ABT-510 is an effective chemopreventive agent in the mouse 4-nitroquinoline 1-oxide model of oral carcinogenesis.
Creator:
Martin, Leslie E., Jones, Colleen L., Hasina, Rifat, Jalil, Asif, Lingen, Mark W., and Kasza, Kristen
Related Url Tesim:
https://cancerpreventionresearch.aacrjournals.org/content/2/4/385.long and https://pubmed.ncbi.nlm.nih.gov/19336725/
Description:
Despite numerous advances, the 5-year survival rate for head and neck squamous cell cancer (HNSCC) has remained largely unchanged. This poor outcome is due to several variables, including the development of multiple primary tumors. Therefore, it is essential to supplement early detection with preventive strategies. Using the 4-nitroquinoline 1-oxide (4-NQO) mouse model, we sought to define an appropriate dose and duration of administration that would predict the histologic timeline of HNSCC progression. Additionally, we sought to determine the timing of the onset of the angiogenic phenotype. Finally, using ABT-510 as a proof-of-principle drug, we tested the hypothesis that inhibitors of angiogenesis can slow/delay the development of HNSCC. We determined that 8 weeks of 100 microg/mL 4-NQO in the drinking water was the optimal dosage and duration to cause a sufficient incidence of hyperkeratoses, dysplasias, and HNSCC over a period of 32 weeks with minimal morbidity and mortality. Increased microvessel density and vascular endothelial growth factor expression in hyperkeratotic lesions provided evidence that the initiation of the angiogenic phenotype occurred before the development of dysplasia. Importantly, ABT-510 significantly decreased the overall incidence of HNSCC from 37.3% to 20.3% (P = 0.021) as well as the combined incidence of dysplasia and HNSCC from 82.7% to 50.6% (P < 0.001). These findings suggest that our refinement of the 4-NQO model allows for the investigation of the histologic, molecular, and biological alterations that occur during the premalignant phase of HNSCC. In addition, these data support the hypothesis that inhibitors of angiogenesis may be promising chemopreventive agents. and Colleen L Jones (Doci) not affiliated with Marian University-Indianapolis at time of publication.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
Language:
English
Identifier:
PMID: 19336725, PMCID: PMC2702843, and 10.1158/1940-6207.CAPR-08-0211
Castor canadensis Kuhl (North American beavers) are central place foragers who<br />collect woody plants and building materials from their surroundings and return to a main body of water containing a lodge or food cache. It has been suggested that beavers dredge water-filled canals to extend access to foraging areas; however, the possibility that these engineered transportation routes function as extensions to the beavers' "central place" has yet to be considered. Our objective in this study was to gain a better understanding of the formation and utilization of canals by beavers and thus further elucidate the complex foraging behavior of these ecosystem engineers. During 2004–2011, we mapped beaver ponds, canals, and cut stumps in eight groundwater-fed wetlands, from at least four separate colonies, in Indianapolis, IN. We found that the mean length, depth, and width of the beaver-dredged canals were 604.3 6 493.1 m, 28.0 6 22.2 cm, and 107.7 6 107.1 cm respectively. Two of the canal systems were mapped for multiple years and their length, depth, and width increased over time and supported the prediction that beavers continuously "engineer" these canal systems to extend their foraging area into new locations. In addition, and in contrast to previous studies, we found that the number of beaver-cut stumps was negatively related to distance from canals, but not from the body of water containing their lodges. We recommend that studies of optimal foraging in beavers take canals into account, where applicable, when relating foraging to distance from the "central place."
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
Language:
English
Publisher:
Indiana Academy of Science
Type:
Article
Keyword:
foraging, North American beaver, canal, and Castor canadensis
Characterization of NOL7 gene point mutations, promoter methylation, and protein expression in cervical cancer.
Creator:
Doci, Colleen L., Langerman, Alexander, Kanteti, Rajani, Lingen,Mark W., Ostler, Kelly R., Onel,Kenan, Godley, Lucy A., Mankame, Tanmayi P., Best, Timothy, and Salgia, Ravi
Related Url Tesim:
Originally publiched in the International Journal of Gynecological Pathology here: https://journals.lww.com/intjgynpathology/Fulltext/2012/01000/Characterization_of_NOL7_Gene_Point_Mutations,.3.aspx and https://pubmed.ncbi.nlm.nih.gov/22123719/
Description:
NOL7 is a putative tumor suppressor gene localized to 6p23, a region with frequent loss of heterozygosity in a number of cancers, including cervical cancer (CC). We have previously demonstrated that reintroduction of NOL7 into CC cells altered the angiogenic phenotype and suppressed tumor growth in vivo by 95%. Therefore, to understand its mechanism of inactivation in CC, we investigated the genetic and epigenetic regulation of NOL7. NOL7 mRNA and protein levels were assessed in 13 CC cell lines and 23 consecutive CC specimens by real-time quantitative polymerase chain reaction, western blotting, and immunohistochemistry. Methylation of the NOL7 promoter was analyzed by bisulfite sequencing and mutations were identified through direct sequencing. A CpG island with multiple CpG dinucleotides spanned the 5' untranslated region and first exon of NOL7. However, bisulfite sequencing failed to identify persistent sites of methylation. Mutational sequencing revealed that 40% of the CC specimens and 31% of the CC cell lines harbored somatic mutations that may affect the in vivo function of NOL7. Endogenous NOL7 mRNA and protein expression in CC cell lines were significantly decreased in 46% of the CC cell lines. Finally, immunohistochemistry demonstrated strong NOL7 nucleolar staining in normal tissues that decreased with histologic progression toward CC. NOL7 is inactivated in CC in accordance with the Knudson 2-hit hypothesis through loss of heterozygosity and mutation. Together with evidence of its in vivo tumor suppression, these data support the hypothesis that NOL7 is the legitimate tumor suppressor gene located on 6p23.
Class I TCP Transcription Factor AtTCP8 Modulates Key Brassinosteroid-Responsive Genes
Creator:
McInturf, S., Mendoza-Cozatl, D., Collins, Carina, Chlebowski, M., Gassman, W., Su, J., Cseke, L., and Spears, B.
Related Url Tesim:
Available from library catalog: https://marianunivindianapolis.on.worldcat.org/oclc/9564391473, Preprint from bioRxiv: https://www.biorxiv.org/content/10.1101/2021.12.21.473710v1, and Available from publisher: https://academic.oup.com/plphys/article-abstract/190/2/1457/6648405?redirectedFrom=fulltext
Description:
The plant-specific TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factor family is most closely associated with regulating plant developmental programs. Recently, TCPs were also shown to mediate host immune signaling, both as targets of pathogen virulence factors and as regulators of plant defense genes. However, comprehensive characterization of TCP gene targets is still lacking. Loss of function of the class I TCP gene AtTCP8 attenuates early immune signaling and, when combined with mutations in AtTCP14 and AtTCP15, additional layers of defense signaling in Arabidopsis (Arabidopsis thaliana). Here, we focus on TCP8, the most poorly characterized of the three to date. We used chromatin immunoprecipitation and RNA sequencing to identify TCP8-bound gene promoters and differentially regulated genes in the tcp8 mutant; these datasets were heavily enriched in signaling components for multiple phytohormone pathways, including brassinosteroids (BRs), auxin, and jasmonic acid. Using BR signaling as a representative example, we showed that TCP8 directly binds and activates the promoters of the key BR transcriptional regulatory genes BRASSINAZOLE-RESISTANT1 (BZR1) and BRASSINAZOLE-RESISTANT2 (BZR2/BES1). Furthermore, tcp8 mutant seedlings exhibited altered BR-responsive growth patterns and complementary reductions in BZR2 transcript levels, while TCP8 protein demonstrated BR-responsive changes in subnuclear localization and transcriptional activity. We conclude that one explanation for the substantial targeting of TCP8 alongside other TCP family members by pathogen effectors may lie in its role as a modulator of BR and other plant hormone signaling pathways.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
Language:
English
Publisher:
Oxford University Press and American Society of Plant Biologists
Identifier:
DOI: https://doi.org/10.1101/2021.12.21.473710 and DOI: https://doi.org/10.1093/plphys/kiac332
Type:
Article
Keyword:
plant hormone signaling pathways, host immune signaling, I TCP gene AtTCP8, and TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP)
A conceptual framework for host-associated microbiomes of hybrid organisms
Creator:
Camper, B.T., Laughlin, Z., Malagon, D., Denton, Robert, and Bewick, S.
Related Url Tesim:
Available from the publisher: https://besjournals.onlinelibrary.wiley.com/doi/full/10.1111/2041-210X.14279 and Available from the library catalog: https://marianunivindianapolis.on.worldcat.org/oclc/10239960997
Description:
1. Hybridization between organisms from evolutionarily distinct lineages can have profound consequences on organismal ecology, with cascading effects on fitness and evolution. Most studies of hybrid organisms have focused on organismal traits, for example, various aspects of morphology and physiology. However, with the recent emergence of holobiont theory, there has been growing interest in understanding how hybridization impacts and is impacted by host-associated microbiomes. Better understanding of the interplay between host hybridization and host-associated microbiomes has the potential to provide insight into both the roles of host-associated microbiomes as dictators of host performance as well as the fundamental rules governing host-associated microbiome assembly. Unfortunately, there is a current lack of frameworks for understanding the structure of host-associated microbiomes of hybrid organisms.
2. In this paper, we develop four conceptual models describing possible relationships between the host-associated microbiomes of hybrids and their progenitor or ‘parent’ taxa. We then integrate these models into a quantitative ‘4H index’ and present a new R package for calculation, visualization and analysis of this index.
3. We demonstrate how the 4H index can be used to compare hybrid microbiomes across disparate plant and animal systems. Our analyses of these data sets show variation in the 4H index across systems based on host taxonomy, host site and microbial taxonomic group.
4. Our four conceptual models, paired with our 4H index and associated visualization tools, facilitate comparison across hybrid systems. This, in turn, allows for systematic exploration of how different aspects of host hybridization impact the host-associated microbiomes of hybrid organisms.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
License Tesim:
https://creativecommons.org/licenses/by-nc/4.0/
Language:
English
Publisher:
John Wiley & Sons Ltd and British Ecological Society
Identifier:
DOI: https://doi.org/10.1111/2041-210X.14279
Type:
Article
Keyword:
hybridization , organismal ecology, evolution, holobiont theory, and host-associated microbiomes
Conserved chromatin and repetitive patterns reveal slow genome evolution in frogs
Creator:
Dredeson, J., Mudd, A., Hanken, J., Kerdivel, G., Medina-Ruiz, S., Buisine, N., Sachs, L., Buchholz, D., Kwon, T., Smith-Parker, H., Gridi-Papp, M., Ryan, M., Plott, C., Denton, Robert D., Malone, J., Wallingford, J., Mitros, T., Straight, A., Heald, R., Hockemeyer, D., Harland, R. , Rokhsar, D., Smith, O., Grimwood, J., Miller, K., Lyons, J, Batra, S., Park, J., Berkoff, K., Schmutz, J., Aguierre-Figueroa, G., Khokha, M., Lane, M., Philipp,I., and Laslo, M
Related Url Tesim:
Available from the publisher: https://www.nature.com/articles/s41467-023-43012-9 and Available from the library catalog: https://marianunivindianapolis.on.worldcat.org/oclc/10130428461
Description:
Frogs are an ecologically diverse and phylogenetically ancient group of anuran amphibians that include important vertebrate cell and developmental model systems, notably the genus Xenopus. Here we report a high-quality reference genome sequence for the western clawed frog, Xenopus tropicalis, along with draft chromosome-scale sequences of three distantly related emerging model frog species, Eleutherodactylus coqui, Engystomops pustulosus, and Hymenochirus boettgeri. Frog chromosomes have remained remarkably stable since the Mesozoic Era, with limited Robertsonian (i.e., arm-preserving) translocations and end-to-end fusions found among the smaller chromosomes. Conservation of synteny includes conservation of centromere locations, marked by centromeric tandem repeats associated with Cenp-a binding surrounded by pericentromeric LINE/L1 elements. This work explores the structure of chromosomes across frogs, using a dense meiotic linkage map for X. tropicalis and chromatin conformation capture (Hi-C) data for all species. Abundant satellite repeats occupy the unusually long (~20 megabase) terminal regions of each chromosome that coincide with high rates of recombination. Both embryonic and differentiated cells show reproducible associations of centromeric chromatin and of telomeres, reflecting a Rabl-like configuration. Our comparative analyses reveal 13 conserved ancestral anuran chromosomes from which contemporary frog genomes were constructed.
Publisher citation page contains supplementary files and source data for download.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
License Tesim:
https://creativecommons.org/licenses/by/4.0/
Language:
English
Publisher:
Springer Nature
Identifier:
DOI: https://doi.org/10.1038/s41467-023-43012-9
Type:
Article
Keyword:
centomeres, evolutionary genetics, genome, molecular evolution, and Xenopus tropicalis
We conducted a study of the diet of the federally endangered Indiana bat (Myotis sodalis) at an urban/rural interface near Indianapolis International Airport in summer 2004. We used two 1-m2quadrats covered with window screening to collect guano under a known roost tree. We then examined 20 fecal pellets/week until the bats abandoned the roost (i.e., 13 weeks). The most common orders of insects eaten were: Lepidoptera (35.3% volume, 84.6% frequency), Diptera (27.9%, 73.2%), Coleoptera (16.9%, 62.9%), and Hymenoptera (10.9%, 45.9%). Components of the diet at the ordinal level varied significantly over time. Despite the developed nature of the site, the diet consisted of the same components reported in earlier studies.
DSG3 as a biomarker for the ultrasensitive detection of occult lymph node metastasis in oral cancer using nanostructured immunoarrays.
Creator:
Singh, Bhuvanesh, Marsh, Christina A., Sinha,Uttam K., Rusling, James F., Malhotra, Ruchika, Veenstra, Timothy D., Doci, Colleen L., Gutkind, J. Silvio, Patel, Vyomesh, Nathan, Cherie-Ann O., Martin, Daniel, and Molinolo, Alfredo A.
Related Url Tesim:
Originally Published in Oral Oncology here: https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S1368837512002618?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1368837512002618%3Fshowall%3Dtrue&referrer=https:%2F%2Fpubmed.ncbi.nlm.nih.gov%2F and https://pubmed.ncbi.nlm.nih.gov/23010602/
Description:
OBJECTIVES: The diagnosis of cervical lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) patients constitutes an essential requirement for clinical staging and treatment selection. However, clinical assessment by physical examination and different imaging modalities, as well as by histological examination of routine lymph node cryosections can miss micrometastases, while false positives may lead to unnecessary elective lymph node neck resections. Here, we explored the feasibility of developing a sensitive assay system for desmoglein 3 (DSG3) as a predictive biomarker for lymph node metastasis in HNSCC. MATERIALS AND METHODS: DSG3 expression was determined in multiple general cancer- and HNSCC-tissue microarrays (TMAs), in negative and positive HNSCC metastatic cervical lymph nodes, and in a variety of HNSCC and control cell lines. A nanostructured immunoarray system was developed for the ultrasensitive detection of DSG3 in lymph node tissue lysates. RESULTS: We demonstrate that DSG3 is highly expressed in all HNSCC lesions and their metastatic cervical lymph nodes, but absent in non-invaded lymph nodes. We show that DSG3 can be rapidly detected with high sensitivity using a simple microfluidic immunoarray platform, even in human tissue sections including very few HNSCC invading cells, hence distinguishing between positive and negative lymph nodes. CONCLUSION: We provide a proof of principle supporting that ultrasensitive nanostructured assay systems for DSG3 can be exploited to detect micrometastatic HNSCC lesions in lymph nodes, which can improve the diagnosis and guide in the selection of appropriate therapeutic intervention modalities for HNSCC patients.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
Language:
English
Publisher:
Elsevier
Identifier:
10.1016/j.oraloncology.2012.08.001, PMCID: PMC3546158 , and PMID: 23010602
Dual inhibition of vascular endothelial growth factor receptor and epidermal growth factor receptor is an effective chemopreventive strategy in the mouse 4-NQO model of oral carcinogenesis.
Creator:
Mankame, Tanmayi P., Zhou, Guolin, Wroblewski, Kristen, Lingen, Mark W., Doci, Colleen L., and Hasina, Rifat
Related Url Tesim:
https://cancerpreventionresearch.aacrjournals.org/content/3/11/1493.long and https://pubmed.ncbi.nlm.nih.gov/20978113/
Description:
Despite recent therapeutic advances, several factors, including field cancerization, have limited improvements in long-term survival for oral squamous cell carcinoma (OSCC). Therefore, comprehensive treatment plans must include improved chemopreventive strategies. Using the 4-nitroquinoline 1-oxide (4-NQO) mouse model, we tested the hypothesis that ZD6474 (Vandetanib, ZACTIMA) is an effective chemopreventive agent. CBA mice were fed 4-NQO (100 μg/mL) in their drinking water for 8 weeks and then randomized to no treatment or oral ZD6474 (25 mg/kg/d) for 24 weeks. The percentage of animals with OSCC was significantly different between the two groups (71% in control and 12% in the ZD6474 group; P ≤ 0.001). The percentage of mice with dysplasia or OSCC was significantly different (96% in the control and 28% in the ZD6474 group; P ≤ 0.001). Proliferation and microvessel density scores were significantly decreased in the ZD6474 group (P ≤ 0.001 for both). Although proliferation and microvessel density increased with histologic progression in control and treatment cohorts, epidermal growth factor receptor and vascular endothelial growth factor receptor-2 phosphorylation was decreased in the treatment group for each histologic diagnosis, including mice harboring tumors. OSCC from ZD6474-treated mice exhibited features of epithelial to mesenchymal transition, as shown by loss E-cadherin and gain of vimentin protein expression. These data suggest that ZD6474 holds promise as an OSCC chemopreventive agent. They further suggest that acquired resistance to ZD6474 may be mediated by the expression of an epithelial to mesenchymal transition phenotype. Finally, the data suggests that this model is a useful preclinical platform to investigate the mechanisms of acquired resistance in the chemopreventive setting.
Rights statement:
http://rightsstatements.org/vocab/InC/1.0/
Language:
English
Identifier:
10.1158/1940-6207.CAPR-10-0135, PMCID: PMC3408865 , and PMID: 20978113
Type:
Article
Keyword:
field cancerization, acquired resistance, chemopreventive strategies, and oral squamous cell carcinoma
Effectiveness of a network Open House model to recruit trainees to post-baccalaureate STEM programs
Creator:
Aoki, S., Lewellyn, L., Justice, Sarah, Mordan-McCombs, S., Tewari, N., Cantu, J., Seiser, R., Lakhani, A., and Kowalski, J.
Related Url Tesim:
Available from the publisher: https://www.biorxiv.org/content/10.1101/2024.01.08.574670v1
Description:
Post-baccalaureate (post-bac) programs can have a positive impact on science training and STEM career opportunities for junior trainees. A goal for many of these sponsored programs is to increase research exposure for underrepresented minorities, a group that can include African American, Hispanic, Native American, and first-generation college students, among others. Recruiting underrepresented minorities to post-bac programs can be challenging, for reasons that include a lack of available research opportunities, time to pursue these experiences, and awareness of available programs. To this end, an Open House event was created to inform and excite potential students for future post-bac programs. Students were recruited from partnering Minority Serving Institutions (MSIs) to attend a two-day event at a primarily undergraduate institution (PUI) and a research-intensive R1 institution. The students visited both campuses, were informed about post-bac programs and potential research opportunities, and met with faculty, current graduate students, and a former post-bac scholar. Transportation, lodging, and meals were provided. Visiting students completed voluntary pre- and post-surveys. Results indicated that attendees, the majority of whom were underrepresented minorities in STEM, left the event with an increased understanding about post-bac programs and their benefits to a career in STEM and that their attendance at the event made it more likely they would apply to available post-bac programs. Thus, this work demonstrates that in-person events involving integrative partnerships across multiple universities are effective strategies for increasing awareness of opportunities available to students post-graduation and for recruiting underrepresented groups in STEM to post-bac programs.