scholarly journals OlfactionBase: a repository to explore odors, odorants, olfactory receptors and odorant–receptor interactions

2021 ◽  
Author(s):  
Anju Sharma ◽  
Bishal Kumar Saha ◽  
Rajnish Kumar ◽  
Pritish Kumar Varadwaj

Abstract Olfaction is a multi-stage process that initiates with the odorants entering the nose and terminates with the brain recognizing the odor associated with the odorant. In a very intricate way, the process incorporates various components functioning together and in synchronization. OlfactionBase is a free, open-access web server that aims to bring together knowledge about many aspects of the olfaction mechanism in one place. OlfactionBase contains detailed information of components like odors, odorants, and odorless compounds with physicochemical and ADMET properties, olfactory receptors (ORs), odorant- and pheromone binding proteins, OR-odorant interactions in Human and Mus musculus. The dynamic, user-friendly interface of the resource facilitates exploration of different entities: finding chemical compounds having desired odor, finding odorants associated with OR, associating chemical features with odor and OR, finding sequence information of ORs and related proteins. Finally, the data in OlfactionBase on odors, odorants, olfactory receptors, human and mouse OR-odorant pairs, and other associated proteins could aid in the inference and improved understanding of odor perception, which might provide new insights into the mechanism underlying olfaction. The OlfactionBase is available at https://bioserver.iiita.ac.in/olfactionbase/

2002 ◽  
Vol 2 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Kevin Culligan ◽  
Kay Ohlendieck

Duchenne muscular dystrophy (DMD), the most common inherited neuromuscular disorder, is characterized by progressive muscle wasting and weakness. One third of Duchenne patients suffer a moderate to severe, nonprogressive form of mental retardation. Mutations in the DMD gene are thought to be responsible, with the shorter isoforms of dystrophin implicated in its molecular brain pathogenesis. It is becoming clear that region-specific variations in dystrophin isoforms delegate the composition of the dystrophin-glycoprotein complex in brain, and hence, the function of the specific membrane assembly. Here we summarize the recent advances in the understanding of brain dystrophin, dystrophin-related proteins and dystrophin-associated proteins.


2019 ◽  
Vol 24 (34) ◽  
pp. 4013-4022 ◽  
Author(s):  
Xiang Cheng ◽  
Xuan Xiao ◽  
Kuo-Chen Chou

Knowledge of protein subcellular localization is vitally important for both basic research and drug development. With the avalanche of protein sequences emerging in the post-genomic age, it is highly desired to develop computational tools for timely and effectively identifying their subcellular localization based on the sequence information alone. Recently, a predictor called “pLoc-mPlant” was developed for identifying the subcellular localization of plant proteins. Its performance is overwhelmingly better than that of the other predictors for the same purpose, particularly in dealing with multi-label systems in which some proteins, called “multiplex proteins”, may simultaneously occur in two or more subcellular locations. Although it is indeed a very powerful predictor, more efforts are definitely needed to further improve it. This is because pLoc-mPlant was trained by an extremely skewed dataset in which some subsets (i.e., the protein numbers for some subcellular locations) were more than 10 times larger than the others. Accordingly, it cannot avoid the biased consequence caused by such an uneven training dataset. To overcome such biased consequence, we have developed a new and bias-free predictor called pLoc_bal-mPlant by balancing the training dataset. Cross-validation tests on exactly the same experimentconfirmed dataset have indicated that the proposed new predictor is remarkably superior to pLoc-mPlant, the existing state-of-the-art predictor in identifying the subcellular localization of plant proteins. To maximize the convenience for the majority of experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc_bal-mPlant/, by which users can easily get their desired results without the need to go through the detailed mathematics.


2019 ◽  
Vol 15 (5) ◽  
pp. 472-485 ◽  
Author(s):  
Kuo-Chen Chou ◽  
Xiang Cheng ◽  
Xuan Xiao

<P>Background/Objective: Information of protein subcellular localization is crucially important for both basic research and drug development. With the explosive growth of protein sequences discovered in the post-genomic age, it is highly demanded to develop powerful bioinformatics tools for timely and effectively identifying their subcellular localization purely based on the sequence information alone. Recently, a predictor called “pLoc-mEuk” was developed for identifying the subcellular localization of eukaryotic proteins. Its performance is overwhelmingly better than that of the other predictors for the same purpose, particularly in dealing with multi-label systems where many proteins, called “multiplex proteins”, may simultaneously occur in two or more subcellular locations. Although it is indeed a very powerful predictor, more efforts are definitely needed to further improve it. This is because pLoc-mEuk was trained by an extremely skewed dataset where some subset was about 200 times the size of the other subsets. Accordingly, it cannot avoid the biased consequence caused by such an uneven training dataset. </P><P> Methods: To alleviate such bias, we have developed a new predictor called pLoc_bal-mEuk by quasi-balancing the training dataset. Cross-validation tests on exactly the same experimentconfirmed dataset have indicated that the proposed new predictor is remarkably superior to pLocmEuk, the existing state-of-the-art predictor in identifying the subcellular localization of eukaryotic proteins. It has not escaped our notice that the quasi-balancing treatment can also be used to deal with many other biological systems. </P><P> Results: To maximize the convenience for most experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/pLoc_bal-mEuk/. </P><P> Conclusion: It is anticipated that the pLoc_bal-Euk predictor holds very high potential to become a useful high throughput tool in identifying the subcellular localization of eukaryotic proteins, particularly for finding multi-target drugs that is currently a very hot trend trend in drug development.</P>


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shawn Gu ◽  
Tijana Milenković

Abstract Background Network alignment (NA) can transfer functional knowledge between species’ conserved biological network regions. Traditional NA assumes that it is topological similarity (isomorphic-like matching) between network regions that corresponds to the regions’ functional relatedness. However, we recently found that functionally unrelated proteins are as topologically similar as functionally related proteins. So, we redefined NA as a data-driven method called TARA, which learns from network and protein functional data what kind of topological relatedness (rather than similarity) between proteins corresponds to their functional relatedness. TARA used topological information (within each network) but not sequence information (between proteins across networks). Yet, TARA yielded higher protein functional prediction accuracy than existing NA methods, even those that used both topological and sequence information. Results Here, we propose TARA++ that is also data-driven, like TARA and unlike other existing methods, but that uses across-network sequence information on top of within-network topological information, unlike TARA. To deal with the within-and-across-network analysis, we adapt social network embedding to the problem of biological NA. TARA++ outperforms protein functional prediction accuracy of existing methods. Conclusions As such, combining research knowledge from different domains is promising. Overall, improvements in protein functional prediction have biomedical implications, for example allowing researchers to better understand how cancer progresses or how humans age.


Marine Drugs ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 131
Author(s):  
Seon Kyeong Park ◽  
Jin Yong Kang ◽  
Jong Min Kim ◽  
Hyun-Jin Kim ◽  
Ho Jin Heo

To evaluate the effects of Ecklonia cava (E. cava) on ambient-pollution-induced neurotoxicity, we used a mouse model exposed to particulate matter smaller than 2.5 µm in aerodynamic diameter (PM2.5). The intake of water extract from E. cava (WEE) effectively prevented the learning and memory decline. After a behavioral test, the toll-like receptor (TLR)-4-initiated inflammatory response was confirmed by PM2.5 exposure in the lung and brain tissues, and the WEE was regulated through the inhibition of nuclear factor-kappa B (NF-κB)/inflammasome formation signaling pathway and pro-inflammatory cytokines (IL-6 and IFN-γ). The WEE also effectively improved the PM2.5-induced oxidative damage of the lungs and brain through the inhibition of malondialdehyde (MDA) production and the activation of mitochondrial activity (mitochondrial ROS content, mitochondria membrane potential (MMP), adenosine triphosphate (ATP) content, and mitochondria-mediated apoptotic molecules). In particular, the WEE regulated the cognition-related proteins (a decreased amyloid precursor protein (APP) and p-Tau, and an increased brain-derived neurotrophic factor (BDNF)) associated with PM2.5-induced cognitive dysfunction. Additionally, the WEE prevented the inactivation of acetylcholine (ACh) synthesis and release as a neurotransmitter by regulating the acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT), and ACh receptor (AChR)-α3 in the brain tissue. The bioactive compounds of the WEE were detected as the polysaccharide (average Mw; 160.13 kDa) and phenolic compounds including 2′-phloroeckol.


2021 ◽  
Vol 22 (4) ◽  
pp. 1834
Author(s):  
Tomoko Okada ◽  
Toshihiko Ogura

Autophagy is an intracellular self-devouring system that plays a central role in cellular recycling. The formation of functional autophagosomes depends on several autophagy-related proteins, including the microtubule-associated proteins 1A/1B light chain 3 (LC3) and the conserved autophagy-related gene 12 (Atg12). We have recently developed a novel scanning electron-assisted dielectric microscope (SE-ADM) for nanoscale observations of intact cells. Here, we used the SE-ADM system to observe LC3- and Atg12-containing autophagosomes in cells labelled in the culture medium with antibodies conjugated to colloidal gold particles. We observed that, during autophagosome formation, Atg12 localized along the actin meshwork structure, whereas LC3 formed arcuate or circular alignments. Our system also showed a difference in the distribution of LC3 and Atg12; Atg12 was broadly distributed while LC3 was more localized. The difference in the spatial distribution demonstrated by our system explains the difference in the size of fluorescent spots due to the fluorescently labelled antibodies observed using optical microscopy. The direct SE-ADM observation of cells should thus be effective in analyses of autophagosome formation.


F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 84 ◽  
Author(s):  
Sisi Chen ◽  
Charles W. Luetje

Many insect behaviors are driven by olfaction, making insect olfactory receptors (ORs) appealing targets for insect control.  Insect ORs are odorant-gated ion channels, with each receptor thought to be composed of a representative from a large, variable family of odorant binding subunits and a highly conserved co-receptor subunit (Orco), assembled in an unknown stoichiometry.  Synthetic Orco directed agonists and antagonists have recently been identified.  Several Orco antagonists have been shown to act via an allosteric mechanism to inhibit OR activation by odorants.  The high degree of conservation of Orco across insect species results in Orco antagonists having broad activity at ORs from a variety of insect species and suggests that the binding site for Orco ligands may serve as a modulatory site for compounds endogenous to insects or may be a target of exogenous compounds, such as those produced by plants.  To test this idea, we screened a series of biogenic and trace amines, identifying several as Orco antagonists.  Of particular interest were tryptamine, a plant-produced amine, and tyramine, an amine endogenous to the insect nervous system.  Tryptamine was found to be a potent antagonist of Orco, able to block Orco activation by an Orco agonist and to allosterically inhibit activation of ORs by odorants.  Tyramine had effects similar to those of tryptamine, but was less potent.  Importantly, both tryptamine and tyramine displayed broad activity, inhibiting odorant activation of ORs of species from three different insect orders (Diptera, Lepidoptera and Coleoptera), as well as odorant activation of six diverse ORs from a single species (the human malaria vector mosquito, Anopheles gambiae).  Our results suggest that endogenous and exogenous natural compounds serve as Orco ligands modulating insect olfaction and that Orco can be an important target for the development of novel insect repellants.


2019 ◽  
Author(s):  
Shigenori Inagaki ◽  
Ryo Iwata ◽  
Masakazu Iwamoto ◽  
Takeshi Imai

SUMMARYSensory information is selectively or non-selectively inhibited and enhanced in the brain, but it remains unclear whether this occurs commonly at the peripheral stage. Here, we performed two-photon calcium imaging of mouse olfactory sensory neurons (OSNs) in vivo and found that odors produce not only excitatory but also inhibitory responses at their axon terminals. The inhibitory responses remained in mutant mice, in which all possible sources of presynaptic lateral inhibition were eliminated. Direct imaging of the olfactory epithelium revealed widespread inhibitory responses at OSN somata. The inhibition was in part due to inverse agonism toward the odorant receptor. We also found that responses to odor mixtures are often suppressed or enhanced in OSNs: Antagonism was dominant at higher odor concentrations, whereas synergy was more prominent at lower odor concentrations. Thus, odor responses are extensively tuned by inhibition, antagonism, and synergy, at the early peripheral stage, contributing to robust odor representations.


2021 ◽  
Vol 10 (16) ◽  
pp. 3554
Author(s):  
Dionysios J. Papachristou ◽  
Stavros Georgopoulos ◽  
Peter V. Giannoudis ◽  
Elias Panagiotopoulos

Fracture-healing is a complex multi-stage process that usually progresses flawlessly, resulting in restoration of bone architecture and function. Regrettably, however, a considerable number of fractures fail to heal, resulting in delayed unions or non-unions. This may significantly impact several aspects of a patient’s life. Not surprisingly, in the past few years, a substantial amount of research and number of clinical studies have been designed, aiming at shedding light into the cellular and molecular mechanisms that regulate fracture-healing. Herein, we present the current knowledge on the pathobiology of the fracture-healing process. In addition, the role of skeletal cells and the impact of marrow adipose tissue on bone repair is discussed. Unveiling the pathogenetic mechanisms that govern the fracture-healing process may lead to the development of novel, smarter, and more effective therapeutic strategies for the treatment of fractures, especially of those with large bone defects.


2020 ◽  
Author(s):  
Dr Siddhartha Sharma ◽  
Dr Anupam Mittal ◽  
Aditi Mahajan ◽  
Riddhi Gohil

Osteoclastogenesis (OCG) is a multi-stage process that involves formation of activated osteoclasts from bone marrow macrophages. The progression of each stage of OCG is governed by a set of transcription factors and gene regulators, which are genetically and epigenetically regulated at both transcription and post-transcription levels. Epigenetic changes are used to denote interactions between genetic material and environment leading to phenotypic alterations that can be inherited, without any variations in DNA sequence. Epigenetic and transcription regulatory events have profound effects on osteoclast formation and activation; these have been implicated in numerous disorders including osteoporosis, osteopetrosis, rheumatoid arthritis, spondyloarthritis, gout and bone metastasis. We aim to conduct a systematic review to assess possible relationship between key epigenetic and transcriptional regulators of osteoclastogenesis, and their role in specific bone disorders. This is a protocol for the proposed review. Keywords: osteoclasts; osteoclastogenesis; epigenetics; transcription; bone; skeletal disorders; methylation; histone proteins; micro RNA


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