Analyzing MRI scans to detect glioblastoma tumor using hybrid deep belief networks

Abstract Glioblastoma (GBM) is a stage 4 malignant tumor in which a large portion of tumor cells are reproducing and dividing at any moment. These tumors are life threatening and may result in partial or complete mental and physical disability. In this study, we have proposed a classification model using hybrid deep belief networks (DBN) to classify magnetic resonance imaging (MRI) for GBM tumor. DBN is composed of stacked restricted Boltzmann machines (RBM). DBN often requires a large number of hidden layers that consists of large number of neurons to learn the best features from the raw image data. Hence, computational and space complexity is high and requires a lot of training time. The proposed approach combines DTW with DBN to improve the efficiency of existing DBN model. The results are validated using several statistical parameters. Statistical validation verifies that the combination of DTW and DBN outperformed the other classifiers in terms of training time, space complexity and classification accuracy

Brain MRI Image Classification for Cancer Detection Using Deep Wavelet Autoencoder-Based Deep Neural Network

Technology and the rapid growth in the area of brain imaging technologies have forever made for a pivotal role in analyzing and focusing the new views of brain anatomy and functions. The mechanism of image processing has widespread usage in the area of medical science for improving the early detection and treatment phases. Deep neural networks (DNN), till date, have demonstrated wonderful performance in classification and segmentation task. Carrying this idea into consideration, in this paper, a technique for image compression using a deep wavelet autoencoder (DWA), which blends the basic feature reduction property of autoencoder along with the image decomposition property of wavelet transform is proposed. The combination of both has a tremendous effect on sinking the size of the feature set for enduring further classification task by using DNN. A brain image dataset was taken and the proposed DWA-DNN image classifier was considered. The performance criterion for the DWA-DNN classifier was compared with other existing classifiers such as autoencoder-DNN or DNN, and it was noted that the proposed method outshines the existing methods

Clusterin protects neurons against intracellular proteotoxicity.

It is now widely accepted in the field that the normally secreted chaperone clusterin is redirected to the cytosol during endoplasmic reticulum (ER) stress, although the physiological function(s) of this physical relocation remain unknown. We have examined in this study whether or not increased expression of clusterin is able to protect neuronal cells against intracellular protein aggregation and cytotoxicity, characteristics that are strongly implicated in a range of neurodegenerative diseases. We used the amyotrophic lateral sclerosis-associated protein TDP-43 as a primary model to investigate the effects of clusterin on protein aggregation and neurotoxicity in complementary in vitro, neuronal cell and Drosophila systems. We have shown that clusterin directly interacts with TDP-43 in vitro and potently inhibits its aggregation, and observed that in ER stressed neuronal cells, clusterin co-localized with TDP-43 and specifically reduced the numbers of cytoplasmic inclusions. We further showed that the expression of TDP-43 in transgenic Drosophila neurons induced ER stress and that co-expression of clusterin resulted in a dramatic clearance of mislocalized TDP-43 from motor neuron axons, partially rescued locomotor activity and significantly extended lifespan. We also showed that in Drosophila photoreceptor cells, clusterin co-expression gave ER stress-dependent protection against proteotoxicity arising from both Huntingtin-Q128 and mutant (R406W) human tau. We therefore conclude that increased expression of clusterin can provide an important defense against intracellular proteotoxicity under conditions that mimic specific features of neurodegenerative disease

The Clusterin Enigma: Structure and Function Studies of the First Known Mammalian Secreted Chaperone

Proteostasis refers to a crucial act of fine-tuning the synthesis, folding, localisation and degradation of proteins, and this balance must be maintained both inside and outside cells. Clusterin (CLU) is the best characterised secreted mammalian chaperone that is a key component of extracellular proteostasis - it binds to misfolding proteins to stabilise them in a soluble state, inhibit their aggregation, and facilitate their clearance by cellular uptake and degradation. CLU has been shown to potently inhibit the aggregation of misfolding proteins that form both amorphous and amyloid aggregates. CLU is a disulphide-linked heterodimer that in solution exists in a range of different oligomeric states (monomer, dimer and higher multimers) which may be important in its chaperone action. However, the lack of a known three-dimensional structure for CLU and limited information about its secondary structures have been major roadblocks in identifying regions of the molecule that play critical roles in its biological functions. Furthermore, preliminary evidence indicates that during ER stress the intracellular trafficking of CLU deviates from the secretory pathway and CLU is released into the cytosol. However, there is very limited information about the mechanism of CLU release to the cytosol, or its biological roles in cells undergoing ER stress. The work summarised in this thesis suggests that (i) residues 360-427 in the CLU β-chain C terminus contain elements that are likely to be critical for self-oligomerisation of CLU heterodimers, and (ii) residues 347-354 and 420-427 are critical for binding to misfolded proteins and inhibiting their aggregation to form either amorphous aggregates or amyloid. Furthermore, the results also show that in ER stressed cells, CLU that is released to the cytosol contains an intact N-terminus similar to secreted CLU, and is comprised of both uncleaved and cleaved variants (probably released from the ER and Golgi respectively). Further findings are that CLU release to the cytosol is via the N-End Rule pathway, being dependent upon the expression of arginyl transferase 1 (encoded by ATE1) and CLU residues D1 and D6 (which may act as N-degrons). The results also suggest that cytosolic CLU forms complexes with misfolded proteins in the cytosol and traffics these to proteasomes and autophagosomes for degradation. Collectively, the results provide very significant new information about the structure-function relations of CLU and substantively extend understanding of an important role of cytosolic CLU as a key player in intracellular proteostasis during ER stress. In the longer term, these results may provide parts of the necessary foundation upon which novel therapies using CLU can be developed in the future to treat serious human diseases, including Alzheimer’s disease, systemic amyloidosis, preeclampsia, cancers and dry eye diseases

Rapid high-yield expression and purification of fully post-translationally modified recombinant clusterin and mutants

The first described and best known mammalian secreted chaperone, abundant in human blood, is clusterin. Recent independent studies are now exploring the potential use of clusterin as a therapeutic in a variety of disease contexts. In the past, the extensive post-translational processing of clusterin, coupled with its potent binding to essentially any misfolded protein, have meant that its expression as a fully functional recombinant protein has been very difficult. We report here the first rapid and high-yield system for the expression and purification of fully post-translationally modified and chaperone-active clusterin. Only 5–6 days is required from initial transfection to harvest of the protein-free culture medium containing the recombinant product. Purification to near-homogeneity can then be accomplished in a single affinity purification step and the yield for wild type human clusterin is of the order of 30–40 mg per litre of culture. We have also shown that this system can be used to quickly express and purify custom-designed clusterin mutants. These advances dramatically increase the feasibility of detailed structure–function analysis of the clusterin molecule and will facilitate identification of those specific regions responsible for the interactions of clusterin with receptors and other molecules

Altercating Leishmaniasis:Cultivating Improved Vaccines

Abstract The exponentially rising cases of Leishmaniasis over the past decades, has attracted scientists and clinicians to mitigate the contagious infection by modern treatments and new generation vaccinations. Leishmania, the causative pathogen of this infection predominantly expresses its diseased condition in form of cutaneous leishmaniasis. Although systemic leishmaniasis, is a more deadly form, but cases of its manifestation are limited; thereby staging the focus onto more intricate study of cutaneous leishmaniasis. Designing a vaccine against Leishmania has witnessed more than two generations of vaccine, but each attempt has failed more than it's cases of success. The proposed drawbacks root to the difficulty in ensuring an efficient transition of research from simple laboratory experiments carried out in-vitro/in-vivo in small animals to that of the humans. There have been extensive case studies of this disease and thus every immunological aspect has been our focus. This paper is an attempt to decipher the ideas and methodologies adopted till date and further target the genetic spans and molecular moieties, for crafting an alternative vaccine based on efforts to mock the pathogenic pathways

Roles of constitutively secreted extracellular chaperones in neuronal cell repair and regeneration

Protein quality control involves many processes that jointly act to regulate the expression, localization, turnover, and degradation of proteins, and has been highlighted in recent studies as critical to the differentiation of stem cells during regeneration. The roles of constitutively secreted extracellular chaperones in neuronal injury and disease are poorly understood. Extracellular chaperones are multifunctional proteins expressed by many cell types, including those of the nervous system, known to facilitate protein quality control processes. These molecules exert pleiotropic effects and have been implicated as playing important protective roles in a variety of stress conditions, including tissue damage, infections, and local tissue inflammation. This article aims to provide a critical review of what is currently known about the functions of extracellular chaperones in neuronal repair and regeneration and highlight future directions for this important research area. We review what is known of four constitutively secreted extracellular chaperones directly implicated in processes of neuronal damage and repair, including transthyretin, clusterin, α2-macroglobulin, and neuroserpin, and propose that investigation into the effects of these and other extracellular chaperones on neuronal repair and regeneration has the potential to yield valuable new therapies