scholarly journals The impact of the ovarian microenvironment on the anti-tumor effect of SPARC on ovarian cancer1This article is part of Special Issue entitled Asilomar Chromatin and has undergone the Journal’s usual peer review process.

2012 ◽  
Vol 90 (1) ◽  
pp. 96-107 ◽  
Author(s):  
James B. Greenaway ◽  
Anne Koehler ◽  
Christopher A. McCulloch ◽  
James Petrik ◽  
Theodore J. Brown ◽  
...  

A lack of host-derived SPARC promotes disease progression in an intraperitoneal (IP) ID8 mouse model of epithelial ovarian cancer (EOC). Since orthotopic injection (OT) of ID8 cells better recapitulates high-grade serous cancer, we examined the impact of host-derived SPARC following OT injection. Sparc−/− and wild-type (WT) mice were injected with ID8 cells either OT or IP and tumors were analyzed at the moribund stage. Sparc−/− mice had reduced survival and fewer well-defined abdominal lesions compared with WT controls after IP injection, whereas no differences were observed in survival or abdominal lesions between Sparc−/− and WT mice after OT injection. No differences in mass or collagen content were observed in ovarian tumors between OT-injected Sparc−/− and WT mice. The abdominal wall of the IP-injected Sparc−/− mice exhibited immature and less abundant collagen fibrils compared with WT mice both in injected and non-injected controls. In contrast to human EOC, SPARC was expressed by the tumor cells but was absent in reactive stroma of WT mice. Exposure to the ovarian microenvironment through OT injections alters the metastatic behaviour of ID8 cells, which is not affected by the absence of host-derived SPARC.

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
David W. Chan ◽  
Wai-Yip Lam ◽  
Fushun Chen ◽  
Mingo M. H. Yung ◽  
Yau-Sang Chan ◽  
...  

Abstract Background In contrast to stable genetic events, epigenetic changes are highly plastic and play crucial roles in tumor evolution and development. Epithelial ovarian cancer (EOC) is a highly heterogeneous disease that is generally associated with poor prognosis and treatment failure. Profiling epigenome-wide DNA methylation status is therefore essential to better characterize the impact of epigenetic alterations on the heterogeneity of EOC. Methods An epigenome-wide association study was conducted to evaluate global DNA methylation in a retrospective cohort of 80 mixed subtypes of primary ovarian cancers and 30 patients with high-grade serous ovarian carcinoma (HGSOC). Three demethylating agents, azacytidine, decitabine, and thioguanine, were tested their anti-cancer and anti-chemoresistant effects on HGSOC cells. Results Global DNA hypermethylation was significantly associated with high-grade tumors, platinum resistance, and poor prognosis. We determined that 9313 differentially methylated probes (DMPs) were enriched in their relative gene regions of 4938 genes involved in small GTPases and were significantly correlated with the PI3K-AKT, MAPK, RAS, and WNT oncogenic pathways. On the other hand, global DNA hypermethylation was preferentially associated with recurrent HGSOC. A total of 2969 DMPs corresponding to 1471 genes were involved in olfactory transduction, and calcium and cAMP signaling. Co-treatment with demethylating agents showed significant growth retardation in ovarian cancer cells through differential inductions, such as cell apoptosis by azacytidine or G2/M cell cycle arrest by decitabine and thioguanine. Notably, azacytidine and decitabine, though not thioguanine, synergistically enhanced cisplatin-mediated cytotoxicity in HGSOC cells. Conclusions This study demonstrates the significant association of global hypermethylation with poor prognosis and drug resistance in high-grade EOC and highlights the potential of demethylating agents in cancer treatment. Graphic abstract


Symmetry ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 501 ◽  
Author(s):  
Edmundas Kazimieras Zavadskas ◽  
Romualdas Bausys ◽  
and Jurgita Antucheviciene

A topic of utmost importance in civil engineering is finding optimal solutions throughout the life cycle of buildings and infrastructural objects, including their design, manufacturing, use, and maintenance. Operational research, management science, and optimisation methods provide a consistent and applicable groundwork for engineering decision-making. These topics have received the interest of researchers, and, after a rigorous peer-review process, eight papers have been published in the current special issue. The articles in this issue demonstrate how solutions in civil engineering, which bring economic, social and environmental benefits, are obtained through a variety of methodologies and tools. Usually, decision-makers need to take into account not just a single criterion, but several different criteria and, therefore, multi-criteria decision-making (MCDM) approaches have been suggested for application in five of the published papers; the rest of the papers apply other research methods. The methods and application case studies are shortly described further in the editorial.


2017 ◽  
Vol 12 (3) ◽  
pp. 159
Author(s):  
Melissa Goertzen

A Review of: Riehle, C. F., & Hensley, M. K. (2017). What do undergraduate students know about scholarly communication?: A mixed methods study. Portal: Libraries and the Academy, 17(1), 145–178. http://dx.doi.org/10.1353/pla.2017.0009 Abstract Objective – To examine undergraduate student researchers’ perception and understanding of scholarly communication practices and issues. Design – Mixed method study involving a survey and semi-structured interviews. Setting – Two major undergraduate universities in the Midwest region of the United States. Subjects – Undergraduate students who participated in or had completed undergraduate research experiences with faculty mentors. Method – The method was first approved by Institutional Review Board offices at both campuses involved in the study. Then, students received invitations to participate in a survey via email (Campus 1 = 221 students; Campus 2 = 345 students). Identical online surveys ran separately on each campus; both remained open for a period of three weeks. All respondents received a reminder email one week before the survey closed. Participants answered twelve questions related to demographics and scholarly communication practices. The survey examined knowledge and experience across five areas: the peer review process, author and publisher rights, publication and access models, impact of research, and data management. All students who completed the survey were entered in a drawing for a $50 Amazon card. The response rates were 34.8% (Campus 1) and 18.6% (Campus 2). Surveys on both campuses were administered using different software: campus 1 utilized Qualtrics survey software while campus 2 used an institution-specific survey software. Data sets were normed and merged later in the study to enable comparison and identify broad themes. Survey respondents were also invited to participate in a 15 to 20 minute follow-up interview and were compensated with a $20 Amazon gift card. The interviews consisted of four open-ended questions that further examined students’ knowledge of scholarly communication practices. The researchers coded interview transcripts and identified themes. Qualitative software was used to analyze the surveys and assess coder agreement. Finally, connections and anomalies between survey and interview results were explored. Main Results – Quantitative and qualitative data collected during the study indicate that students were most confident in their understanding of the peer-review process and data management but felt less confident in their knowledge of author and publisher rights, publication and access models, and determining the impact of scholarly research publication. In addition, they value instruction related to scholarly communication topics like the peer-review process, publication models, and data management. However, few students feel confident in their current level of knowledge or ability surrounding the previously mentioned topics. Study findings suggest that this knowledge gap is based on a lack of training or discussion of scholarly communication topics in relation to students’ research activities. Results also suggest that undergraduate students have difficulty articulating their rights as authors and their scholarly communication practices. In many cases, skill sets like data management are learned through trial and error while students progress through the research process. In some cases, faculty mentors have misperceptions and assumptions about undergraduate students’ knowledge and abilities regarding scholarly communication practices. This can create challenges for undergraduate students as they attempt to make informed decisions about research activities based on a limited foundation of experience or information. Finally, results indicate that undergraduate student researchers do not currently view the library as a place to learn about scholarly communication practices. The authors suggest that by forming strategic relationships with undergraduate research program directors, faculty, and graduate student mentors, librarians are in a prime position to incorporate scholarly communication practices into information literacy sessions or provide point-of-need coaching. Conclusion – The researchers conclude that academic libraries are in a unique position to support overarching research, teaching, and learning goals within the academic community. By developing programs that support information literacy and scholarly communication, libraries demonstrate value and align goals with teaching and learning priorities within the higher education community as a whole. Through this work, librarians support students as knowledge creators and advocate for training that emphasizes data literacy, copyright and authors’ rights, and the impact of research within specific disciplines.


2011 ◽  
Vol 89 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Tamara L. Caterino ◽  
Jeffrey J. Hayes

Linker histones are multifunctional proteins that are involved in a myriad of processes ranging from stabilizing the folding and condensation of chromatin to playing a direct role in regulating gene expression. However, how this class of enigmatic proteins binds in chromatin and accomplishes these functions remains unclear. Here we review data regarding the H1 structure and function in chromatin, with special emphasis on the C-terminal domain (CTD), which typically encompasses approximately half of the mass of the linker histone and includes a large excess of positively charged residues. Owing to its amino acid composition, the CTD was previously proposed to function in chromatin as an unstructured polycation. However, structural studies have shown that the CTD adopts detectable secondary structure when interacting with DNA and macromolecular crowding agents. We describe classic and recent experiments defining the function of this domain in chromatin folding and emerging data indicating that the function of this protein may be linked to intrinsic disorder.


2018 ◽  
Vol 149 ◽  
pp. 212
Author(s):  
J. Gillen ◽  
M. Rowland ◽  
A.Y. Liu ◽  
S. Vesely ◽  
B. Powell ◽  
...  

2010 ◽  
Vol 88 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Tobias Haslberger ◽  
Bernd Bukau ◽  
Axel Mogk

The oligomeric AAA+ chaperones ClpB/Hsp104 mediate the reactivation of aggregated proteins, an activity that is crucial for the survival of cells during severe stress. Hsp104 is also essential for the propagation of yeast prions by severing prion fibres. Protein disaggregation depends on the cooperation of ClpB/Hsp104 with a cognate Hsp70 chaperone system. While Hsp70 chaperones are also involved in prion propagation, their precise role is much less well defined compared with its function in aggregate solubilization. Therefore, it remained unclear whether both ClpB/Hsp104 activities are based on common or different mechanisms. Novel data show that ClpB/Hsp104 uses a motor threading activity to remodel both protein aggregates and prion fibrils. Moreover, transfer of both types of substrates to the ClpB/Hsp104 processing pore site requires initial substrate interaction of Hsp70. Together these data emphasize the similarity of thermotolerance and prion propagation pathways and point to a shared mechanistic principle of Hsp70–ClpB/Hsp104-mediated solubilization of amorphous and ordered aggregates.


2012 ◽  
Vol 90 (3) ◽  
pp. 457-467 ◽  
Author(s):  
Theresa J. Ochoa ◽  
Alonso Pezo ◽  
Karen Cruz ◽  
Elsa Chea-Woo ◽  
Thomas G. Cleary

Much has been learned in recent years about the mechanisms by which breastfeeding improves child health and survival. However, there has been little progress in using these insights to improve pediatric care. The aim of this study was to review all clinical studies of lactoferrin (LF) in children in an effort to determine which interventions may improve pediatric care or require further research. We conducted a systematic and critical review of published literature and found 19 clinical studies that have used human or bovine LF for different outcomes: iron metabolisms and anemia (6 studies), fecal flora (5 studies), enteric infections (3 studies), common pediatric illnesses (1 study), immunomodulation (3 studies), and neonatal sepsis (1 study). Although the efficacies have varied in each trial, the main finding of all published studies is the safety of the intervention. Protection against enteric infections and neonatal sepsis are the most likely biologically relevant activities of LF in children. Future studies on neonatal sepsis should answer critically important questions. If the data from these sepsis studies are proven to be correct, it will profoundly affect the treatment of low birth weight neonates and will aid in the reduction of child mortality worldwide.


2009 ◽  
Vol 34 (3) ◽  
pp. 488-492 ◽  
Author(s):  
Terry E. Graham

While scientists have routinely measured muscle glycogen in many metabolic situations for over 4 decades, there is surprisingly little known regarding its regulation. In the past decade, considerable evidence has illustrated that the carbohydrate stores in muscle are not homogeneous, and it is very likely that metabolic pools exist or that each granule has independent regulation. The fundamental aspects appear to be associated with a complex set of proteins that associate with both the granule and each other in a dynamic fashion. Some of the proteins are enzymes and others play scaffolding roles. A number of the proteins can translocate, depending on the metabolic stimulus. These various processes appear to be the mechanisms that give the glycogen granule precise yet dynamic regulation. This may also allow the stores to serve as an important metabolic regulator of other metabolic events.


Coatings ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1113
Author(s):  

Following acceptance of the Special Issue article by the Guest Editor, El-Sayed Abd El-Aziz, concerns were raised regarding the integrity of the peer review process [...]


Coatings ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1117
Author(s):  

Following acceptance of the Special Issue article by the Guest Editor, El-Sayed Abd El-Aziz, concerns were raised regarding the integrity of the peer review process [...]


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