¹³¹I-Anti CD20 Radioimmunotherapy of Relapsed or Refractory Non-Hodgkins Lymphoma: A Phase II Clinical Trial of a Nonmyeloablative Dose Regimen of Chimeric Rituximab Radiolabeled in a Hospital

Turner, J. Harvey,Martindale, Andrew A.,Boucek, Jan,Claringbold, Phillip G.,Leahy, Michael F. Mary Ann Liebert 2003 Cancer Biotherapy & Radiopharmaceuticals Vol.18 No.4

<P>In order to increase the availability and affordability of radioimmunotherapy of refractory or relapsed non-Hodgkins lymphoma, we developed and evaluated radioiodinated rituximab in an ongoing physician-sponsored Phase II Clinical Trial. The chimeric 1gG(1) anti CD 20 monoclonal antibody rituximab was radiolabeled with iodine-131 using a modified Chloramine T method with high radiochemical purity (98% +/- 0.82) and preservation of immunoreactivity. All patients received therapeutic loading doses of unlabeled rituximab (375 mg/m(2)) immediately prior to administration of tracer (200 MBq (131)I) or therapy (1.7-4.3 GBq (131)I) activities of (131)I-rituximab to provide additive immunotherapy and enhance tumor uptake of the radiolabeled antibody. Objective response rate (ORR) was 71% in 35 patients with a median follow-up of 14 months (range 4-28 months). Complete remission (CR) was achieved in 54% of patients, with median duration 20 months. Toxicity evaluation included an additional 7 patients followed for at least 3 months. Tracer dosimetry studies were performed in each patient and the whole body radiation absorbed dose was limited to a mean prescribed dose (MPD) of 0.75 Gy. Myelosuppression was reversible and in only 2 of 42 patients was grade IV hematological toxicity observed. No hemopoietic support was required in any patient. There was no instance of hemorrhage or infection in this group of patients in each of whom individual prospective dosimetry was performed prior to (131)I rituximab radioimmunotherapy for relapsed or refractory non-Hodgkins lymphoma.</P>

Unifying yet dividing: voices of pussyhat maker–wearers who participated in the 2017 Women’s Marches

Nancy L. Malcom,Addie K. Martindale,V. Ann Paulins,Julie L. Hillery,Alexandra Howell 한국의류학회 2020 Fashion and Textiles Vol.7 No.1

On January 21, 2017, several million protesters took part in the “Women’s March on Washington” and its more than 400 sister Marches held in cities throughout the U.S. and across the globe. One enduring image of these Marches was the (often pink) pussyhat. In this qualitative study we examine broader issues of inclusion and exclusion within craftivism and take a closer look at the way craftivism supported, and potentially detracted from, its intended purpose as a unifying symbol of the Marches. From a dataset of 511 surveys distributed and collected online, 71 “maker–wearers” were identified and investigated for this study. While our overarching question focused on the role of craftivism related to the inaugural March and the pussyhat, we seek to understand not only the voices of craftivists, but also the voices of marchers who reported negative and/or controversial associations with the pussyhat. Building on previous findings that the majority of marchers we surveyed perceive the pussyhat as an anti-Trump symbol that represented women’s power, strength, and solidarity, a small number of our respondents and emergent voices in mainstream media have indicated concerns about potential racism and trans person exclusion represented by the pussyhat. We conclude that even as the pussyhat is recognized as a unifying symbol, it is simultaneously representative of exclusionary, potentially divisive practices within both craftivism and feminism. As awareness of the pussyhat’s problematic symbolism is spreading, new conversations have spawned about intersectionality and the implementation of more inclusive practices.

The RNA-binding Protein HuD Regulates Autophagosome Formation in Pancreatic β Cells by Promoting Autophagy-related Gene 5 Expression

Kim, Chongtae,Kim, Wook,Lee, Heejin,Ji, Eunbyul,Choe, Yun-Jeong,Martindale, Jennifer L.,Akamatsu, Wado,Okano, Hideyuki,Kim, Ho-Shik,Nam, Suk Woo,Gorospe, Myriam,Lee, Eun Kyung American Society for Biochemistry and Molecular Bi 2014 The Journal of biological chemistry Vol.289 No.1

<P>Tight regulation of autophagy is critical for the fate of pancreatic β cells. The autophagy protein ATG5 is essential for the formation of autophagosomes by promoting the lipidation of microtubule-associated protein LC3 (light chain 3). However, little is known about the mechanisms that regulate ATG5 expression levels. In this study, we investigated the regulation of ATG5 expression by HuD. The association of HuD with <I>ATG5</I> mRNA was analyzed by ribonucleoprotein complex immunoprecipitation and biotin pulldown assays. HuD expression levels in pancreatic β cells were knocked down via siRNA, elevated by overexpression of a HuD-expressing plasmid. The expression levels of HuD, ATG5, LC3, and β-actin were determined by Western blot and quantitative RT-PCR analysis. Autophagosome formation was assessed by fluorescence microscopy in GFP-LC3-expressing cells and in pancreatic tissues from WT and HuD-null mice. We identified <I>ATG5</I> mRNA as a post-transcriptional target of the mammalian RNA-binding protein HuD in pancreatic β cells. HuD associated with the 3′-UTR of the <I>ATG5</I> mRNA. Modulating HuD abundance did not alter <I>ATG5</I> mRNA levels, but HuD silencing decreased <I>ATG5</I> mRNA translation, and, conversely, HuD overexpression enhanced <I>ATG5</I> mRNA translation. Through its effect on ATG5, HuD contributed to the lipidation of LC3 and the formation of LC3-positive autophagosomes. In keeping with this regulatory paradigm, HuD-null mice displayed lower ATG5 and LC3 levels in pancreatic β cells. Our results reveal HuD to be an inducer of ATG5 expression and hence a critical regulator of autophagosome formation in pancreatic β cells.</P>

AUF1 promotes let-7b loading on Argonaute 2

Yoon, Je-Hyun,Jo, Myung Hyun,White, Elizabeth J.F.,De, Supriyo,Hafner, Markus,Zucconi, Beth E.,Abdelmohsen, Kotb,Martindale, Jennifer L.,Yang, Xiaoling,Wood III, William H.,Shin, Yu Mi,Song, Ji-Joon,T Cold Spring Harbor Laboratory Press 2015 Genes & development Vol.29 No.15

<P>Yoon et al. discovered that RBP AU-rich-binding factor 1 (AUF1) promotes let-7b loading onto Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex (RISC). In turn, AGO2–let-7 triggered target mRNA decay.</P><P>Eukaryotic gene expression is tightly regulated post-transcriptionally by RNA-binding proteins (RBPs) and microRNAs. The RBP AU-rich-binding factor 1 (AUF1) isoform p37 was found to have high affinity for the microRNA let-7b in vitro (<I>K</I><SUB>d</SUB> = ∼6 nM) in cells. Ribonucleoprotein immunoprecipitation, in vitro association, and single-molecule-binding analyses revealed that AUF1 promoted let-7b loading onto Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex (RISC). In turn, AGO2–let-7 triggered target mRNA decay. Our findings uncover a novel mechanism by which AUF1 binding and transfer of microRNA let-7 to AGO2 facilitates let-7-elicited gene silencing.</P>

WIG1 is crucial for AGO2-mediated <i>ACOT7</i> mRNA silencing via miRNA-dependent and -independent mechanisms

Lee, Hyung Chul,Jung, Seung Hee,Hwang, Hyun Jung,Kang, Donghee,De, Supriyo,Dudekula, Dawood B.,Martindale, Jennifer L.,Park, Byungkyu,Park, Seung Kuk,Lee, Eun Kyung,Lee, Jeong-Hwa,Jeong, Sunjoo,Han, K Oxford University Press 2017 Nucleic acids research Vol.45 No.11

<P><B>Abstract</B></P><P>RNA-binding proteins (RBPs) are involved in mRNA splicing, maturation, transport, translation, storage and turnover. Here, we identified <I>ACOT7</I> mRNA as a novel target of human WIG1. <I>ACOT7</I> mRNA decay was triggered by the microRNA miR-9 in a WIG1-dependent manner via classic recruitment of Argonaute 2 (AGO2). Interestingly, AGO2 was also recruited to <I>ACOT7</I> mRNA in a WIG1-dependent manner in the absence of miR-9, which indicates an alternative model whereby WIG1 controls AGO2-mediated gene silencing. The WIG1–AGO2 complex attenuated translation initiation via an interaction with translation initiation factor 5B (eIF5B). These results were confirmed using a WIG1 tethering system based on the MS2 bacteriophage coat protein and a reporter construct containing an MS2-binding site, and by immunoprecipitation of WIG1 and detection of WIG1-associated proteins using liquid chromatography-tandem mass spectrometry. We also identified WIG1-binding motifs using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation analyses. Altogether, our data indicate that WIG1 governs the miRNA-dependent and the miRNA-independent recruitment of AGO2 to lower the stability of and suppress the translation of <I>ACOT7</I> mRNA.</P>