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[
Comput Biol Med,
2020]
Protein-protein interactions (PPIs) play a crucial role in biological processes of living organisms. Correct prediction of PPI can prove to be extremely valuable in probing protein functions which can aid in the development of new and powerful therapies for disease prevention. Many experimental studies have been previously performed to investigate PPIs. However, in-vitro techniques to investigate PPIs are resource-extensive and time-consuming. Although various in-silico approaches to predict PPI have been developed in recent years, they could be fallible in terms of accuracy and false-positive rate. To overcome these shortcomings, we propose a novel approach, AE-LGBM to predict the PPIs more accurately. It employs LightGBM classifier and utilizes the Autoencoder, which is an artificial neural network, to efficiently produce lower-dimensional, discriminative, and noise-free features. We incorporate conjoint triad (CT) and Composition-Transition-Distribution (CTD) features into the AE-LGBM framework. On performing ten-fold cross-validation, the prediction accuracies obtained by AE-LGBM for Human and Yeast datasets are 98.7% and 95.4% respectively. AE-LGBM was further evaluated on independent datasets and has achieved excellent accuracies of 100%, 100%, 99.9%, 99.3%, 99.2% on E. coli, M. musculus, C. elegans, H. pylori and H. sapiens respectively. AE-LGBM has also obtained the best accuracy when tested over three important PPI networks namely single-core network (CD9), the multiple-core network (The Ras/Raf/MEK/ERK pathway) and the cross-connection network (Wnt Network). The outstanding generalization ability of AE-LGBM makes it a versatile, efficient, and robust PPIs prediction model.
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[
Genetics,
2013]
Here we provide the first genome-wide in vivo analysis of the Na+/Ca2+ exchanger family in the model system Caenorhabditis elegans. We source all members of this family within the Caenorhabditis genus and reconstruct their phylogeny across humans and Drosophila melanogaster. Next, we provide a description of the expression pattern for each exchanger gene in C. elegans, revealing a wide expression in a number of tissues and cell types including sensory neurons, interneurons, motor neurons, muscle cells, and intestinal tissue. Finally, we conduct a series of behavioral and functional analyses through mutant characterization in C. elegans. From these data we demonstrate that, similar to mammalian systems, the expression of Na+/Ca2+ exchangers in C. elegans is skewed toward excitable cells, and we propose that C. elegans may be an ideal model system for the study of Na+/Ca2+ exchangers.
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Askjaer, Peter, Meister, Peter, Gomez-Saldivar, Georgina, van Steensel, Bas, Kind, Jop, Sharma, Rahul
[
International Worm Meeting,
2013]
During development and differentiation, the genome gets progressively organized inside the nuclear space. The function of genome nuclear organization remains elusive, although a number of human diseases are linked to mutations in structural elements of the nucleus. Decreasing mobility of chromatin and chromatin factors moreover correlates with loss of differentiation potential, suggesting chromatin plasticity could be an integral part of pluripotency. Similarly to mammalian cells, the worm genome gets partitioned during cell fate acquisition into active and silent domains inside the nuclear space. In C. elegans current data suggest that the nuclear interior is a rather active domain, while the nuclear periphery is a mosaic of active and silent compartments. The dynamics of these domains during physiological challenges, cell fate determination or during organismal aging is however poorly understood. Genomic characterization of subnuclear domains has been achieved using damID, a technique in which a fusion protein between the E. coli adenine methyltransferase dam is fused to a nuclear protein specific of the nuclear compartment of interest. Adenines in genomic stretches proximal to this protein are methylated and this can be detected using microarrays or sequencing. damID has been successfully used to uncover DAF-16 target genes, but also the nuclear organization of chromosomes relative to the nuclear lamina using a dam fusion to LMN-1, the unique worm lamin. Using a newly developed methylated adenine binder, we are now able to track in vivo nuclear compartments in developing and aging worms. We will present this system in the worm as well as the first results on dynamics of subnuclear compartments in aging or physiologically challenged worms.
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[
Front Immunol,
2018]
Filarial parasites suppress, divert, or polarize the host immune response to aid their survival. However, mechanisms that govern the polarization of host Ms during early filarial infection are not completely understood. In this study, we infected BALB/c mice with infective larvae stage-3 of<i>Brugia malayi</i>(Bm-L3) and studied their effect on the polarization of splenic Ms. Results showed that Ms displayed M2-phenotype by day 3 p.i. characterized by upregulated IL-4, but reduced IL-12 and Prostaglandin-D2 secretion. Increased arginase activity, higher arginase-1 but reduced NOS2 expression and poor phagocytic and antigen processing capacity was also observed. M2 Ms supported T-cell proliferation and characteristically upregulated p-ERK but downregulated NF-B-
p65 and NF-B-
p50/105. Notably, Bm-L3 synergized with host regulatory T-cells (Tregs) and polarized M2 Ms to regulatory Ms (Mregs) by day 7 p.i., which secreted copious amounts of IL-10 and prostaglandin-E2. Mregs also showed upregulated expression levels of MHC-II, CD80, and CD86 and exhibited increased antigen-processing capacity but displayed impaired activation of NF-B-
p65 and NF-B-
p50/105. Neutralization of Tregs by anti-GITR+anti-CD25 antibodies checked the polarization of M2 Ms to Mregs, decreased accumulation of regulatory B cells and inflammatory monocytes, and reduced secretion of IL-10, but enhanced IL-4 production and percentages of eosinophils, which led to Bm-L3 killing. In summary, we report hitherto undocumented effects of early Bm-L3 infection on the polarization of splenic Ms and show how infective larvae deftly utilize the functional plasticity of host Ms to establish themselves inside the host.
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[
Rev Sci Tech,
2017]
Dogs play valuable roles in human society. In addition to serving as pets and companions, dogs have also been important in hunting and, in recent times, as therapy animals. In India, the number of pet dogs is estimated to be around 5 million. The stray dog population in India is estimated to be 19 million and still increasing, due to ineffective control measures. Stray dogs pose substantial risks to public health due to injury and transmission of zoonoses such as rabies. Both pet and stray dogs may act as reservoirs of zoonotic parasites in India, which has a climate conducive to the environmental survival and transmission of many zoonotic parasites. At present, visceral larva migrans, cutaneous larva migrans and echinococcosis are the most important parasitic zoonoses in India. Leishmaniosis, dirofilariosis, Brugia malayi infection and giardiosis are potentially significant emerging parasitic zoonoses, and theleziosis, gnathostomiosis and dipylidiosis occur sporadically. Because of their biomedical and public health significance, and the lack of literature and compiled data on parasitic zoonoses of dogs in India, the authors provide a concise review on this topic along with potential control strategies.
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[
Curr Opin Cell Biol,
2013]
With its invariant cell lineage, easy genetics and small genome, the nematode Caenorhabditis elegans has emerged as one of the prime models in developmental biology over the last 50 years. Surprisingly however, until a decade ago very little was known about nuclear organization in worms, even though it is an ideal model system to explore the link between nuclear organization and cell fate determination. Here, we review the latest findings that exploit the repertoire of genetic tools developed in worms, leading to the identification of important sequences and signals governing the changes in chromatin tridimensional architecture. We also highlight parallels and differences to other model systems.
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[
Genesis,
2014]
Maintenance of calcium homeostasis is necessary for the development and survival of all animals. Calcium ions modulate excitability and bind effectors capable of initiating many processes such as muscular contraction and neurotransmission. However, excessive amounts of calcium in the cytosol or within intracellular calcium stores can trigger apoptotic pathways in cells that have been implicated in cardiac and neuronal pathologies. Accordingly, it is critical for cells to rapidly and effectively regulate calcium levels. The Na(+) /Ca(2+) exchangers (NCX), Na(+) /Ca(2+) /K(+) exchangers (NCKX), and Ca(2+) /Cation exchangers (CCX) are the three classes of sodium calcium antiporters found in animals. These exchanger proteins utilize an electrochemical gradient to extrude calcium. Although they have been studied for decades, much is still unknown about these proteins. In this review, we examine current knowledge about the structure, function, and physiology and also discuss their implication in various developmental disorders. Finally, we highlight recent data characterizing the family of sodium calcium exchangers in the model system, Caenorhabditis elegans, and propose that C. elegans may be an ideal model to complement other systems and help fill gaps in our knowledge of sodium calcium exchange biology.
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[
Aging, Metabolism, Stress, Pathogenesis, and Small RNAs, Madison, WI,
2010]
Understanding the cellular mechanisms of heavy metal (e.g. cadmium [Cd], mercury [Hg] and lead [Pb]) detoxification is critical for the cure of heavy metal-caused diseases, such as neurodegenerative conditions, dysfunction of vital organs, and cancer. Among the major contributors to heavy metal detoxification are members of one of the largest,structurally conserved and functionally diverse family of integral membrane proteins, ATP-binding cassette (ABC) transporters. Canonical,""full-molecule"", ABC transporters consist of two transmembrane domains (TMD) and two ATP-binding domains (NBD). ""Half-molecule"" transporters contain a single TMD and NBD. The C. elegans genome encodes 61 ABC proteins, of which 25 are half-transporters. Full-molecule, MRP-1, PGP-1 and PGP-3 have been shown to detoxify Cd and As (Broeks et al 1996). We showed that a half-transporter, HMT-1, is acutely required for detoxification of Cd, As and Cu and is expressed in intestinal cells, head and tail neurons and coelomocytes (Vatamaniuk et al 2005; Schwartz et al 2010). Which other family members contribute to heavy metal detoxification and how ABC transporter-mediated metal detoxification pathways are related, are not known. Here we used knock-out mutant alleles and RNAi knockdown worms to systematically test the role of each family member in heavy metal detoxification. These screens identified 13 ABC transporters (4 half-transporters and 9 full-transporters), in addition to HMT-1, MRP-1, PGP-1 and PGP-3, that contribute to Cd detoxification. Effects of Cd on their transcript abundance and alternate transcript forms were then studied by q-RT-PCR or RNA-Seq technology. To distinguish Cd-specific from oxidative stress-induced changes in selected ABC transporter gene expression, the effect of Cd vs H2O2 was compared. Finally, the effect of mutations in selected ABC transporters on the ability of worms to accumulate Cd as well as other mineral elements was analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The results of these studies as well as relationship between different ABC-transporter metal detoxification pathways will be discussed.
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[
Bioinform Biol Insights,
2016]
Na(+)/Ca(2+) exchangers are low-affinity, high-capacity transporters that rapidly transport calcium against a gradient of Na(+) ions. Na(+)/Ca(2+) exchangers are divided into three groups based upon substrate specificity: Na(+)/Ca(2+) exchangers (NCX), Na(+)/Ca(2+)/K(+) exchangers (NCKX), and Ca(2+)/cation exchangers (NCLX). In mammals, there are three NCX genes, five NCKX genes, and a single NCLX gene. The genome of the nematode Caenorhabditis elegans contains 10 Na(+)/Ca(2+) exchanger genes: three NCX, five NCLX, and two NCKX genes. In a previous study, we characterized the structural and taxonomic specializations within the family of Na(+)/Ca(2+) exchangers across the phylum Nematoda and observed a complex picture of Na(+)/Ca(2+) exchanger evolution across diverse nematode species. We noted multiple cases of putative gene gain and loss and, most surprisingly, did not detect members of the NCLX type of exchangers within subsets of nematode species. In this commentary, we discuss these findings and speculate on the functional outcomes and physiology of these observations. Our data highlight the importance of studying diverse systems in order to get a deeper understanding of the evolution and regulation of Ca(2+) signaling critical for animal function.
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[
Eur J Pharmacol,
2017]
Alzheimer's disease is a common neurodegenerative disorder which is characterized by the presence of beta- amyloid protein and neurofibrillary tangles (NFTs) in the brain. Till now, various higher vertebrate models have been in use to study the pathophysiology of this disease. But, these models possess some limitations like ethical restrictions, high cost, difficult maintenance of large quantity and lesser reproducibility. Besides, various lower chordate animals like Danio rerio, Drosophila melanogaster, Caenorhabditis elegans and Ciona intestinalis have been proved to be an important model for the in vivo determination of targets of drugs with least limitations. In this article, we reviewed different studies conducted on theses models for the better understanding of the pathophysiology of AD and their subsequent application as a potential tool in the preclinical evaluation of new drugs.