignment in metaphase, lagging chromosomes in anaphase, failure of cytokinesis and rapid cell death. CENP-V provides a novel link between centromeric chromatin, the primary constriction and the CPC

Adaptable data management for systems biology investigations

<p>Abstract</p> <p>Background</p> <p>Within research each experiment is different, the focus changes and the data is generated from a continually evolving barrage of technologies. There is a continual introduction of new techniques whose usage ranges from in-house protocols through to high-throughput instrumentation. To support these requirements data management systems are needed that can be rapidly built and readily adapted for new usage.</p> <p>Results</p> <p>The adaptable data management system discussed is designed to support the seamless mining and analysis of biological experiment data that is commonly used in systems biology (e.g. ChIP-chip, gene expression, proteomics, imaging, flow cytometry). We use different content graphs to represent different views upon the data. These views are designed for different roles: equipment specific views are used to gather instrumentation information; data processing oriented views are provided to enable the rapid development of analysis applications; and research project specific views are used to organize information for individual research experiments. This management system allows for both the rapid introduction of new types of information and the evolution of the knowledge it represents.</p> <p>Conclusion</p> <p>Data management is an important aspect of any research enterprise. It is the foundation on which most applications are built, and must be easily extended to serve new functionality for new scientific areas. We have found that adopting a three-tier architecture for data management, built around distributed standardized content repositories, allows us to rapidly develop new applications to support a diverse user community.</p

Systems biology driven software design for the research enterprise

<p>Abstract</p> <p>Background</p> <p>In systems biology, and many other areas of research, there is a need for the interoperability of tools and data sources that were not originally designed to be integrated. Due to the interdisciplinary nature of systems biology, and its association with high throughput experimental platforms, there is an additional need to continually integrate new technologies. As scientists work in isolated groups, integration with other groups is rarely a consideration when building the required software tools.</p> <p>Results</p> <p>We illustrate an approach, through the discussion of a purpose built software architecture, which allows disparate groups to reuse tools and access data sources in a common manner. The architecture allows for: the rapid development of distributed applications; interoperability, so it can be used by a wide variety of developers and computational biologists; development using standard tools, so that it is easy to maintain and does not require a large development effort; extensibility, so that new technologies and data types can be incorporated; and non intrusive development, insofar as researchers need not to adhere to a pre-existing object model.</p> <p>Conclusion</p> <p>By using a relatively simple integration strategy, based upon a common identity system and dynamically discovered interoperable services, a light-weight software architecture can become the focal point through which scientists can both get access to and analyse the plethora of experimentally derived data.</p

Wndchrm – an open source utility for biological image analysis

<p>Abstract</p> <p>Background</p> <p>Biological imaging is an emerging field, covering a wide range of applications in biological and clinical research. However, while machinery for automated experimenting and data acquisition has been developing rapidly in the past years, automated image analysis often introduces a bottleneck in high content screening.</p> <p>Methods</p> <p><it>Wndchrm </it>is an open source utility for biological image analysis. The software works by first extracting image content descriptors from the raw image, image transforms, and compound image transforms. Then, the most informative features are selected, and the feature vector of each image is used for classification and similarity measurement.</p> <p>Results</p> <p><it>Wndchrm </it>has been tested using several publicly available biological datasets, and provided results which are favorably comparable to the performance of task-specific algorithms developed for these datasets. The simple user interface allows researchers who are not knowledgeable in computer vision methods and have no background in computer programming to apply image analysis to their data.</p> <p>Conclusion</p> <p>We suggest that <it>wndchrm </it>can be effectively used for a wide range of biological image analysis tasks. Using <it>wndchrm </it>can allow scientists to perform automated biological image analysis while avoiding the costly challenge of implementing computer vision and pattern recognition algorithms.</p

The Effects of Irreversible Electroporation (IRE) on Nerves

Background: If a critical nerve is circumferentially involved with tumor, radical surgery intended to cure the cancer must sacrifice the nerve. Loss of critical nerves may lead to serious consequences. In spite of the impressive technical advancements in nerve reconstruction, complete recovery and normalization of nerve function is difficult to achieve. Though irreversible electroporation (IRE) might be a promising choice to treat tumors near or involved critical nerve, the pathophysiology of the nerve after IRE treatment has not be clearly defined. Methods: We applied IRE directly to a rat sciatic nerve to study the long term effects of IRE on the nerve. A sequence of 10 square pulses of 3800 V/cm, each 100 ms long was applied directly to rat sciatic nerves. In each animal of group I (IRE) the procedure was applied to produce a treated length of about 10 mm. In each animal of group II (Control) the electrodes were only applied directly on the sciatic nerve for the same time. Electrophysiological, histological, and functional studies were performed on immediately after and 3 days, 1 week, 3, 5, 7 and 10 weeks following surgery. Findings: Electrophysiological, histological, and functional results show the nerve treated with IRE can attain full recovery after 7 weeks. Conclusion: This finding is indicative of the preservation of nerve involving malignant tumors with respect to the application of IRE pulses to ablate tumors completely. In summary, IRE may be a promising treatment tool for any tumor involving nerves