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Frontiers in Molecular Biosciences

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https://www.readbyqxmd.com/read/28932739/agonist-binding-to-chemosensory-receptors-a-systematic-bioinformatics-analysis
#1
Fabrizio Fierro, Eda Suku, Mercedes Alfonso-Prieto, Alejandro Giorgetti, Sven Cichon, Paolo Carloni
Human G-protein coupled receptors (hGPCRs) constitute a large and highly pharmaceutically relevant membrane receptor superfamily. About half of the hGPCRs' family members are chemosensory receptors, involved in bitter taste and olfaction, along with a variety of other physiological processes. Hence these receptors constitute promising targets for pharmaceutical intervention. Molecular modeling has been so far the most important tool to get insights on agonist binding and receptor activation. Here we investigate both aspects by bioinformatics-based predictions across all bitter taste and odorant receptors for which site-directed mutagenesis data are available...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28894739/immune-modulating-activity-of-hydrogel-microparticles-contributes-to-the-host-defense-in-a-murine-model-of-cutaneous-anthrax
#2
Allison L Teunis, Taissia G Popova, Virginia Espina, Lance A Liotta, Serguei G Popov
We recently reported that the open-mesh (0.7 μ) polyacrylamide microparticles (MPs) with internally-coupled Cibacron affinity dye demonstrate protective effect in mice challenged into footpads with high doses (200 LD50) of anthrax (Sterne) spores. A single injection of MPs before spore challenge reduces inflammatory response, delays onset of mortality and promotes survival. In this study, we show that the effect of MPs was substantially increased at the lower spore dose (7 LD50). The inflammation of footpads was reduced to the background level, and 60% of animals survived for 16 days while all untreated infected animals died within 6 days with strong inflammation...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28884116/the-role-of-pontin-and-reptin-in-cellular-physiology-and-cancer-etiology
#3
REVIEW
Yu-Qian Mao, Walid A Houry
Pontin (RUVBL1, TIP49, TIP49a, Rvb1) and Reptin (RUVBL2, TIP48, TIP49b, Rvb2) are highly conserved ATPases of the AAA+ (ATPases Associated with various cellular Activities) superfamily and are involved in various cellular processes that are important for oncogenesis. First identified as being upregulated in hepatocellular carcinoma and colorectal cancer, their overexpression has since been shown in multiple cancer types such as breast, lung, gastric, esophageal, pancreatic, kidney, bladder as well as lymphatic, and leukemic cancers...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28879185/increased-potency-of-a-bi-specific-tl1a-adam17-tace-inhibitor-by-cell-surface-targeting
#4
Tomer Weizman, Itay Levin, Marianna Zaretsky, Irit Sagi, Amir Aharoni
Inflammatory bowel disease (IBD) is a multifactorial disease characterized by the dysregulated activity of many pro-inflammatory factors. Thus, bi-specific inhibitors for the simultaneous inhibition of two pro-inflammatory factors can exhibit high therapeutic potential. Here, we developed a novel bi-specific inhibitor targeting the TL1A cytokine and ADAM17/TACE metalloprotease. Biochemical analysis of the bi-specific inhibitor revealed high TL1A binding and TACE inhibition that is similar to the two respective mono-specific inhibitors...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28879184/hsp78-78-kda-heat-shock-protein-a-representative-aaa-family-member-found-in-the-mitochondrial-matrix-of-saccharomyces-cerevisiae
#5
REVIEW
Josielle Abrahão, David Z Mokry, Carlos H I Ramos
ATPases associated with diverse cellular activities (AAA+) form a superfamily of proteins involved in a variety of functions and are characterized by the presence of an ATPase module containing two conserved motifs known as Walker A and Walker B. ClpB and Hsp104, chaperones that have disaggregase activities, are members of a subset of this superfamily, known as the AAA family, and are characterized by the presence of a second highly conserved motif, known as the second region of homology (SRH). Hsp104 and its homolog Hsp78 (78 kDa heat shock protein) are representatives of the Clp family in yeast...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28879183/deep-sequencing-transcriptome-analysis-of-murine-wound-healing-effects-of-a-multicomponent-multitarget-natural-product-therapy-tr14
#6
Georges St Laurent, Bernd Seilheimer, Michael Tackett, Jianhua Zhou, Dmitry Shtokalo, Yuri Vyatkin, Maxim Ri, Ian Toma, Dan Jones, Timothy A McCaffrey
Wound healing involves an orchestrated response that engages multiple processes, such as hemostasis, cellular migration, extracellular matrix synthesis, and in particular, inflammation. Using a murine model of cutaneous wound repair, the transcriptome was mapped from 12 h to 8 days post-injury, and in response to a multicomponent, multi-target natural product, Tr14. Using single-molecule RNA sequencing (RNA-seq), there were clear temporal changes in known transcripts related to wound healing pathways, and additional novel transcripts of both coding and non-coding genes...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28848737/lysine-directed-post-translational-modifications-of-tau-protein-in-alzheimer-s-disease-and-related-tauopathies
#7
REVIEW
Christiana Kontaxi, Pedro Piccardo, Andrew C Gill
Tau is a microtubule-associated protein responsible mainly for stabilizing the neuronal microtubule network in the brain. Under normal conditions, tau is highly soluble and adopts an "unfolded" conformation. However, it undergoes conformational changes resulting in a less soluble form with weakened microtubule stabilizing properties. Altered tau forms characteristic pathogenic inclusions in Alzheimer's disease and related tauopathies. Although, tau hyperphosphorylation is widely considered to be the major trigger of tau malfunction, tau undergoes several post-translational modifications at lysine residues including acetylation, methylation, ubiquitylation, SUMOylation, and glycation...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28824921/bardet-biedl-syndrome-as-a-chaperonopathy-dissecting-the-major-role-of-chaperonin-like-bbs-proteins-bbs6-bbs10-bbs12
#8
REVIEW
María Álvarez-Satta, Sheila Castro-Sánchez, Diana Valverde
Bardet-Biedl syndrome (BBS) is a rare genetic disorder that belongs to the group of ciliopathies, defined as diseases caused by defects in cilia structure and/or function. The six diagnostic features considered for this syndrome include retinal dystrophy, obesity, polydactyly, cognitive impairment and renal and urogenital anomalies. Furthermore, three of the 21 genes currently known to be involved in BBS encode chaperonin-like proteins (MKKS/BBS6, BBS10, and BBS12), so BBS can be also considered a member of the growing group of chaperonopathies...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28824920/comparative-analysis-of-the-structure-and-function-of-aaa-motors-clpa-clpb-and-hsp104-common-threads-and-disparate-functions
#9
REVIEW
Elizabeth C Duran, Clarissa L Weaver, Aaron L Lucius
Cellular proteostasis involves not only the expression of proteins in response to environmental needs, but also the timely repair or removal of damaged or unneeded proteins. AAA+ motor proteins are critically involved in these pathways. Here, we review the structure and function of AAA+ proteins ClpA, ClpB, and Hsp104. ClpB and Hsp104 rescue damaged proteins from toxic aggregates and do not partner with any protease. ClpA functions as the regulatory component of the ATP dependent protease complex ClpAP, and also remodels inactive RepA dimers into active monomers in the absence of the protease...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28798917/corrigendum-biomarkers-and-algorithms-for-the-diagnosis-of-vitamin-b12-deficiency
#10
Luciana Hannibal, Vegard Lysne, Anne-Lise Bjørke-Monsen, Sidney Behringer, Sarah C Grünert, Ute Spiekerkoetter, Donald W Jacobsen, Henk J Blom
[This corrects the article on p. 27 in vol. 3, PMID: 27446930.].
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28791296/metabolomics-and-proteomics-of-brassica-napus-guard-cells-in-response-to-low-co2
#11
Sisi Geng, Bing Yu, Ning Zhu, Craig Dufresne, Sixue Chen
Stomatal guard cell response to various stimuli is an important process that balances plant carbon dioxide (CO2) uptake and water transpiration. Elevated CO2 induces stomatal closure, while low CO2 promotes stomatal opening. The signaling process of elevated CO2 induced stomatal closure has been extensively studied in recent years. However, the mechanism of low CO2 induced stomatal opening is not fully understood. Here we report metabolomic and proteomic responses of Brassica napus guard cells to low CO2 using hyphenated mass spectrometry technologies...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28785557/the-implications-and-future-perspectives-of-nanomedicine-for-cancer-stem-cell-targeted-therapies
#12
REVIEW
Vimal K Singh, Abhishek Saini, Ramesh Chandra
Cancer stem cells (CSCs) are believed to exhibit distinctive self-renewal, proliferation, and differentiation capabilities, and thus play a significant role in various aspects of cancer. CSCs have significant impacts on the progression of tumors, drug resistance, recurrence and metastasis in different types of malignancies. Due to their primary role, most researchers have focused on developing anti-CSC therapeutic strategies, and tremendous efforts have been put to explore methods for selective eradication of these therapeutically resistant CSCs...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28770210/extracellular-vesicles-tunneling-nanotubes-and-cellular-interplay-synergies-and-missing-links
#13
REVIEW
Muhammad Nawaz, Farah Fatima
The process of intercellular communication seems to have been a highly conserved evolutionary process. Higher eukaryotes use several means of intercellular communication to address both the changing physiological demands of the body and to fight against diseases. In recent years, there has been an increasing interest in understanding how cell-derived nanovesicles, known as extracellular vesicles (EVs), can function as normal paracrine mediators of intercellular communication, but can also elicit disease progression and may be used for innovative therapies...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28770209/aaa-machines-of-protein-destruction-in-mycobacteria
#14
REVIEW
Adnan Ali H Alhuwaider, David A Dougan
The bacterial cytosol is a complex mixture of macromolecules (proteins, DNA, and RNA), which collectively are responsible for an enormous array of cellular tasks. Proteins are central to most, if not all, of these tasks and as such their maintenance (commonly referred to as protein homeostasis or proteostasis) is vital for cell survival during normal and stressful conditions. The two key aspects of protein homeostasis are, (i) the correct folding and assembly of proteins (coupled with their delivery to the correct cellular location) and (ii) the timely removal of unwanted or damaged proteins from the cell, which are performed by molecular chaperones and proteases, respectively...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28748187/de-novo-assembly-and-characterization-of-cajanus-scarabaeoides-l-thouars-transcriptome-by-paired-end-sequencing
#15
Deepti Nigam, Swati Saxena, G Ramakrishna, Archana Singh, N K Singh, Kishor Gaikwad
Pigeonpea [Cajanus cajan (L.) Millsp.] is a heat and drought resilient legume crop grown mostly in Asia and Africa. Pigeonpea is affected by various biotic (diseases and insect pests) and abiotic stresses (salinity and water logging) which limit the yield potential of this crop. However, resistance to all these constraints is not readily available in the cultivated genotypes and some of the wild relatives have been found to withstand these resistances. Thus, the utilization of crop wild relatives (CWR) in pigeonpea breeding has been effective in conferring resistance, quality and breeding efficiency traits to this crop...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28748186/functional-diversity-of-aaa-protease-complexes-in-bacillus-subtilis
#16
REVIEW
Alexander K W Elsholz, Marlene S Birk, Emmanuelle Charpentier, Kürşad Turgay
Here, we review the diverse roles and functions of AAA+ protease complexes in protein homeostasis, control of stress response and cellular development pathways by regulatory and general proteolysis in the Gram-positive model organism Bacillus subtilis. We discuss in detail the intricate involvement of AAA+ protein complexes in controlling sporulation, the heat shock response and the role of adaptor proteins in these processes. The investigation of these protein complexes and their adaptor proteins has revealed their relevance for Gram-positive pathogens and their potential as targets for new antibiotics...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28736730/new-insight-into-microrna-functions-in-cancer-oncogene-microrna-tumor-suppressor-gene-network
#17
REVIEW
Kecheng Zhou, Minxia Liu, Yi Cao
Tumorigenesis is a multi-step and complex process with multi-factors involved. Deregulated oncogenes and tumor suppressor genes (TSGs) induced by genetic and epigenetic factors are considered as the driving force in the development and progression of cancer. Besides, microRNAs (miRNAs) act vital roles in tumorigenesis through regulating some oncogenes and TSGs. Interestingly, miRNAs are also regulated by oncogenes and TSGs. Considering the entangled regulation, here we propose a new insight into these regulation relationships in cancer: oncogene-miRNA-TSG network, which further emphasizes roles of miRNA, as well as highlights the network regulation among oncogene, miRNA, and TSG during tumorigenesis...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28713815/bioinformatic-prediction-of-possible-targets-and-mechanisms-of-action-of-the-green-tea-compound-epigallocatechin-3-gallate-against-breast-cancer
#18
Xinqiang Song, Mu Zhang, Lei Chen, Qingsong Lin
Epigallocatechin-3-gallate (EGCG), a bioactive compound in green tea, is the most abundant and biologically active catechin, and it exerts multiple effects in humans through mechanisms that remain to be clarified. The present study used bioinformatics to identify possible mechanisms by which EGCG reduces risk of breast cancer. Possible human protein targets of EGCG were identified in the PubChem database, possible human gene targets were identified in the NCBI database, and then both sets of targets were analyzed using Ingenuity Pathway Analysis to predict molecular networks affected by EGCG in breast cancer...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28676851/aaa-atpases-in-protein-degradation
#19
REVIEW
Ravikiran S Yedidi, Petra Wendler, Cordula Enenkel
Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28664160/new-techniques-for-ancient-proteins-direct-coupling-analysis-applied-on-proteins-involved-in-iron-sulfur-cluster-biogenesis
#20
Marco Fantini, Duccio Malinverni, Paolo De Los Rios, Annalisa Pastore
Direct coupling analysis (DCA) is a powerful statistical inference tool used to study protein evolution. It was introduced to predict protein folds and protein-protein interactions, and has also been applied to the prediction of entire interactomes. Here, we have used it to analyze three proteins of the iron-sulfur biogenesis machine, an essential metabolic pathway conserved in all organisms. We show that DCA can correctly reproduce structural features of the CyaY/frataxin family (a protein involved in the human disease Friedreich's ataxia) despite being based on the relatively small number of sequences allowed by its genomic distribution...
2017: Frontiers in Molecular Biosciences
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