Slack R.J.,Fibrosis and Lung Injury Discovery Performance Unit |
Hafeji M.,Fibrosis and Lung Injury Discovery Performance Unit |
Rogers R.,Fibrosis and Lung Injury Discovery Performance Unit |
Ludbrook S.B.,Biological science |
And 4 more authors.
Pharmacology | Year: 2016
A20FMDV2 is a peptide derived from the foot-and-mouth disease virus with a high affinity and selectivity for the alpha-v beta-6 (αvβ6) arginyl-glycinyl-aspartic acid (RGD)-binding integrin. It has been shown to be an informative tool ligand in pre-clinical imaging studies for selective labelling of the αvβ6 integrin in a number of disease models. In a radioligand binding assay using a radiolabelled form of the peptide ([3H]A20FMDV2), its high affinity (KD: 0.22 nmol/l) and selectivity (at least 85-fold) for αvβ6 over the other members of the RGD integrin family was confirmed. [3H]A20FMDV2 αvβ6 binding could be fully reversed only in the presence of EDTA, whereas a partial reversal was observed in the presence of excess concentrations of an RGD-mimetic small molecule (SC-68448) or unlabelled A20FMDV2. Using flow cytometry on bronchial epithelial cells, the ligand-induced internalization of αvβ6 by A20FMDV2 and latency-associated peptide-1 was shown to be fast (t1/2: 1.5 and 3.1 min, respectively), concentration-dependent (EC50: values 1.1 and 3.6 nmol/l, respectively) and was followed by a moderately slow return of integrin to the surface. The results of the radioligand binding studies suggest that the binding of A20FMDV2 to the RGD-binding site on αvβ6 is required to maintain its engagement with the hypothesised A20FMDV2 synergy site on the integrin. In addition, there is evidence from flow cytometric studies that the RGD-ligand engagement of αvβ6 post-internalization plays a role in delaying recycling of the integrin to the cell surface. This mechanism may act as a homeostatic control of membrane αvβ6 following RGD ligand engagement. © 2016 S. Karger AG, Basel.
Rathnayake S.S.,Biological science |
Frederick H.,Chemistry and Biochemistry |
Arhar T.,Loyola Marymount University |
Cocklin S.,Drexel University |
Kooijman E.E.,Biological science
Journal of Lipid Research | Year: 2016
Lipid droplets (LDs) are organelles that contribute to various cellular functions that are vital for life. Aside from acting as a neutral lipid storage depot, they are also involved in building new membranes, synthesis of steroid hormones, and cell signaling. Many aspects of LD structure and function are not yet well-understood. Here we investigate the interaction of perilipin 3, a member of the perilipin family of LD binding proteins, and three N-terminal truncation mutants with lipid monolayers. The interaction is studied as a function of surface pressure for a series of systematically chosen lipids. We find that the C terminus of perilipin 3 has different insertion behavior from that of the longer truncation mutants and the full-length protein. Inclusion of N-terminal sequences with the C terminus decreases the ability of the protein construct to insert in lipid monolayers. Coupling of anionic lipids to negative spontaneous curvature facilitates protein interaction and insertion. The C terminus shows strong preference for lipids with more saturated fatty acids. This work sheds light on the LD binding properties and function of the different domains of perilipin 3.-Mirheydari, M., S. S. Rathnayake, H. Frederick, T. Arhar, E. K. Mann, S. Cocklin, and E. E. Kooijman. Insertion of perilipin 3 into a glycero(phospho)lipid monolayer depends on lipid headgroup and acyl chain species. J. Lipid Res. 2016. 57: 1465-1476. © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.
PubMed | University of Pittsburgh, Human Genetics and., Vanderbilt University, Tennessee Valley Authority and Biological science
Type: Journal Article | Journal: Journal of the American Society of Nephrology : JASN | Year: 2016
Retinoic acid (RA) has been used therapeutically to reduce injury and fibrosis in models of AKI, but little is known about the regulation of this pathway and what role it has in regulating injury and repair after AKI. In these studies, we show that RA signaling is activated in mouse and zebrafish models of AKI, and that these responses limit the extent of injury and promote normal repair. These effects were mediated through a novel mechanism by which RA signaling coordinated the dynamic equilibrium of inflammatory M1 spectrum versus alternatively activated M2 spectrum macrophages. Our data suggest that locally synthesized RA represses proinflammatory macrophages, thereby reducing macrophage-dependent injury post-AKI, and activates RA signaling in injured tubular epithelium, which in turn promotes alternatively activated M2 spectrum macrophages. Because RA signaling has an essential role in kidney development but is repressed in the adult, these findings provide evidence of an embryonic signaling pathway that is reactivated after AKI and involved in reducing injury and enhancing repair.
Vandhana S.,Vision Research Foundation |
Deepa P.R.,Pilani Chennai Center |
Aparna G.,Biological science |
Jayanthi U.,Vision Research Foundation |
Krishnakumar S.,Vision Research Foundation
Indian Journal of Biochemistry and Biophysics | Year: 2010
Triclosan, a broad spectrum antibiotic is currently being evaluated for its anti-cancer property. Though several solvents are available to dissolve lipophilic (hydrophobic) drugs, solubility and toxicity aspects pose a challenge, when combined with the cell culture medium. In this paper, we present a simple approach based on physico-chemical and biologic criteria to choose a suitable solubilizing agent to study the anti-proliferative property of triclosan in breast cancer cell line MCF-7. Triclosan was dissolved in five different solvents viz. DMSO, absolute ethanol, 1 N NaOH, 55% polyethylene glycol + 45% ethanol mixture (PEM) and acetone and diluted with the culture medium (1 mg/ml). Although triclosan dissolved completely in all five solvents, on dilution with culture medium, turbidity was observed in DMSO, 1 N NaOH and ethanol. Cell viability was 95.23% in 10 μl of acetone, when compared with 49.45% at the same volume of PEM. This non-toxic nature of acetone was supported by DNA fragmentation analysis and phase contrast microscopy. A significant decrease in cancer cell proliferation at 100 μg/ml of acetone-solubilized triclosan, compared with 100 μg/ml of PEM-solubilized triclosan (p<0.05) indicated stronger anti-proliferative effect and greater drug-sensitivity of triclosan when solubilized in acetone. Results showed that acetone-solubilized triclosan was suitable for anti-cancer investigations in cultured MCF-7 cells.
PubMed | Lovely Professional University, Presidency University of India and Biological science
Type: | Journal: Biotechnology advances | Year: 2017
Alzheimers disease (AD) is a severe, chronic and progressive neurodegenerative disease associated with memory and cognition impairment ultimately leading to death. It is the commonest reason of dementia in elderly populations mostly affecting beyond the age of 65. The pathogenesis is indicated by accumulation of the amyloid-beta (A) plaques and neurofibrillary tangles (NFT) in brain tissues and hyperphosphorylation of tau protein in neurons. The main cause is considered to be the formation of reactive oxygen species (ROS) due to oxidative stress. The current treatment provides only symptomatic relief by offering temporary palliative therapy which declines the rate of cognitive impairment associated with AD. Inhibition of the enzyme acetylcholinesterase (AChE) is considered as one of the major therapeutic strategies offering only symptomatic relief and moderate disease-modifying effect. Other non-cholinergic therapeutic approaches include antioxidant and vitamin therapy, stem cell therapy, hormonal therapy, use of antihypertensive or lipid-lowering medications and selective phosphodiesterase (PDE) inhibitors, inhibition of -secretase and -secretase and A aggregation, inhibition of tau hyperphosphorylation and intracellular NFT, use of nonsteroidal anti-inflammatory drugs (NSAIDs), transition metal chelators, insulin resistance drugs, etanercept, brain-derived neurotrophic factor (BDNF) etc. Medicinal plants have been reported for possible anti-AD activity in a number of preclinical and clinical trials. Ethnobotany, being popular in China and in the Far East and possibly less emphasized in Europe, plays a substantial role in the discovery of anti-AD agents from botanicals. Chinese Material Medica (CMM) involving Chinese medicinal plants has been used traditionally in China in the treatment of AD. Ayurveda has already provided numerous lead compounds in drug discovery and many of these are also undergoing clinical investigations. A number of medicinal plants either in their crude forms or as isolated compounds have exhibited to reduce the pathological features associated with AD. In this present review, an attempt has been made to elucidate the molecular mode of action of various plant extracts, phytochemicals and traditional herbal formulations investigated against AD as reported in various preclinical and clinical tests. Herbal synergism often found in polyherbal formulations were found effective to combat disease heterogeneity as found in complex pathogenesis of AD. Finally a note has been added to describe biotechnological improvement, genetic and genomic resources and mathematical and statistical techniques for empirical model building associated with anti-AD plant secondary metabolites and their source botanicals.
Parrott B.B.,University of Georgia |
Chiang Y.,Harvard University |
Hudson A.,University of Georgia |
Sarkar A.,Biological Science |
And 2 more authors.
PLoS ONE | Year: 2011
Production of specialized cells from precursors depends on a tightly regulated sequence of proliferation and differentiation steps. In the gonad of Drosophila melanogaster, the daughters of germ line stem cells (GSC) go through precisely four rounds of transit amplification divisions to produce clusters of 16 interconnected germ line cells before entering a stereotypic differentiation cascade. Here we show that animals harbouring a transposon insertion in the center of the complex nucleoporin98-96 (nup98-96) locus had severe defects in the early steps of this developmental program, ultimately leading to germ cell loss and sterility. A phenotypic analysis indicated that flies carrying the transposon insertion, designated nup98-962288, had dramatically reduced numbers of germ line cells. In contrast to controls, mutant testes contained many solitary germ line cells that had committed to differentiation as well as abnormally small clusters of two, four or eight differentiating germ line cells. This indicates that mutant GSCs rather differentiated than self-renewed, and that these GSCs and their daughters initiated the differentiation cascade after zero, or less than four rounds of amplification divisions. This phenotype remained unaffected by hyper-activation of signalling pathways that normally result in excessive proliferation of GSCs and their daughters. Expression of wildtype nup98-96 specifically in the germ line cells of mutant animals fully restored development of the GSC lineage, demonstrating that the effect of the mutation is cell-autonomous. Nucleoporins are the structural components of the nucleopore and have also been implicated in transcriptional regulation of specific target genes. The nuclear envelopes of germ cells and general nucleocytoplasmic transport in nup98-96 mutant animals appeared normal, leading us to propose that Drosophila nup98-96 mediates the transport or transcription of targets required for the developmental timing between amplification and differentiation. © 2011 Parrott et al.
Rios A.C.,University of California at San Diego |
French G.,Biological science
Journal of Chemical Education | Year: 2011
Chemical education occurs in settings other than just the chemistry classroom. High school biology courses are frequently where students are introduced to organic molecules and their importance to cellular chemistry. However, structural representations are often intimidating because students have not been introduced to the language. As part of a National Science Foundation (NSF) GK-12 program, we designed and implemented a classroom activity to help students become familiar with the symbolic nature of bond-line structures and to gain experience in recognizing distinctive features among classes of organic molecules.Odorant molecules associated with food are engaging vehicles for students to make structural observations and practice pattern recognition for the discovery of functional groups; they also learn the rules for unwritten carbon and hydrogen atoms. Introducing the molecular nature of odors and the associated smells provides a tangible chemistry-biology connection that stimulates students' interests in organic chemistry while learning the structural language used by practicing chemists. © 2011 American Chemical Society and Division of Chemical Education, Inc.
Wyatt H.J.,Biological science
Vision Research | Year: 2010
Video-based devices for measuring gaze direction are widespread. However, there is a built-in imprecision in such devices in the event that pupil diameter changes during the experiments. Data are presented to demonstrate this effect. The possibility of correcting eye-position records for the imprecision is discussed and preliminary examples of such correction are presented. © 2010 Elsevier Ltd.
Wreh E.,Biological science
11AIChE - 2011 AIChE Spring Meeting and 7th Global Congress on Process Safety, Conference Proceedings | Year: 2011
Cattails are a potential source of biomass for the production of cellulosic ethanol. The efficiency of sulfuric acid and ammonia pretreatment methods in preparing cattail biomass for ethanol production were compared. Dried, powdered cattail leaves were pretreated either by autoclaving them with 2% sulfuric acid for 1 hr or by incubating them overnight at 40°C in 15% aqueous ammonia. Samples of the dried, pretreated solid were treated with cellulase and glucosidase for 48 hr. To compare the efficiency of the pretreatment methods, glucose liberated in the samples was measured using a glucose oxidase assay. Overall, 27.8% of the starting biomass was recovered as glucose with ammonia pretreatment compared to 11.7% for sulfuric acid pretreatment. In addition, 22.3% of the starting biomass was recovered as glucose when no pretreatment was used. This is an abstract of a paper presented at the 2011 AIChE Spring Meeting & 7th Global Congress on Process Safety (Chicago, IL 3/13-17/2011).
Hewitt G.M.,Biological science
Genetica | Year: 2011
The older history of hybrid zones is explored through consideration of recent advances in climatology, paleontology and phylogeography in the Late Cenozoic, particularly the Quaternary Period with its major climatic cycles. The fossil record shows that these ice ages and their nested millennial oscillations caused substantial changes in species distributions and with genetic evidence allows deduction of refugia and colonization routes in arctic, temperate, desert and tropical regions. The age of divergence between hybridizing lineages varies from the Late Pleistocene to the Late Miocene, implying much range change and varying selection on sister lineages. Hybridizing lineages in the Tropical and Temperate regions range in age from young to old, but those studied in the Arctic are no more than a few ice ages old and their refugial roots are not clear. Mid to low latitude regions often show parapatric patchworks of lineages and multiple refugia stable through many climatic oscillations. Particular hybrid zones may have formed more than once; while some expansions were not the same, producing reticulation and introgression in previous glacial cycles. Hybrid-zone roots are complex and deep, and considerations of their complexity can reveal evolutionary pathways of species. They are indeed windows on evolution. © 2011 Springer Science+Business Media B.V.