AIMS Molecular Science最新文献

{"title":"Influence of heat shock proteins in individual sensitivity of human neutrophils to heat stress","authors":"V. Semenkov, A. Mikhalskii, A. Sapoznikov","doi":"10.3934/MOLSCI.2019.2.38","DOIUrl":"https://doi.org/10.3934/MOLSCI.2019.2.38","url":null,"abstract":"We have developed a simple and reliable method to measure the sensitivity of individuals to oxidative stress. This method utilizes luminol-amplified chemiluminescence to quantify production of reactive oxygen species (ROS) by opsonized zymosan-stimulated neutrophils that have been subjected to short-term stress via heat shock. In this study, the chemiluminescence reaction was used to monitor the dynamics of ROS production in neutrophils derived from 17 patients of different ages and genders before and after these neutrophils were subjected to heat shock. In addition, we determined expression of Toll-like receptors using fluorescent-labeled antibody. The effects of adrenaline, dexamethasone, aspirin, and indomethacin, as well as different doses of exogenous heat shock protein 70 (Hsp70), on the production of ROS by stimulated neutrophils was also investigated. Our data showed that adrenaline and exogenous Hsp70 both suppressed ROS production by stimulated neutrophils. Furthermore, TLR4 expression was upregulated upon heat stress. Thus, adrenaline, HSPs, and TLRs may all play a role in regulating stress responses in phagocytes.","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2019-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43286038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocannabinoid system involvement in autism spectrum disorder: An overview with potential therapeutic applications","authors":"S. Schultz, D. Siniscalco","doi":"10.3934/MOLSCI.2019.1.27","DOIUrl":"https://doi.org/10.3934/MOLSCI.2019.1.27","url":null,"abstract":"Persistent deficits in social communication, restricted-repetitive patterns of behavior, interests, or activities are the core domains characterizing autism spectrum disorder (ASD). In this spectrum are grouped a heterogeneous and complex set of neurodevelopmental conditions. ASD shows pro-inflammatory events and immune system dysfunction. The endocannabinoid (EC) system is an intricate molecular network of lipid signaling pathways. The building-blocks are the arachidonic acid-derived compounds (anandamide, AEA) and 2-arachidonoyl glycerol (2-AG), their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2), and their associated biosynthesizing and degradating enzymes. Recent evidence highlights a strong involvement of the EC system in the pathophysiology of some neuropsychiatric disorders and of ASD. Indeed, the EC system is able to regulate several metabolic and cellular pathways involved in autism, especially regulation of the immune system. ASD-related changes in the immune system involve alterations in monocyte and macrophage responses and pro-inflammatory cytokine up-regulation. It has been demonstrated that these processes are driven by EC system dysfunction, opening the way for targeting this system with novel drugs for ASD. Potentially, pharmacologic treatment with cannabidiol (CBD) is expected to increase endocannabinoid tone by increasing anandamide levels. Additionally, evidence from the literature indicates that CBD may alleviate many conditions co-occurring with ASD, such as seizures, gastro-intestinal problems, anxiety and depression, attention deficit, and sleep problems.","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2019-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42574236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autism, 75 years of history: From psychoanalysis to neurobiology","authors":"A. Parisi, S. Parisi","doi":"10.3934/MOLSCI.2019.1.20","DOIUrl":"https://doi.org/10.3934/MOLSCI.2019.1.20","url":null,"abstract":"In this article we evaluated the lengthy seventy-five year history of Autism Spectrum Disorder beginning with the first diagnosis in 1943 and the first etiological orientations (psychodynamic factors) until today, in which the approach to behavioral problems has increasingly become neurobiological in nature. Abnormal relationships, verbal communication impairments and stereotyped behaviors, are no longer considered the cause of the problem, but rather the manifestation of this problem. Additionally, these factors must not be considered a “problem” and should be viewed as an “adaptation”. In other words, a way through which individuals with different anatomical and functional nervous system give “meanings” to their own bodies and the external world. Subjects with autism have a different connectome. Their neuronal network, under life experiences (learning), has undergone an abnormal selection. In modern words, talking about connectome, could mean direct our attention and studies on the body-brain relationship and chronic inflammation.","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2019-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70225265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phospholipid—the dynamic structure between living and non-living world; a much obligatory supramolecule for present and future","authors":"M. Alagumuthu, Divakar Dahiya, P. Nigam","doi":"10.3934/MOLSCI.2019.1.1","DOIUrl":"https://doi.org/10.3934/MOLSCI.2019.1.1","url":null,"abstract":"Phospholipids (PLs) are amphiphilic molecules that are in charge of controlling what goes in or out of the cell, keeping up the structure and numerous associated functions. These primary molecules are not only the integral part but also a vastly diverse group of molecules present in microorganisms, plants, and animals. PLs provide rigidity, signal transduction, energy to cells. PLs such as lecithins are molecules of future food, medicine and cosmetic industry. PLs are used in fat and oil refining and these are also used as carriers in drug and drug delivery system. Of course, challenges are there in the assay of phospholipids because of their availability of hydrophobic and hydrophilic components in the same environment. This review is mainly focused to unveil the function, characteristics, features and applications of PLs in various fields.","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2019-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47333377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expedited isolation of natural product peptidyl-tRNA hydrolase inhibitors from a Pth1 affinity column.","authors":"Harkirat S Sethi,&nbsp;Jessica L Osier,&nbsp;Geordan L Burks,&nbsp;Jennifer F Lamar,&nbsp;Hana McFeeters,&nbsp;Robert L McFeeters","doi":"10.3934/molsci.2017.2.175","DOIUrl":"https://doi.org/10.3934/molsci.2017.2.175","url":null,"abstract":"<p><p>New antibiotics and new antibiotic targets are needed to counter the development of bacterial drug resistance that threatens to return the human population to the pre-antibiotic era. Bacterial peptidyl-tRNA hydrolase (Pth1) is a promising new antibiotic target in the early stages of development. While inhibitory activity has been observed in a variety of natural products, bioactive fractionation has been a bottleneck for inhibitor isolation. To expedite the isolation of inhibitory compounds from complex mixtures, we constructed a Pth1 affinity column and used it to isolate inhibitory compounds from crude natural products. Recombinantly produced <i>S. typhimurium</i> Pth1 was covalently attached to a column matrix and the inhibitory activity isolated from ethanol extracts of <i>Salvinia minima</i>. The procedure reported here demonstrates that isolation of Pth1 inhibitory compounds from complex natural product extracts can be greatly expedited over traditional bioactive fractionation, decreasing time and expense. The approach is generally applicable to Pth1s from other bacterial species and opens an avenue to advance and accelerate inhibitor development against this promising antimicrobial target.</p>","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36936233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triclosan antimicrobial polymers.","authors":"Richard C Petersen","doi":"10.3934/molsci.2016.1.88","DOIUrl":"https://doi.org/10.3934/molsci.2016.1.88","url":null,"abstract":"<p><p>Triclosan antimicrobial molecular fluctuating energies of nonbonding electron pairs for the oxygen atom by ether bond rotations are reviewed with conformational computational chemistry analyses. Subsequent understanding of triclosan alternating ether bond rotations is able to help explain several material properties in Polymer Science. Unique bond rotation entanglements between triclosan and the polymer chains increase both the mechanical properties of polymer toughness and strength that are enhanced even better through secondary bonding relationships. Further, polymer blend compatibilization is considered due to similar molecular relationships and polarities. With compatibilization of triclosan in polymers a more uniform stability for nonpolar triclosan in the polymer solid state is retained by the antimicrobial for extremely low release with minimum solubility into aqueous solution. As a result, triclosan is projected for long extended lifetimes as an antimicrobial polymer additive. Further, triclosan rapid alternating ether bond rotations disrupt secondary bonding between chain monomers in the resin state to reduce viscosity and enhance polymer blending. Thus, triclosan is considered for a polymer additive with multiple properties to be an antimicrobial with additional benefits as a nonpolar toughening agent and a hydrophobic wetting agent. The triclosan material relationships with alternating ether bond rotations are described through a complete different form of medium by comparisons with known antimicrobial properties that upset bacterial cell membranes through rapid fluctuating mechanomolecular energies. Also, triclosan bond entanglements with secondary bonding can produce structural defects in weak bacterial lipid membranes requiring pliability that can then interfere with cell division. Regarding applications with polymers, triclosan can be incorporated by mixing into a resin system before cure, melt mixed with thermoplastic polymers that set on cooling into a solid or alternatively applied as a coating through several different methods with dissolving into an organic solvent and dried on by evaporation as a common means.</p>","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3934/molsci.2016.1.88","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34453267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress, innate immunity, and age-related macular degeneration.","authors":"Peter X Shaw,&nbsp;Travis Stiles,&nbsp;Christopher Douglas,&nbsp;Daisy Ho,&nbsp;Wei Fan,&nbsp;Hongjun Du,&nbsp;Xu Xiao","doi":"10.3934/molsci.2016.2.196","DOIUrl":"https://doi.org/10.3934/molsci.2016.2.196","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer's disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have previously hypothesized that the tight homeostatic control of inflammation via the innate immune system is likely critical for avoidance of disease progression. However, the presence of a multitude of potential triggers of inflammation results in a sensitive balance in which perturbations thereof would subsequently alter the inflammatory state of the retina, leading to a state of chronic inflammation and pathologic progression. In this review, we will highlight the background literature surrounding the known genetic and environmental contributors to AMD risk, as well as a discussion of the potential mechanistic interplay of these factors that lead to disease pathogenesis with particular emphasis on the delicate control of inflammatory homeostasis and the centrality of the innate immune system in this process.</p>","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34529984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mitotic checkpoint complex (MCC): looking back and forth after 15 years.","authors":"Song-Tao Liu,&nbsp;Hang Zhang","doi":"10.3934/molsci.2016.4.597","DOIUrl":"https://doi.org/10.3934/molsci.2016.4.597","url":null,"abstract":"<p><p>The mitotic checkpoint is a specialized signal transduction pathway that contributes to the fidelity of chromosome segregation. The signaling of the checkpoint originates from defective kinetochore-microtubule interactions and leads to formation of the mitotic checkpoint complex (MCC), a highly potent inhibitor of the Anaphase Promoting Complex/Cyclosome (APC/C)-the E3 ubiquitin ligase essential for anaphase onset. Many important questions concerning the MCC and its interaction with APC/C have been intensively investigated and debated in the past 15 years, such as the exact composition of the MCC, how it is assembled during a cell cycle, how it inhibits APC/C, and how the MCC is disassembled to allow APC/C activation. These efforts have culminated in recently reported structure models for human MCC:APC/C supra-complexes at near-atomic resolution that shed light on multiple aspects of the mitotic checkpoint mechanisms. However, confusing statements regarding the MCC are still scattered in the literature, making it difficult for students and scientists alike to obtain a clear picture of MCC composition, structure, function and dynamics. This review will comb through some of the most popular concepts or misconceptions about the MCC, discuss our current understandings, present a synthesized model on regulation of CDC20 ubiquitination, and suggest a few future endeavors and cautions for next phase of MCC research.</p>","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35521242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amyloid misfolding, aggregation, and the early onset of protein deposition diseases: insights from AFM experiments and computational analyses","authors":"Y. Lyubchenko","doi":"10.3934/molsci.2015.3.190","DOIUrl":"https://doi.org/10.3934/molsci.2015.3.190","url":null,"abstract":"The development of Alzheimer’s disease is believed to be caused by the assembly of amyloid β proteins into aggregates and the formation of extracellular senile plaques. Similar models suggest that structural misfolding and aggregation of proteins are associated with the early onset of diseases such as Parkinson’s, Huntington’s, and other protein deposition diseases. Initially, the aggregates were structurally characterized by traditional techniques such as x-ray crystallography, NMR, electron microscopy, and AFM. However, data regarding the structures formed during the early stages of the aggregation process were unknown. Experimental models of protein deposition diseases have demonstrated that the small oligomeric species have significant neurotoxicity. This highlights the urgent need to discover the properties of these species, to enable the development of efficient diagnostic and therapeutic strategies. The oligomers exist transiently, making it impossible to use traditional structural techniques to study their characteristics. The recent implementation of single-molecule imaging and probing techniques that are capable of probing transient states have enabled the properties of these oligomers to be characterized. Additionally, powerful computational techniques capable of structurally analyzing oligomers at the atomic level advanced our understanding of the amyloid aggregation problem. This review outlines the progress in AFM experimental studies and computational analyses with a primary focus on understanding the very first stage of the aggregation process. Experimental approaches can aid in the development of novel sensitive diagnostic and preventive strategies for protein deposition diseases, and several examples of these approaches will be discussed.","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2015-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3934/molsci.2015.3.190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70225194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theory of partial agonist activity of steroid hormones.","authors":"Carson C Chow,&nbsp;Karen M Ong,&nbsp;Benjamin Kagan,&nbsp;S Stoney Simons","doi":"10.3934/molsci.2015.2.101#sthash.jxRCteJz.dpuf","DOIUrl":"https://doi.org/10.3934/molsci.2015.2.101#sthash.jxRCteJz.dpuf","url":null,"abstract":"<p><p>The different amounts of residual partial agonist activity (PAA) of antisteroids under assorted conditions have long been useful in clinical applications but remain largely unexplained. Not only does a given antagonist often afford unequal induction for multiple genes in the same cell but also the activity of the same antisteroid with the same gene changes with variations in concentration of numerous cofactors. Using glucocorticoid receptors as a model system, we have recently succeeded in constructing from first principles a theory that accurately describes how cofactors can modulate the ability of agonist steroids to regulate both gene induction and gene repression. We now extend this framework to the actions of antisteroids in gene induction. The theory shows why changes in PAA cannot be explained simply by differences in ligand affinity for receptor and requires action at a second step or site in the overall sequence of reactions. The theory also provides a method for locating the position of this second site, relative to a concentration limited step (CLS), which is a previously identified step in glucocorticoid-regulated transactivation that always occurs at the same position in the overall sequence of events of gene induction. Finally, the theory predicts that classes of antagonist ligands may be grouped on the basis of their maximal PAA with excess added cofactor and that the members of each class differ by how they act at the same step in the overall gene induction process. Thus, this theory now makes it possible to predict how different cofactors modulate antisteroid PAA, which should be invaluable in developing more selective antagonists.</p>","PeriodicalId":44217,"journal":{"name":"AIMS Molecular Science","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33312347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}