Current Search: Department of Biological Sciences (x)
View All Items
Pages
- Title
- A feeling for the superorganism: expression of plant form in the lichen thallus.
- Creator
-
Sanders, William
- Abstract / Description
-
The composite thalli produced by lichen fungi in symbiosis with algae often show structural convergences with plants. Similar overall thallus forms and branching patterns may arise in lichens with very different anatomical construction, indicating the autonomy of the morphological level of organization. Fungal and algal growth and division may be highly integrated within meristem-like morphogenetic zones in many lichens, whereas in others the symbionts may contribute in a less synchronized...
Show moreThe composite thalli produced by lichen fungi in symbiosis with algae often show structural convergences with plants. Similar overall thallus forms and branching patterns may arise in lichens with very different anatomical construction, indicating the autonomy of the morphological level of organization. Fungal and algal growth and division may be highly integrated within meristem-like morphogenetic zones in many lichens, whereas in others the symbionts may contribute in a less synchronized fashion to the construction of the thallus. Although thallus-level morphology and morphogenesis may be compared with those of plants, ontogeny of the lichen thallus differs fundamentally. Observations of lichen ontogeny illustrate the formation of the thallus by unification of autonomous, primary cellular elements in co-ordinated growth. In land plants and many algae, by contrast, the plant body is the primary structure, the cellular elements of which represent secondary subdivisions. The convergences in form are based on a common mode of nutrition in combination with cell-wall building materials that impart similar structural potential. The photosynthetic apparatus forming the basis of this mode of nutrition is not a convergent feature, however, but a homologous structure that originated in the cyanobacteria and subsequently passed laterally into diverse biological lineages by repeated endosymbioses. With consolidation of these symbioses as eukaryotic algae and plants, the organismal level of organization was repeatedly re-established with increasing degrees of complexity, and morphological convergences were expressed at these new levels. In lichens, by contrast, the symbiosis is not organismally consolidated; morphological expression instead emerges at the superorganismal level.
Show less - Date Issued
- 2006-01-01
- Identifier
- fgcu_ir_000480
- Format
- Citation
- Title
- A new method for stranded whole transcriptome RNA-seq.
- Creator
-
Rhodes, Lyndsay, Miller, David F.B., Yan, Pearlly S., Buechlein, Aaron, Rodriguez, Benjamin A., Yilmaz, Ayse, Goel, Shokhi, Collins-Burow, Bridgette M., Braun, Chris, Pradeep,...
Show moreRhodes, Lyndsay, Miller, David F.B., Yan, Pearlly S., Buechlein, Aaron, Rodriguez, Benjamin A., Yilmaz, Ayse, Goel, Shokhi, Collins-Burow, Bridgette M., Braun, Chris, Pradeep, Sunila, Rupaimoole, Rajesha, Dalkilic, Mehmet, Sood, Anil K., Burow, Matthew E., Tang, Haixu, Huang, Tim H., Liu, Yunlong, Rusch, Douglas B., Nephew, Kenneth P.
Show less - Abstract / Description
-
This report describes an improved protocol to generate stranded, barcoded RNA-seq libraries to capture the whole transcriptome. By optimizing the use of duplex specific nuclease (DSN) to remove ribosomal RNA reads from stranded barcoded libraries, we demonstrate improved efficiency of multiplexed next generation sequencing (NGS). This approach detects expression profiles of all RNA types, including miRNA (microRNA), piRNA (Piwi-interacting RNA), snoRNA (small nucleolar RNA), lincRNA (long non...
Show moreThis report describes an improved protocol to generate stranded, barcoded RNA-seq libraries to capture the whole transcriptome. By optimizing the use of duplex specific nuclease (DSN) to remove ribosomal RNA reads from stranded barcoded libraries, we demonstrate improved efficiency of multiplexed next generation sequencing (NGS). This approach detects expression profiles of all RNA types, including miRNA (microRNA), piRNA (Piwi-interacting RNA), snoRNA (small nucleolar RNA), lincRNA (long non-coding RNA), mtRNA (mitochondrial RNA) and mRNA (messenger RNA) without the use of gel electrophoresis. The improved protocol generates high quality data that can be used to identify differential expression in known and novel coding and non-coding transcripts, splice variants, mitochondrial genes and SNPs (single nucleotide polymorphisms).
Show less - Date Issued
- 2013-04-01
- Identifier
- fgcu_ir_000441
- Format
- Citation
- Title
- Adult human mesenchymal stem cells enhance breast tumorigenesis and promote hormone independence.
- Creator
-
Rhodes, Lyndsay, Muir, Shannon E., Elliott, Steven, Guillot, Lori M., Antoon, James W., Penfornis, Patrice, Tilghman, Syreeta L., Salvo, Virgilo A., Fonseca, Juan P., Lacey,...
Show moreRhodes, Lyndsay, Muir, Shannon E., Elliott, Steven, Guillot, Lori M., Antoon, James W., Penfornis, Patrice, Tilghman, Syreeta L., Salvo, Virgilo A., Fonseca, Juan P., Lacey, Michelle R., Beckman, Barbara S., McLachlan, John A., Rowan, Brian G., Pochampally, Radhika, Burow, Matthew E.
Show less - Abstract / Description
-
Adult human mesenchymal stem cells (hMSCs) have been shown to home to sites of breast cancer and integrate into the tumor stroma. We demonstrate here the effect of hMSCs on primary breast tumor growth and the progression of these tumors to hormone independence. Co-injection of bone marrow-derived hMSCs enhances primary tumor growth of the estrogen receptor-positive, hormone-dependent breast carcinoma cell line MCF-7 in the presence or absence of estrogen in SCID/beige mice. We also show...
Show moreAdult human mesenchymal stem cells (hMSCs) have been shown to home to sites of breast cancer and integrate into the tumor stroma. We demonstrate here the effect of hMSCs on primary breast tumor growth and the progression of these tumors to hormone independence. Co-injection of bone marrow-derived hMSCs enhances primary tumor growth of the estrogen receptor-positive, hormone-dependent breast carcinoma cell line MCF-7 in the presence or absence of estrogen in SCID/beige mice. We also show hormone-independent growth of MCF-7 cells when co-injected with hMSCs. These effects were found in conjunction with increased immunohistochemical staining of the progesterone receptor in the MCF-7/hMSC tumors as compared to MCF-7 control tumors. This increase in PgR expression indicates a link between MCF-7 cells and MSCs through ER-mediated signaling. Taken together, our data reveal the relationship between tumor microenvironment and tumor growth and the progression to hormone independence. This tumor stroma-cell interaction may provide a novel target for the treatment of estrogen receptor-positive, hormone-independent, and endocrine-resistant breast carcinoma.
Show less - Date Issued
- 2009-07-12
- Identifier
- fgcu_ir_000457
- Format
- Citation
- Title
- AKT Regulation of Estrogen Receptor B Transcriptional Activity in Breast Cancer.
- Creator
-
Rhodes, Lyndsay, Duong, Bich N., Elliott, Steven, Frigo, Daniel E., Melnik, Lilia I., Tomchuck, Suzanne, Lebeau, Helena P., David, Odile, Beckman, Barbara S., Alam, Jawed,...
Show moreRhodes, Lyndsay, Duong, Bich N., Elliott, Steven, Frigo, Daniel E., Melnik, Lilia I., Tomchuck, Suzanne, Lebeau, Helena P., David, Odile, Beckman, Barbara S., Alam, Jawed, Bratton, Melyssa R., McLachlan, John A., Burow, Matthew E., author
Show less - Abstract / Description
-
Growth factor activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway has been shown to activate the estrogen receptor (ER) α and to mediate tamoxifen resistance in breast cancer. Here, we investigated the regulation of the transcriptional activity of the newer ERβ by PI3K-AKT signaling. Tissue arrays of breast cancer specimens showed a positive association between the expressions of AKT and ERβ in the clinical setting. Reporter gene assays using pharmacologic and molecular...
Show moreGrowth factor activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway has been shown to activate the estrogen receptor (ER) α and to mediate tamoxifen resistance in breast cancer. Here, we investigated the regulation of the transcriptional activity of the newer ERβ by PI3K-AKT signaling. Tissue arrays of breast cancer specimens showed a positive association between the expressions of AKT and ERβ in the clinical setting. Reporter gene assays using pharmacologic and molecular inhibitors of AKT and constitutively active AKT revealed for the first time the ability of AKT to (a) potentiate ERβ activity and (b) target predominantly the activation function-2 (AF2) domain of the receptor, with a requirement for residue K269. Given the importance of coactivators in ER transcriptional activity, we further investigated the possible involvement of steroid receptor coactivator 1 (SRC1) and glucocorticoid receptor-interacting protein 1 (GRIP1) in AKT regulation of ERβ. Mammalian two-hybrid assays revealed that AKT enhanced both SRC1 and GRIP1 recruitment to the ERβ-AF2 domain, and reporter gene analyses revealed that AKT and GRIP1 cooperatively potentiated ERβ-mediated transcription to a level much greater than either factor alone. Investigations into AKT regulation of GRIP with mammalian one-hybrid assays showed that AKT potentiated the activation domains of GRIP1 itself, and in vitro kinase assays revealed that AKT directly phosphorylated GRIP1. The cross-talk between the PI3K-AKT and ERβ pathways, as revealed by the ability of AKT to regulate several components of ERβ-mediated transcription, may represent an important aspect that may influence breast cancer response to endocrine therapy.
Show less - Date Issued
- 2006-09-01
- Identifier
- fgcu_ir_000461
- Format
- Citation
- Title
- Altered Death Receptor Signaling Promotes Epithelial-to-Mesenchymal Transition and Acquired Chemoresistance.
- Creator
-
Rhodes, Lyndsay, Antoon, James W., Lai, Rongye, Struckhoff, Amanda P., Nitzchke, Ashley M., Elliott, Steven, Martin, Elizabeth C., Yoon, Nam Seung, Salvo, Virgilo A., Shan, Bin,...
Show moreRhodes, Lyndsay, Antoon, James W., Lai, Rongye, Struckhoff, Amanda P., Nitzchke, Ashley M., Elliott, Steven, Martin, Elizabeth C., Yoon, Nam Seung, Salvo, Virgilo A., Shan, Bin, Beckman, Barbara S., Nephew, Kenneth P., Burow, Matthew E.
Show less - Abstract / Description
-
Altered death receptor signaling and resistance to subsequent apoptosis is an important clinical resistance mechanism. Here, we investigated the role of death receptor resistance in breast cancer progression. Resistance of the estrogen receptor alpha (ER)-positive, chemosensitive MCF7 breast cancer cell line to tumor necrosis factor (TNF) was associated with loss of ER expression and a multi-drug resistant phenotype. Changes in three major pathways were involved in this transition to a...
Show moreAltered death receptor signaling and resistance to subsequent apoptosis is an important clinical resistance mechanism. Here, we investigated the role of death receptor resistance in breast cancer progression. Resistance of the estrogen receptor alpha (ER)-positive, chemosensitive MCF7 breast cancer cell line to tumor necrosis factor (TNF) was associated with loss of ER expression and a multi-drug resistant phenotype. Changes in three major pathways were involved in this transition to a multidrug resistance phenotype: ER, Death Receptor and epithelial to mesenchymal transition (EMT). Resistant cells exhibited altered ER signaling, resulting in decreased ER target gene expression. The death receptor pathway was significantly altered, blocking extrinsic apoptosis and increasing NF-kappaB survival signaling. TNF resistance promoted EMT changes, resulting in a more aggressive phenotype. This first report identifying specific mechanisms underlying acquired resistance to TNF could lead to a better understanding of the progression of breast cancer in response to chemotherapy treatment.
Show less - Date Issued
- 2012-07-27
- Identifier
- fgcu_ir_000444
- Format
- Document (PDF)
- Title
- Amitriptyline versus Bupivacaine in Rat Sciatic Nerve Blockade.
- Creator
-
Mujtaba, Mustafa, Gerner, Peter, Sinnott, Catherine J., Kuo Wang, Ging
- Abstract / Description
-
TRICYCLIC antidepressants are commonly used orally in the therapy of chronic pain, such as diabetic neuropathy, 1,2 postherpetic neuralgia, 3 migraine, 4 fibromyalgia and myofascial pain, 5 chronic orofacial pain, 6 central pain, and peripheral neuropathy of different etiology. 7 Among them, amitriptyline has become a mainstay for the treatment of neuropathic pain, which is thought to be caused by an abnormal spontaneous high-frequency ectopic discharge. 8 Amitriptyline was shown to block...
Show moreTRICYCLIC antidepressants are commonly used orally in the therapy of chronic pain, such as diabetic neuropathy, 1,2 postherpetic neuralgia, 3 migraine, 4 fibromyalgia and myofascial pain, 5 chronic orofacial pain, 6 central pain, and peripheral neuropathy of different etiology. 7 Among them, amitriptyline has become a mainstay for the treatment of neuropathic pain, which is thought to be caused by an abnormal spontaneous high-frequency ectopic discharge. 8 Amitriptyline was shown to block various voltage-gated ion channels, for example, Na+, K+, and Ca+channels. 9–11 Furthermore, it inhibits the reuptake of serotonin and norepinephrine 12; blocks α2-adrenergic, nicotinic, muscarinic cholinergic, N -methyl-d-aspartate, and histaminergic receptors 13–17; and interacts with opioid and adenosine receptors. 18,19 Overall, the site of action of amitriptyline is probably both central and peripheral, 20 with a therapeutic plasma concentration of 0.3–0.8 μm. 21 One of the interesting features of amitriptyline is an additional Na+channel blockade (termed as use-dependent or phasic block) at high-frequency stimulation. For example, amitriptyline increased Na+channel blockade in isolated rabbit atrial and myocardial myocytes when stimulated at a high frequency 22; the same held true for voltage-gated Na+currents in bovine adrenal chromaffin cells and neonatal dorsal root ganglion cells. 9 This phenomenon of use dependency is also found with clinically used local anesthetics. Although in numerous reports amitriptyline was shown to effectively decrease the pain sensation, especially for thermal hyperalgesia in rats by various routes of administration (per oral, intrathecal, peritoneal), 23 or when combined with opioids or clonidine, 18,24 the exact mechanism of diminishing the pain sensation is not known. To date, amitriptyline has not been reported as a single agent for peripheral nerve blockade. We therefore compared the effectiveness of amitriptyline and bupivacaine for sciatic nerve blockade in rats. To extend our in vivo studies, we also extended former work on the potency and use-dependent blockade of amitriptyline 9 by investigating its voltage-dependent blockade and comparing it to bupivacaine during identical conditions in cultured neuronal cells.
Show less - Date Issued
- 2001-04-01
- Identifier
- fgcu_ir_000418
- Format
- Citation
- Title
- An activity to demonstrate the genetic code, gene duplication, and divergence.
- Creator
-
Demers, Nora
- Abstract / Description
-
Gene expression is a central tenant that is taught in introductory biology courses and many students seem to confuse the connection between transcription and translation, unaware of the wobble and redundancy of the genetic code. Furthermore, evolution is elegantly demonstrated by gene duplication and divergence. Here, Demers provides a way for students to practice using the genetic code and, as a result, to realize the redundancy of the genetic code by practicing reverse translation and...
Show moreGene expression is a central tenant that is taught in introductory biology courses and many students seem to confuse the connection between transcription and translation, unaware of the wobble and redundancy of the genetic code. Furthermore, evolution is elegantly demonstrated by gene duplication and divergence. Here, Demers provides a way for students to practice using the genetic code and, as a result, to realize the redundancy of the genetic code by practicing reverse translation and understand why it's physiologically impossible.
Show less - Date Issued
- 2011-07-01
- Identifier
- fgcu_ir_000398
- Format
- Citation
- Title
- An extensive characterization study of different Bacillus thuringiensis strains collected from the Nashville Tennessee area.
- Creator
-
Rolle, Roderick
- Abstract / Description
-
Bacillus thuringiensis (Bt) is a delta-endotoxins producing bacterium that inhibits the digestive process of many insect orders such as; lepidopteran, dipteran and coleopteran. A comparative study between sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis and DNA hybridization was performed on 25 chosen different strains of B. thuringiensis. Based on patterns from these molecular tools, the 25 isolates where grouped based on insect killing capability. Soil samples from Tennessee...
Show moreBacillus thuringiensis (Bt) is a delta-endotoxins producing bacterium that inhibits the digestive process of many insect orders such as; lepidopteran, dipteran and coleopteran. A comparative study between sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis and DNA hybridization was performed on 25 chosen different strains of B. thuringiensis. Based on patterns from these molecular tools, the 25 isolates where grouped based on insect killing capability. Soil samples from Tennessee were collected and analyzed for the presence of B. thuringiensis. Fifty six (56) of more than one hundred isolates collected were initially processed using the sodium acetate and a crystal protein staining procedure. Proteinaceous and genomic profiles were gathered for 25 isolates which were named Bt1 thru Bt25. DNA was extracted, quantified, amplified, cloned and sequenced. Alignment studies were performed on the sequenced products. This sequencing data helped decipher which of the Bt isolates belonged to the resembling parent category. The spore/crystal mixtures produced during sporulation were harvested by centrifugation at 10,000 g at 4°C. The spores and crystals were then separated using a discontinuous sucrose gradient with ultracentrifugation. The separation was confirmed by polarized microscopy. The crystal proteins were quantified and then separated using sodium dodecyl sulphate-polyacrylamide gel electrophresis (SDS-PAGE). A correlation was achieved between genomic and proteomic profiles which directly helped in grouping the 25 isolates. The compilation of data suggest that 14 of the 25 isolates resembled Bacillus thuringiensis subspecies kurstaki, four of the 25 isolates resembled B. thuringiensis subspecies israelensis while just one of the 25 isolates resembled B. thuringiensis subspecies tenebrionis. The overwhelming majority of the Bt isolates collected in our study resembled B. thuringiensis subspecies kurstaki. This can be due to the over use of genetically modified Bt corn in the late 1980’s which was subsequently dispersed into the environment.
Show less - Date Issued
- 2013-07-01
- Identifier
- fgcu_ir_000462
- Format
- Document (PDF)
- Title
- Antiestrogenic Effects of the Novel Sphingosine Kinase-2 Inhibitor ABC294640.
- Creator
-
Rhodes, Lyndsay, Antoon, James W., White, Martin D., Meacham, William D., Slaughter, Evelyn M., Muir, Shannon E., Elliott, Steven, Ashe, Hasina B., Wiese, Thomas E., Smith,...
Show moreRhodes, Lyndsay, Antoon, James W., White, Martin D., Meacham, William D., Slaughter, Evelyn M., Muir, Shannon E., Elliott, Steven, Ashe, Hasina B., Wiese, Thomas E., Smith, Charles D., Burow, Matthew E., Beckman, Barbara S.
Show less - Abstract / Description
-
Alterations in sphingolipid metabolism have been shown to contribute to the development of endocrine resistance and breast cancer tumor survival. Sphingosine kinase (SK), in particular, is overexpressed in breast cancer and is a promising target for breast cancer drug development. In this study, we used the novel SK inhibitor ABC294640 as a tool to explore the relationship between SK and estrogen (E2) receptor (ER) signaling in breast cancer cells. Treatment with ABC294640 decreased E2...
Show moreAlterations in sphingolipid metabolism have been shown to contribute to the development of endocrine resistance and breast cancer tumor survival. Sphingosine kinase (SK), in particular, is overexpressed in breast cancer and is a promising target for breast cancer drug development. In this study, we used the novel SK inhibitor ABC294640 as a tool to explore the relationship between SK and estrogen (E2) receptor (ER) signaling in breast cancer cells. Treatment with ABC294640 decreased E2-stimulated ERE-luciferase activity in both MCF-7 and ER-transfected HEK293 cells. Furthermore, the inhibitor reduced E2-mediated transcription of the ER-regulated genes progesterone receptor and SDF-1. Competitive receptor-binding assays revealed that ABC294640 binds in the antagonist ligand-binding domain of the ER, acting as a partial antagonist similar to tamoxifen. Finally, treatment with ABC294640 inhibited ER-positive breast cancer tumor formation in vivo. After 15 d of treatment with ABC294640, tumor volume was reduced by 68.4% (P < 0.05; n = 5) compared with control tumors, with no marked weight loss or illness. Taken together, these results provide strong evidence that this novel SK inhibitor, which had not previously been known to interact with E2 signaling pathways, has therapeutic potential in treating ER-positive breast cancer via inhibition of both SK and ER signaling.
Show less - Date Issued
- 2010-11-01
- Identifier
- fgcu_ir_000454
- Format
- Citation
- Title
- Argonaute 2 Expression Correlates with a Luminal B Breast Cancer Subtype and Induces Estrogen Receptor Alpha Isoform Variation.
- Creator
-
Rhodes, Lyndsay, Conger, Adrienne K., Martin, Elizabeth C., Yan, Thomas J., Hoang, Van T., La, Jacqueline, Anbalagan, Muralidharan, Burks, Hope E., Rowan, Brian G., Nephew,...
Show moreRhodes, Lyndsay, Conger, Adrienne K., Martin, Elizabeth C., Yan, Thomas J., Hoang, Van T., La, Jacqueline, Anbalagan, Muralidharan, Burks, Hope E., Rowan, Brian G., Nephew, Kenneth P., Collins-Burow, Bridgette M., Burow, Matthew E.
Show less - Abstract / Description
-
Estrogen receptor alpha (ERα) signaling pathways are frequently disrupted in breast cancer and contribute to disease progression. ERα signaling is multifaceted and many ERα regulators have been identified including transcription factors and growth factor pathways. More recently, microRNAs (miRNAs) are shown to deregulate ERα activity in breast carcinomas, with alterations in both ERα and miRNA expression correlating to cancer progression. In this study, we show that a high expression of...
Show moreEstrogen receptor alpha (ERα) signaling pathways are frequently disrupted in breast cancer and contribute to disease progression. ERα signaling is multifaceted and many ERα regulators have been identified including transcription factors and growth factor pathways. More recently, microRNAs (miRNAs) are shown to deregulate ERα activity in breast carcinomas, with alterations in both ERα and miRNA expression correlating to cancer progression. In this study, we show that a high expression of Argonaute 2 (AGO2), a translation regulatory protein and mediator of miRNA function, correlates with the luminal B breast cancer subtype. We further demonstrate that a high expression of AGO2 in ERα+ tumors correlates with a poor clinical outcome. MCF-7 breast cancer cells overexpressing AGO2 (MCF7-AGO2) altered ERα downstream signaling and selective ERα variant expression. Enhanced ERα-36, a 36 kDa ERα isoform, protein and gene expression was observed in vitro. Through quantitative polymerase chain reaction (qPCR), we demonstrate decreased basal expression of the full-length ERα and progesterone receptor genes, in addition to loss of estrogen stimulated gene expression in vitro. Despite the loss, MCF-7-AGO2 cells demonstrated increased estrogen stimulated tumorigenesis in vivo. Together with our clinical findings on AGO2 expression and the luminal B subtype, we suggest that AGO2 is a regulator of altered ERα signaling in breast tumors.
Show less - Date Issued
- 2016-09-01
- Identifier
- fgcu_ir_000431
- Format
- Document (PDF)
- Title
- Assessment of Differential Blockade by Amitriptyline and Its N -Methyl Derivative in Different Species by Different Routes.
- Creator
-
Mujtaba, Mustafa, Gerner, Peter, Haderer, Anna E., Sudoh, Yukari, Narang, Sanjeet, Abdi, Salahadin, Srinivasa, Venkatesh, Pertl, Christof, Kuo Wang, Ging
- Abstract / Description
-
In earlier work, amitriptyline was found to be a more potent local anesthetic than bupivacaine for rat sciatic nerve blockade, probably because of its greater potency to block Na+channels. 1,2 In that rat model, amitriptyline displayed some differential blocking properties, i.e. , selective block of specific (pain-transmitting) nerve fiber groups, 3 whereas no differential blockade was found with bupivacaine. This is in contradiction to the clinical impression that bupivacaine is the drug of...
Show moreIn earlier work, amitriptyline was found to be a more potent local anesthetic than bupivacaine for rat sciatic nerve blockade, probably because of its greater potency to block Na+channels. 1,2 In that rat model, amitriptyline displayed some differential blocking properties, i.e. , selective block of specific (pain-transmitting) nerve fiber groups, 3 whereas no differential blockade was found with bupivacaine. This is in contradiction to the clinical impression that bupivacaine is the drug of choice when a more sensory-selective action over motor blockade is desired. We hypothesize that species differences account for the different amounts of differential blockade seen previously. We therefore investigated the differential block phenomenon via two different routes of administration in two different species (peripheral sciatic nerve block in rats and intrathecal block in rats and sheep). In addition, because adding a methyl group to amitriptyline has been shown to increase blocking properties for K+channels in isolated rat sympathetic neurons, 4 we investigated whether this held true for Na+channels in GH3cells. We also investigated whether the addition of the methyl group to amitriptyline increased the amount of differential blockade. We studied this N -methyl derivative of amitriptyline because it has interesting physicochemical properties, i.e. , it is more soluble than amitriptyline and N -phenylethyl amitriptyline. 5 Preliminary electrophysiologic studies revealed that this drug is trapped within the cell and its block of sodium channels remains even after prolonged washoff.
Show less - Date Issued
- 2003-06-01
- Identifier
- fgcu_ir_000423
- Format
- Citation
- Title
- Bacteria, algae, and phycobionts: maintaining useful concepts and terminology.
- Creator
-
Sanders, William
- Abstract / Description
-
The assertion that the blue-greens (‘cyanobacteria’) are bacteria and not algae has led to alternative concepts for both of the latter terms. Bacteria is now often used to designate the prokaryote kingdom, that includes the blue-greens, while in other contexts it means specifically those prokaryotes that are not blue-greens. The term algae, on the other hand, has no biosystematic implications; it encompasses many phylogenetically independent lineages characterized by oxygen-evolving...
Show moreThe assertion that the blue-greens (‘cyanobacteria’) are bacteria and not algae has led to alternative concepts for both of the latter terms. Bacteria is now often used to designate the prokaryote kingdom, that includes the blue-greens, while in other contexts it means specifically those prokaryotes that are not blue-greens. The term algae, on the other hand, has no biosystematic implications; it encompasses many phylogenetically independent lineages characterized by oxygen-evolving photosynthesis. The algal status of the blue-greens is therefore not compromised by their classification among the bacteria. Current lichenological terminology, however, reflects the view that the blue-greens are not algae, thereby diverging from the concept of algae employed in phycology. The purpose and utility of terms that group organisms according to structural, functional and ecological criteria are insufficiently appreciated. These concepts do not compete with phylogenetic/ biosystematic classifications, but rather complement them.
Show less - Date Issued
- 2004-09-09
- Identifier
- fgcu_ir_000469
- Format
- Citation
- Title
- Both the Suppressor of Cytokine Signaling 1 (SOCS-1) Kinase Inhibitory Region and SOCS-1 Mimetic Bind to JAK2 Autophosphorylation Site: Implications for the Development of a SOCS-1 Antagonist.
- Creator
-
Mujtaba, Mustafa, Waiboci, Lilian W., Ahmed, Chulbul M., Flowers, Lawrence O., Martin, James P., Haider, Mohammed I., Johnson, Howard M.
- Abstract / Description
-
Suppressor of cytokine signaling (SOCS)-1 protein modulates signaling by IFN-γ by binding to the autophosphorylation site of JAK2 and by targeting bound JAK2 to the proteosome for degradation. We have developed a small tyrosine kinase inhibitor peptide (Tkip) that is a SOCS-1 mimetic. Tkip is compared in this study with the kinase inhibitory region (KIR) of SOCS-1 for JAK2 recognition, inhibition of kinase activity, and regulation of IFN-γ-induced biological activity. Tkip and a peptide...
Show moreSuppressor of cytokine signaling (SOCS)-1 protein modulates signaling by IFN-γ by binding to the autophosphorylation site of JAK2 and by targeting bound JAK2 to the proteosome for degradation. We have developed a small tyrosine kinase inhibitor peptide (Tkip) that is a SOCS-1 mimetic. Tkip is compared in this study with the kinase inhibitory region (KIR) of SOCS-1 for JAK2 recognition, inhibition of kinase activity, and regulation of IFN-γ-induced biological activity. Tkip and a peptide corresponding to the KIR of SOCS-1, (53)DTHFRTFRSHSDYRRI(68) (SOCS1-KIR), both bound similarly to the autophosphorylation site of JAK2, JAK2(1001–1013). The peptides also bound to JAK2 peptide phosphorylated at Tyr1007, pJAK2(1001–1013). Dose-response competitions suggest that Tkip and SOCS1-KIR similarly recognize the autophosphorylation site of JAK2, but probably not precisely the same way. Although Tkip inhibited JAK2 autophosphorylation as well as IFN-γ-induced STAT1-α phosphorylation, SOCS1-KIR, like SOCS-1, did not inhibit JAK2 autophosphorylation but inhibited STAT1-α activation. Both Tkip and SOCS1-KIR inhibited IFN-γ activation of Raw 264.7 murine macrophages and inhibited Ag-specific splenocyte proliferation. The fact that SOCS1-KIR binds to pJAK2(1001–1013) suggests that the JAK2 peptide could function as an antagonist of SOCS-1. Thus, pJAK2(1001–1013) enhanced suboptimal IFN-γ activity, blocked SOCS-1-induced inhibition of STAT3 phosphorylation in IL-6-treated cells, enhanced IFN-γ activation site promoter activity, and enhanced Ag-specific proliferation. Furthermore, SOCS-1 competed with SOCS1-KIR for pJAK2(1001–1013). Thus, the KIR region of SOCS-1 binds directly to the autophosphorylation site of JAK2 and a peptide corresponding to this site can function as an antagonist of SOCS-1.
Show less - Date Issued
- 2007-04-15
- Identifier
- fgcu_ir_000427
- Format
- Citation
- Title
- Characterization of a Peptide Inhibitor of Janus Kinase 2 That Mimics Suppressor of Cytokine Signaling 1 Function.
- Creator
-
Mujtaba, Mustafa, Flowers, Lawrence O., Johnson, Howard M., Ellis, Morgan R., Haider, S. Mohammed I., Subramaniam, Prem S.
- Abstract / Description
-
Positive and negative regulation of cytokines such as IFN-γ are key to normal homeostatic function. Negative regulation of IFN-γ in cells occurs via proteins called suppressors of cytokine signaling (SOCS)1 and -3. SOCS-1 inhibits IFN-γ function by binding to the autophosphorylation site of the tyrosine kinase Janus kinase (JAK)2. We have developed a short 12-mer peptide, WLVFFVIFYFFR, that binds to the autophosphorylation site of JAK2, resulting in inhibition of its autophosphorylation as...
Show morePositive and negative regulation of cytokines such as IFN-γ are key to normal homeostatic function. Negative regulation of IFN-γ in cells occurs via proteins called suppressors of cytokine signaling (SOCS)1 and -3. SOCS-1 inhibits IFN-γ function by binding to the autophosphorylation site of the tyrosine kinase Janus kinase (JAK)2. We have developed a short 12-mer peptide, WLVFFVIFYFFR, that binds to the autophosphorylation site of JAK2, resulting in inhibition of its autophosphorylation as well as its phosphorylation of IFN-γ receptor subunit IFNGR-1. The JAK2 tyrosine kinase inhibitor peptide (Tkip) did not bind to or inhibit tyrosine autophosphorylation of vascular endothelial growth factor receptor or phosphorylation of a substrate peptide by the protooncogene tyrosine kinase c-src. Tkip also inhibited epidermal growth factor receptor autophosphorylation, consistent with the fact that epidermal growth factor receptor is regulated by SOCS-1 and SOCS-3, similar to JAK2. Although Tkip binds to unphosphorylated JAK2 autophosphorylation site peptide, it binds significantly better to tyrosine-1007 phosphorylated JAK2 autophosphorylation site peptide. SOCS-1 only recognizes the JAK2 site in its phosphorylated state. Thus, Tkip recognizes the JAK2 autophosphorylation site similar to SOCS-1, but not precisely the same way. Consistent with inhibition of JAK2, Tkip inhibited the ability of IFN-γ to induce an antiviral state as well as up-regulate MHC class I molecules on cells at a concentration of ∼10 μM. This is similar to the Kd of SOCS-3 for the erythropoietin receptor. These data represent a proof-of-concept demonstration of a peptide mimetic of SOCS-1 that regulates JAK2 tyrosine kinase function.
Show less - Date Issued
- 2004-06-15
- Identifier
- fgcu_ir_000425
- Format
- Citation
- Title
- Collaboration for point-of-need library instruction.
- Creator
-
Demers, Nora, Malenfant, Chuck
- Abstract / Description
-
Beginning in the spring of 2001, a librarian and a member of the teaching faculty collaborated on an advanced information literacy instructional experience through the teaching faculty's "Issues in Science and Technology" classes. They collected data from the students both before and after the advanced information literacy instructional sessions that included the students' own attitudes about, and perceived level of, information literacy. Additionally, the instructor assigned point values to...
Show moreBeginning in the spring of 2001, a librarian and a member of the teaching faculty collaborated on an advanced information literacy instructional experience through the teaching faculty's "Issues in Science and Technology" classes. They collected data from the students both before and after the advanced information literacy instructional sessions that included the students' own attitudes about, and perceived level of, information literacy. Additionally, the instructor assigned point values to assignments directly related to the information literacy instruction her students received, thereby encouraging participation. The collaborators found that increasing the point values of the related assignments also increased student participation and performance. They also found strong indications that offering advanced library instruction to upper-division students at their point of need, as they are facing more challenging research assignments in their regular coursework, also increases student interest and participation in the program.
Show less - Date Issued
- 2004-01-01
- Identifier
- fgcu_ir_000401, 10.1108/00907320410553678
- Format
- Citation
- Title
- Combustion and Energy Transfer Experiments.
- Creator
-
Brown, David, Dubetz, Terry, Schmidt, Diane L., Gillman, Edward, Alberte, Randall, Egiebor, Nosa O., Beatty, Thomas, Isern, Sharon, Barreto, Jose
- Abstract / Description
-
Core concepts can be integrated throughout lower-division science and engineering courses by using a series of related, cross-referenced laboratory experiments. Starting with butane combustion in chemistry, we expanded the underlying core concepts of energy transfer into laboratories designed for biology, physics, and engineering.
- Date Issued
- 2007-01-01
- Identifier
- fgcu_ir_000494
- Format
- Citation
- Title
- Complete life cycle of the lichen fungus Calopadia puiggarii (Pilocarpaceae, Ascomycetes) documented in situ: Propagule dispersal, establishment of symbiosis, thallus development, and formation of sexual and asexual reproductive structures.
- Creator
-
Sanders, William
- Abstract / Description
-
The life histories of lichen fungi are not well known and cannot be readily studied in laboratory culture. This work documents in situ the complete life cycle of the widespread crustose lichen Calopadia puiggarii, which reproduces sexually and asexually on the surfaces of leaves.
- Date Issued
- 2014-11-01
- Identifier
- fgcu_ir_000474
- Format
- Citation
- Title
- Cytokine Receptor CXCR4 Mediates Estrogen-Independent Tumorigenesis, Metastasis, and Resistance to EndocrineTherapy in Human Breast Cancer.
- Creator
-
Rhodes, Lyndsay, Short, Sarah P., Neel, Nicole F., Salvo, Virgilo A., Zhu, Yun, Elliott, Steven, Yu, Dihua, Sun, Menghong, Muir, Shannon E., Fonseca, Juan P., Bratton, Melyssa R...
Show moreRhodes, Lyndsay, Short, Sarah P., Neel, Nicole F., Salvo, Virgilo A., Zhu, Yun, Elliott, Steven, Yu, Dihua, Sun, Menghong, Muir, Shannon E., Fonseca, Juan P., Bratton, Melyssa R., Segar, Chris, Tilghman, Syreeta L., Sobolik-Delmaire, Tammy, Horton, Linda W., Zaja-Milatovic, Snjezana, Collins-Burow, Bridgette M., Wadsworth, Scott, Beckman, Barbara S.
Show less - Abstract / Description
-
Estrogen independence and progression to a metastatic phenotype are hallmarks of therapeutic resistance and mortality in breast cancer patients. Metastasis has been associated with chemokine signaling through the SDF-1–CXCR4 axis. Thus, the development of estrogen independence and endocrine therapy resistance in breast cancer patients may be driven by SDF-1–CXCR4 signaling. Here we report that CXCR4 overexpression is indeed correlated with worse prognosis and decreased patient survival...
Show moreEstrogen independence and progression to a metastatic phenotype are hallmarks of therapeutic resistance and mortality in breast cancer patients. Metastasis has been associated with chemokine signaling through the SDF-1–CXCR4 axis. Thus, the development of estrogen independence and endocrine therapy resistance in breast cancer patients may be driven by SDF-1–CXCR4 signaling. Here we report that CXCR4 overexpression is indeed correlated with worse prognosis and decreased patient survival irrespective of the status of the estrogen receptor (ER). Constitutive activation of CXCR4 in poorly metastatic MCF-7 cells led to enhanced tumor growth and metastases that could be reversed by CXCR4 inhibition. CXCR4 overexpression in MCF-7 cells promoted estrogen independence in vivo, whereas exogenous SDF-1 treatment negated the inhibitory effects of treatment with the anti-estrogen ICI 182,780 on CXCR4-mediated tumor growth. The effects of CXCR4 overexpression were correlated with SDF-1–mediated activation of downstream signaling via ERK1/2 and p38 MAPK (mitogen activated protein kinase) and with an enhancement of ER-mediated gene expression. Together, these results show that enhanced CXCR4 signaling is sufficient to drive ER-positive breast cancers to a metastatic and endocrine therapy-resistant phenotype via increased MAPK signaling. Our findings highlight CXCR4 signaling as a rational therapeutic target for the treatment of ER-positive, estrogen-independent breast carcinomas needing improved clinical management.
Show less - Date Issued
- 2011-01-01
- Identifier
- fgcu_ir_000452
- Format
- Citation
- Title
- Dengue virus antibodies enhance Zika virus infection.
- Creator
-
Paul, Lauren M, Carlin, Eric R, Jenkins, Meagan M, Tan, Amanda L, Barcellona, Carolyn M, Nicholson, Cindo O, Michael, Scott F, Isern, Sharon
- Abstract / Description
-
For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted...
Show moreFor decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction. DENV and ZIKV are closely related, resulting in substantial antigenic overlap. Through antibody-dependent enhancement (ADE), anti-DENV antibodies can enhance the infectivity of DENV for certain classes of immune cells, causing increased viral production that correlates with severe disease outcomes. Similarly, ZIKV has been shown to undergo ADE in response to antibodies generated by other flaviviruses. We tested the neutralizing and enhancing potential of well-characterized broadly neutralizing human anti-DENV monoclonal antibodies (HMAbs) and human DENV immune sera against ZIKV using neutralization and ADE assays. We show that anti-DENV HMAbs, cross-react, do not neutralize, and greatly enhance ZIKV infection in vitro. DENV immune sera had varying degrees of neutralization against ZIKV and similarly enhanced ZIKV infection. Our results suggest that pre-existing DENV immunity may enhance ZIKV infection in vivo and may lead to increased disease severity. Understanding the interplay between ZIKV and DENV will be critical in informing public health responses and will be particularly valuable for ZIKV and DENV vaccine design and implementation strategies.
Show less - Date Issued
- 2016-12-16
- Identifier
- 10.1038/cti.2016.72, fgcu_ir_000083, http://doi.wiley.com/10.1038/cti.2016.72
- Format
- Citation
- Title
- Design and probing of efflux functions of EGFP fused ABC membrane transporters in live cells using fluorescence spectroscopy.
- Creator
-
Lee, Kerry, Ding, Feng, Vahedi-Faridi, Ardeschir, Huang, Tao, Xu, X. Nancy
- Abstract / Description
-
We have designed and constructed fusion genes of C-terminal (Ct) or N-terminal (Nt) bmrA with EGFP vectors and successfully expressed them in ΔBmrA (BmrA deletion strain of Bacillus subtilis), generating two new strains of B. subtilis (Ct-BmrA-EGFP and Nt-BmrA-EGFP). The fusion genes were characterized using gel electrophoresis and DNA sequencing. Their expression in live cells was determined by measuring the fluorescence of EGFP in single live cells using fluorescence microscopy and...
Show moreWe have designed and constructed fusion genes of C-terminal (Ct) or N-terminal (Nt) bmrA with EGFP vectors and successfully expressed them in ΔBmrA (BmrA deletion strain of Bacillus subtilis), generating two new strains of B. subtilis (Ct-BmrA-EGFP and Nt-BmrA-EGFP). The fusion genes were characterized using gel electrophoresis and DNA sequencing. Their expression in live cells was determined by measuring the fluorescence of EGFP in single live cells using fluorescence microscopy and spectroscopy. The efflux function of the new strains was studied by measuring their accumulation kinetics of intracellular Hoechst dye molecules (a pump substrate) using fluorescence spectroscopy, which were compared with wild-type (WT-BmrA) and ΔBmrA strains. Both new strains show lower accumulation rates than ΔBmrA, and their efflux kinetics are inhibited by a pump inhibitor (orthovanadate). The results suggest that both strains extrude the dye molecules and the fusion proteins retain the efflux function of BmrA (ATP-binding cassette, ABC, transporter). Notably, Nt-BmrA-EGFP strain shows lower accumulation rates (higher efflux rates) than Ct-BmrA-EGFP. Modeled structures of the fusion proteins illustrate a highly flexible linker region connecting EGFP with BmrA, suggesting a minimal obstruction of EGFP to the BmrA. A closer distance of two C termini (∼14 Å) than two N termini (47.9 Å) of the 'closed' BmrA dimer depicts the larger steric effect of C-terminal fusion. This study also shows that glucose affects the fluorescence study of efflux function of BmrA, suggesting that efflux kinetics of ABC membrane transporters in live cells must be characterized in the absence of glucose.
Show less - Date Issued
- 2011-06-01
- Identifier
- fgcu_ir_000411
- Format
- Citation