The novel tumor suppressor NOL7 post-transcriptionally regulates thrombospondin-1 expression.
Creator:
Zhou, G., Doci, Colleen L., and Lingen, M.W.
Related Url Tesim:
https://pubmed.ncbi.nlm.nih.gov/23085760/ and https://www.nature.com/articles/onc2012464
Description:
Thrombospondin-1 (TSP-1) is an endogenous inhibitor of angiogenesis whose expression suppresses tumor growth in vivo. Like many angiogenesis-related genes, TSP-1 expression is tightly controlled by various mechanisms, but there is little data regarding the contribution of post-transcriptional processing to this regulation. NOL7 is a novel tumor suppressor that induces an antiangiogenic phenotype and suppresses tumor growth, in part through upregulation of TSP-1. Here we demonstrate that NOL7 is an mRNA-binding protein that must localize to the nucleoplasm to exert its antiangiogenic and tumor suppressive effects. There, it associates with the RNA-processing machinery and specifically interacts with TSP-1 mRNA through its 3'UTR. Reintroduction of NOL7 into SiHa cells increases luciferase expression through interaction with the TSP-1 3'UTR at both the mRNA and protein levels. NOL7 also increases endogenous TSP-1 mRNA half-life. Further, NOL7 post-transcriptional stabilization is observed in a subset of angiogenesis-related mRNAs, suggesting that the stabilization of TSP-1 may be part of a larger novel mechanism. These data demonstrate that NOL7 significantly alters TSP-1 expression and may be a master regulator that coordinates the post-transcriptional expression of key signaling factors critical for the regulation of the angiogenic phenotype.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
License Tesim:
http://creativecommons.org/licenses/by-sa/3.0/us/
Language:
English
Publisher:
Nature Publishing Group
Identifier:
PMID: 23085760, 10.1038/onc.2012.464, and PMCID: PMC6698137
Online discussions in biochemistry to increase peer interactions and student interest
Creator:
Wilson, Kristy J.
Related Url Tesim:
Available from the publisher website: https://iubmb.onlinelibrary.wiley.com/doi/10.1002/bmb.21487 and Available for access or request from the library catalog: https://marianunivindianapolis.on.worldcat.org/oclc/45409187
Description:
Abstract
The online environment poses a number of challenges, including creating
opportunities for students to interact and get to know each other. I propose
adding online discussions that can allow students to explore the real-world
implications of biochemistry to provide course context, build the classroom community,
diversify student assessment, and practice communication and information
literacy skills. Utilizing current events and elements of students' daily lives
can help students interconnect what they are learning and increase student
interest in the course. These discussions ask students to explore a topic, reflect
on what they would like to learn, find information, and report back on what
they have learned. Herein I provide an example of a discussion prompt, a table
of other potential discussion topics that are aligned with common biochemistry
course topics, and results from student survey supporting discussion format.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
Publisher:
International Union of Biochemistry and Molecular Biology
Identifier:
DOI: 10.1002/bmb.21487
Type:
Article
Keyword:
malnutrition, interest, discussion, and biochemistry
Date Created:
Revised: 21 October 2020, Accepted: 8 December 2020, and Received: 31 August 2020
The Phloem-Resident Protein OCTOPUS is a Novel Regulator of flg22-induced Responses in Arabidopsis thaliana
Creator:
Stegemann, Katherine A., Collins, Carina, Melena, I., King, C., and Greenwood, K.
Related Url Tesim:
Preprint DOI: https://doi.org/10.1101/2022.01.27.478095, Supplementary Material: https://www.biorxiv.org/content/10.1101/2022.01.27.478095v1.supplementary-material, Available from the library catalog: https://marianunivindianapolis.on.worldcat.org/oclc/9398554509, and Available from the publisher: https://www.biorxiv.org/content/10.1101/2022.01.27.478095v1
Description:
Phloem is a critical tissue that transports photosynthates and extracellular signals in vascular plants. Although a functional phloem is necessary for plant health, it is also an ideal environment for pathogens to access host nutrients to promote pathogenesis. Even though many vascular pathogens induce economically relevant crop damage, very little is known about the mechanism(s) by which phloem cells detect potential pathogens and signal to minimize damage. Our lab searched existing phosphoproteomic databases, mining for proteins that were phosphorylated in response to the defense-elicitor flagellin, or flg22, AND were expressed in vascular cells, and we identified Octopus (OPS). OPS is polarly associated with the plasma membrane (PM) of sieve element cells and promotes their differentiation from procambial precursor cells by inhibiting the function of BIN2 in brassinosteroid-related signaling. The observation that OPS is differentially phosphorylated in response to flg22 led us to the examine whether OPS may function in flg22-induced signaling using Arabidopsis T-DNA insertion mutants lacking a functional OPS. In wild-type (WT) seedlings, flg22 binds to the PM receptor flagellin sensing 2 (FLS2) to initiate three branches of a signaling cascade that culminates in increased expression of distinct marker genes. Ultimately these signaling pathways lead to the restriction of pathogen growth. Two independent alleles of ops were treated with 100 μM flg22 and marker genes from all three branches of FLS2 signaling exhibited higher expression than WT. We also found that in the absence of any flg22, ops mutants displayed increased flg22 signaling responses. Our results indicate that OPS may function as a negative regulator of flg22-induced signaling events and is one of very few phloem-resident proteins with a documented role in flg22 signaling. These results indicate that the phloem may be able to sense and response to the threat of bacterial pathogens in a unique way. Competing Interest Statement The authors have declared no competing interest.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
Language:
English
Publisher:
Cold Spring Harbor Laboratory Press
Identifier:
DOI: https://doi.org/10.1101/2022.01.27.478095
Type:
Article
Keyword:
Arabidopsis, phloem, FLS2, plant immunity, gene expression, and BRI1
Recommendations for an inclusive undergraduate plant science classroom
Creator:
Butler, K. J. , Collins, Carina A. , and Robison, J. D.
Related Url Tesim:
Available from the publisher website: https://doi.org/10.1093/plcell/koab167 and Available for access or request from the library catalog: https://marianunivindianapolis.on.worldcat.org/oclc/43431395
Description:
We argue that one of the best ways to improve equity and diversity in the plant sciences begins in the undergraduate
classroom. Our classrooms are the first stop for the next generation of plant scientists, and we must engage students with inclusive and anti-racist STEM pedagogy. In this letter, we will discuss the importance of utilizing evidence-based inclusive teaching practices, as well as providing short- and long-term ways each of us can implement them in our classrooms.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
Publisher:
American Society of Plant Biologists
Identifier:
doi:10.1093/plcell/koab167
Type:
Article
Keyword:
plant science, undergraduate education, pedagogy, biology, and inclusivity
Research Across the Curriculum Rubric (RAC-R): An Adaptable Rubric for the Evaluation of Journal Article Style Lab Reports
Alternative title:
Trends in Teaching Experimentation in the Life Sciences : Putting Research into Practice to Drive Institutional Change
Creator:
Wilson, Kristy J. and Kinkade, Karla B.
Related Url Tesim:
Available from the library catalog at: https://marianunivindianapolis.on.worldcat.org/oclc/1320814472 and Available from the publisher at: https://link.springer.com/chapter/10.1007/978-3-030-98592-9_15#citeas
Description:
Practitioners of course-based undergraduate research experiences (CUREs) often evaluate student learning through journal article style lab reports. In our biology department, CUREs are used in multiple required and elective course labs to teach biology students how real scientific experimentation is conducted. We utilize journal article style lab reports to assess student learning since scientific writing is an important currency for scientists. Faculty have found that student writing does not always improve as students’ progress toward graduation and that we find ourselves teaching fundamentals of scientific writing to advanced students that should have been mastered earlier in their academic careers. Furthermore, biology students fail to grasp that even though the biological sub-discipline is different, the skills and content associated with the writing are similar. To address these concerns, we have developed a Research Across the Curriculum Rubric (RAC-R) for assessing student scientific writing. Herein, we present our rubric as well as the process and timeline we used for its development, the intra-departmental communication required to ensure that the rubric would meet the needs of multiple instructors across several biology disciplines, and examples of how we have adapted the rubric for use in both upper and lower-level courses.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
Language:
English
Publisher:
Springer Nature
Identifier:
ISBN: 978-3-030-98591-2 and ISBN: 978-3-030-98592-9
Type:
Part of Book
Keyword:
Rubric, Assessment, Scientific writing, Information literacy, Course mapping, Lab reports, and Course-based undergraduate research experience (CURE)
Scientific Process Flowchart Assessment (SPFA): A Method for Evaluating Changes in Understanding and Visualization of the Scientific Process in a Multidisciplinary Student Population
Creator:
Wilson, Kristy J. and Rigakos, Bessie
Related Url Tesim:
https://www.lifescied.org/doi/full/10.1187/cbe.15-10-0212 and https://pubmed.ncbi.nlm.nih.gov/27856551/
Description:
The scientific process is nonlinear, unpredictable, and ongoing. Assessing the nature of science is difficult with methods that rely on Likert-scale or multiple-choice questions. This study evaluated conceptions about the scientific process using student-created visual representations that we term "flowcharts." The methodology, Scientific Process Flowchart Assessment (SPFA), consisted of a prompt and rubric that was designed to assess students' understanding of the scientific process. Forty flowcharts representing a multidisciplinary group without intervention and 26 flowcharts representing pre- and postinstruction were evaluated over five dimensions: connections, experimental design, reasons for doing science, nature of science, and interconnectivity. Pre to post flowcharts showed a statistically significant improvement in the number of items and ratings for the dimensions. Comparison of the terms used and connections between terms on student flowcharts revealed an enhanced and more nuanced understanding of the scientific process, especially in the areas of application to society and communication within the scientific community. We propose that SPFA can be used in a variety of circumstances, including in the determination of what curricula or interventions would be useful in a course or program, in the assessment of curriculum, or in the evaluation of students performing research projects.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
Language:
English
Publisher:
American Society for Cell Biology
Identifier:
PMCID: PMC5132360, 10.1187/cbe.15-10-0212, and PMID: 27856551
SDF-1/CXCL12 induces directional cell migration and spontaneous metastasis via a CXCR4/Gαi/mTORC1 axis.
Creator:
Mikelis, Constantinos M., Zárate-Bladés, Carlos Rodrigo, Leelahavanichkul, Kantima, Wang, Zhiyong, Martin, Daniel, Doci, Colleen L., Dorsam, Robert T., Amornphimoltham, Panomwat, Gutkind, J. Silvio, Patel, Vyomesh, Weigert, Roberto, Masedunskas, Andrius, Molinolo, Alfredo A., and Dillenburg-Pilla, Patricia
Related Url Tesim:
https://pubmed.ncbi.nlm.nih.gov/25466898/ and https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.14-260083
Description:
Multiple human malignancies rely on C-X-C motif chemokine receptor type 4 (CXCR4) and its ligand, SDF-1/CXCL12 (stroma cell-derived factor 1/C-X-C motif chemokine 12), to metastasize. CXCR4 inhibitors promote the mobilization of bone marrow stem cells, limiting their clinical application for metastasis prevention. We investigated the CXCR4-initiated signaling circuitry to identify new potential therapeutic targets. We used HeLa human cancer cells expressing high levels of CXCR4 endogenously. We found that CXCL12 promotes their migration in Boyden chamber assays and single cell tracking. CXCL12 activated mTOR (mechanistic target of rapamycin) potently in a pertussis-sensitive fashion. Inhibition of mTOR complex 1 (mTORC1) by rapamycin [drug concentration causing 50% inhibition (IC50) = 5 nM] and mTORC1/mTORC2 by Torin2 (IC50 = 6 nM), or by knocking down key mTORC1/2 components, Raptor and Rictor, respectively, decreased directional cell migration toward CXCL12. We developed a CXCR4-mediated spontaneous metastasis model by implanting HeLa cells in the tongue of SCID-NOD mice, in which 80% of the animals develop lymph node metastasis. It is surprising that mTORC1 disruption by Raptor knockdown was sufficient to reduce tumor growth by 60% and spontaneous metastasis by 72%, which were nearly abolished by rapamycin. In contrast, disrupting mTORC2 had no effect in tumor growth or metastasis compared with control short hairpin RNAs. These data suggest that mTORC1 may represent a suitable therapeutic target in human malignancies using CXCR4 for their metastatic spread. .
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
Language:
English
Publisher:
Federation of American Societies for Experimental Biology (FASEB)
Identifier:
10.1096/fj.14-260083, PMID: 25466898, and PMCID: PMC4422355
Type:
Article
Keyword:
rapamycin., lymphangiogenesis, chemotaxis, mTOR, and cancer
SEMA3F is an antilymphangiogenic signaling molecule expressed in the proliferating basal layer of normal epithelium. In orthotopic models of head and neck squamous cell carcinoma, loss of SEMA3F or its receptors results in enhanced tumor growth and locoregional metastasis, leading to speculation that SEMA3F may also prevent cancer initiation. To determine whether the loss of SEMA3F enhances susceptibility to cancer development, we employed a two‐step carcinogenesis model in a robustly immunogenic outbred strain of wild‐type (WT) or Sema3F knockout (KO) mice. Animals were treated with a single application of 7,12‐Dimethylbenz(a)anthracene (DMBA) followed by twice‐weekly applications of 12‐O‐Tetradecanoylphorbol‐13‐acetate (TPA) for 24 weeks. Sema3F KO animals had a modest but statistical decrease in tumor latency compared with WT. Additionally, both the number and size of lesions was significantly decreased in KO animals. Together, this suggested that loss of Sema3F may be influencing cancer development and progression primarily through modulation of the tumor microenvironment. By histochemical staining, KO animals demonstrated much higher percentage of immune infiltrate within the tumors. To investigate whether immunosurveillance may contribute to the diminished cancer progression in KO animals, we analyzed the mRNA expression of inflammatory cytokines from these animals. Analysis of the inflammatory tumor microenvironment in these lesions revealed a strong induction of both IL‐12α and IL‐1β in KO animals. Primarily produced by macrophages, IL‐12α has been shown to suppress the development of skin papillomas and suppress tumor growth and development. Compellingly, macrophages but not leukocytes express Sema3F receptors. Consequently, we propose that expression of Sema3F in the context of chemical carcinogenesis functions as a macrophage chemorepellent and antilymphangiogenic molecule, thus delaying the onset of an adaptive immune response and increasing the latency and tumor burden. Further, Sema3F may be an attractive target for cancer immunotherapies given its autocrine and paracrine signaling roles.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
Language:
English
Identifier:
10.1096/fasebj.2020.34.s1.00629
Type:
Article
Keyword:
tumor initiation, cancer immunotherapies, Sema3F, and antilymphangiogenic signaling molecule
Semaphorin signaling in angiogenesis, lymphangiogenesis and cancer.
Creator:
Doci, Colleen L., Gutkind, J. Silvio, and Sakurai, Atsuko
Related Url Tesim:
Originally published in Cell Research: https://www.nature.com/articles/cr2011198 and https://pubmed.ncbi.nlm.nih.gov/22157652/
Description:
Angiogenesis, the formation of new blood vessels from preexisting vasculature, is essential for many physiological processes, and aberrant angiogenesis contributes to some of the most prevalent human diseases, including cancer. Angiogenesis is controlled by delicate balance between pro- and anti-angiogenic signals. While pro-angiogenic signaling has been extensively investigated, how developmentally regulated, naturally occurring anti-angiogenic molecules prevent the excessive growth of vascular and lymphatic vessels is still poorly understood. In this review, we summarize the current knowledge on how semaphorins and their receptors, plexins and neuropilins, control normal and pathological angiogenesis, with an emphasis on semaphorin-regulated anti-angiogenic signaling circuitries in vascular and lymphatic endothelial cells. This emerging body of information may afford the opportunity to develop novel anti-angiogenic therapeutic strategies.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
License Tesim:
http://creativecommons.org/licenses/by-nc/3.0/us/
Language:
English
Publisher:
Nature Publishing Group
Identifier:
PMID: 22157652, 10.1038/cr.2011.198, and PMCID: PMC3351930
Type:
Article
Keyword:
Physiologic, Neuropilins, Signal Transduction, Semaphorins, Endothelial Cells, Animals, Nerve Tissue Proteins, Pathologic, Neoplasms, Neovascularization, Lymphangiogenesis, Cell Adhesion Molecules, and Humans