bluuebunny/crossref_metadata_2025_split huggingface dataset:
1,25‐Dihydroxyvitamin D regulates lipid metabolism and metastasis in breast epithelial cells (261.6)
Authors: Barnard Alle , Buhman Kim , Parikh Mukti , Kirshner Julia , Teegarden Dorothy 
Published: June 2021

The purpose of these studies was to investigate the 1,25‐dihydroxyvitamin D (1,25D) regulation of breast epithelial cell lipid metabolism and breast to bone metastasis. The untransformed, MCF10A (10A), and metastatic, MCF10CA1a, breast epithelial cells were employed for these studies. Lipid accumulation was greater in MCF10CA1a cells compared to 10A cells as shown by oil red O staining, thin layer chromatography and colorimetric triglyceride analysis. Following 1,25D treatment (10nm, 48 hrs) of MCF10CA1a cells, the mRNA expression of lipid metabolism regulators fatty acid synthase (FAS), insulin inducing gene 2 (Insig2), and perilipin 2 (PLIN2) were significantly increased while carnitine palmityoltransferase 1 (CPT1a) was significantly decreased compared to vehicle. The impact of 1,25D on breast to bone metastasis was assessed employing a unique 3‐dimensional transwell matrigel invasion assay with MCF10CA1a cells. Results showed that fewer 1,25D treated cells implanted in the bone matrix compared to vehicle treated cells. In addition, 1,25D treated cells in the bone matrix retained an epithelial‐like phenotype compared to the mesenchymal‐like phenotype of the vehicle‐treated cells. These results suggest that 1,25D may regulate lipid metabolism and inhibit breast to bone metastasis.Grant Funding Source: supported by NCI CCSG CA23168
Cortactin deficiency causes increased ROCK1‐mediated actin‐contractility and decreased adrenomedullin secretion leading to enhanced endothelial permeability (278.2)
Authors: García‐Ponce Alexander , Citalán‐Madrid Alí , Vargas‐Robles Hilda , Betanzos Abigail , Rottner Klemens , Vestweber Dietmar , Schnoor Michael 
Published: June 2021

Changes in vascular permeability are a hallmark of inflammatory processes. The actin cytoskeleton plays a crucial role in regulating endothelial cell contacts and thus permeability. We showed that the actin‐binding protein cortactin (CTTN) regulates vascular permeability in vivo via Rap1. However, it is not known if the actin cytoskeleton contributes to increased permeability after loss of CTTN. In a mass spectrometric analysis, we found Rho‐kinase1 (ROCK1) to be induced 2.7‐fold in cortactin‐KO endothelium. This was confirmed by Western blot and immunolabelling of tissues from CTTN‐KO mice. Concomitantly, we observed increased phosphorylation of MLC and more stress fibers in CTTN‐KO endothelium. Secretion of the hormone adrenomedullin (ADM), which activates Rap1 and counteracts formation of stress fibers, is reduced in CTTN‐KO serum and supernatant of CTTN‐depleted endothelium. Importantly, inhibition of ROCK1 or ADM administration rescued the effect on permeability provoked by loss of CTTN. Our data suggest that CTTN controls the molecular machinery necessary for the regulation of actomyosin contractility and vascular permeability.Grant Funding Source: Supported by CONACYT 179895
Studying atypical ubiquitin chains with deubiquitinases (353.2)
Authors: Komander David 
Published: June 2021

Polyubiquitin chains can be assembled in multiple ways via eight different linkage points on ubiquitin. Single‐linkage homotypic chains but also heterotypic chains with branched or mixed linkage types regulate many aspects of the ubiquitin system, however we lack methods to study different polyubiquitin chains.We recently discovered high intrinsic linkage‐specificity in OTU domain deubiquitinases, which have evolved specific members for most ubiquitin chain types, such as the Lys11‐specific DUB Cezanne, the Met1‐specific DUB OTULIN and the Lys6/Lys11‐specific enzyme OTUD3. Together, these proteins enable a better understanding of mechanisms of linkage specificity and of the biology of atypical chains. Moreover, linkage‐specific DUBs can be used as tools to interrogate polyubiquitin chain architecture, and are especially useful for the analysis of mixed/branched polyubiquitin. In my talk, I will discuss our recent efforts to understand the biology of atypical ubiquitin chain types using linkage‐specific DUBs of the OTU family.
Accuracy of portion size reporting in the Automated Self‐Administered 24‐hour recall (ASA24) compared to interviewer‐administered recalls (36.6)
Authors: Kirkpatrick Sharon , Subar Amy , Zimmerman Thea , Douglass Deirdre , Thompson Fran , Kahle Lisa , George Stephanie , Dodd Kevin , Potischman Nancy 
Published: June 2021

Objective: To assess accuracy of portion size reporting in ASA24 compared to interviewer‐administered recalls.Methods: True intake for three meals was ascertained among 81 adults by inconspicuously weighing foods and beverages offered at a buffet before and after each participant served him/herself, as well as plate waste. Participants were randomly assigned to complete ASA24 or an interviewer‐administered Automated Multiple‐Pass Method (AMPM) recall the following day. Differences between true and reported gram weights were calculated for each consumed item for which a match was reported by respondents and averaged.Results: For foods and drinks truly consumed for which respondents reported a match (80% for ASA24 and 83% for AMPM), mean differences between true and reported portion sizes were ‐3.7 grams for ASA24 and ‐11.8 grams for AMPM (absolute differences: 40.5 grams for ASA24 and 39.8 grams for AMPM (p=0.44)). Differences for primary foods and drinks were ‐5.1 grams for ASA24 and ‐14.4 grams for AMPM, and for additions to or ingredients in multi‐component items, 0.60 grams for ASA24 and ‐6.2 grams for AMPM.Discussion: Previous analyses indicate similar match rates (i.e., the proportion of items consumed for which a corresponding food or drink was reported) and energy, nutrient and food group estimates between ASA24 and AMPM. The current results suggest that the accuracy of portion size reporting is also similar, providing further evidence that ASA24 performs well relative to interviewer‐administered recalls.
Body composition changes with calorie restriction: results from the CALERIE trial (371.6)
Authors: Das Sai Krupa , Roberts Susan , Ravussin Eric , Racette Susan , Kraus William , Saltzman Edward , Bhapkar Manjushri , Rochon James , Redman Leanne 
Published: June 2021

Calorie Restriction (CR) is the only non‐pharmacological intervention that extends lifespan in animal models. However, it is unclear whether humans can implement CR without negative effects on body composition and, if so, whether it has effects consistent with attenuated metabolic aging. Our objective was to evaluate the effect of prolonged CR on body composition changes in CALERIE, a 24 month multi‐center randomized clinical trial. 218 non‐obese (body mass index: 22‐27 kg/m²) adults aged 21 to 51 years were enrolled and randomly assigned to 25% CR (CR group) or an ad libitum control (AL group) using a 2:1 allocation. Outcomes included body weight, waist circumference, and body fat mas (FM) and fat‐free mass (FFM) assessed using dual‐energy x‐ray absorptiometry. There were significant decreases in body weight (‐7.5±0.4 vs. 0.1±0.5 kg), FM (‐5.3±0.3 vs. 0.4±0.4 kg), waist circumference (‐6.1±0.4 vs. 0.9±0.5 cm) and FFM (‐2.2±0.2 vs. ‐0.2±0.2 kg) in the CR group compared to the AL group at 24 months (all p<0.001). However, at 24 months the percentage of weight change as FFM was not significantly different between the AL and CR groups (P=0.31). CR results in substantial changes in body composition but relative losses of FFM and FM appear to be comparable to those occurring with equivalent changes in body weight as observed in this study.Grant Funding Source: National Institute on Aging: U01AG022132
Wolfberries potentiate mitophagy in the liver of obese mice (372.3)
Authors: Lin Dingbo , Medeiros Denis 
Published: June 2021

Objective: The aim is to investigate whether AMP‐activated protein kinase α2 (AMPKα2) is essential for wolfberry protective effects on mitochondrial dysfunction and subsequent hepatic steatosis in mice.Methods: Six‐week‐old male AMPKα2 knockout (KO) mice and genetic background C57BL/6J (B6) mice were fed the control, high‐fat (HD, 45% [kcal] fat), and/or HD with 5% (kcal) wolfberry diets for 18 weeks. At termination, blood and liver tissues were sampled for analysis by ELISA, HPLC, microscopy, real‐time PCR, and Western blot. Results: HD lowered hepatic lutein and zeaxanthin contents, inhibited β,β‐carotene 9,10 oxygenase 2 (BCO2) protein expression, induced mitochondrial oxidative stress as indicated by an increased reactive oxygen species level and the decreased mitochondrial membrane potential, respiratory rate, and aconitase activity. HD also suppressed mitophagy and mitochondrial biogenesis as determined by accumulation of p62, inhibited phosphorylation of Unc‐51‐like kinase 1 on Ser555, and declined expression of peroxisome proliferator‐activated receptor γ co‐activator 1 α, resulting in hepatic steatosis in B6 and KO mice. Dietary wolfberry elevated the xanthophyll concentrations and enhanced BCO2 expression, attenuated mitochondrial oxidative stress, activated AMPKα2, potentiated mitophagy and mitochondrial biogenesis, and enhanced lipid oxidation and secretion in the liver of B6 mice. Conclusion: Dietary wolfberry selectively activated AMPKα2, which resulted in enhanced mitochondrial biogenesis and potentiated mitophagy, leading to the prevention of hepatic steatosis in obese mice.Grant Funding Source: Supported by NIH NCRR Grant P20‐RR‐017686
Comparison of bioactivity between sulforaphane and neoglucobrassicin hydrolysis product in murine and human cell lines (372.5)
Authors: Das Nilanjan , Berhow Mark , Jeffery Elizabeth 
Published: June 2021

Although the biological activity of some glucosinolate (GSL) hydrolysis products from Brassica vegetables has been extensively studied, the activity of others, such as the hydrolysis product of the indole GSL neoglucobrassicin (hNeo), is relatively unknown. Here, we aim to determine how sulforaphane (SF) and hNeo act in human and murine cell lines, regarding induction of the phase II enzyme Quinone reductase (NQO1) and inhibition of nitrite (NO) generation. Haack and colleagues reported that hNeo inhibits the effect of SF on NQO1 induction in human HepG2 cells (Haack et al., 2010). Here, we confirm this and extend our knowledge to show that hNeo causes upregulation of NQO1 alone and does not inhibit SF induction of NQO1 in murine hepatoma cells. Furthermore, this species difference is reflected in phorbol 12‐myristate 13‐acetate (PMA) induced human monocytes (THP1) and in murine RAW 264.7 macrophages, where hNeo is inhibitory in human cells but additive in murine cells, both for NQO1 induction and inhibition of NO generation. These findings suggest that the mouse may not be a robust model for evaluating the human response to bioactive compounds from Brassica.Grant Funding Source: Supported by USDA/NIFA #AG 2010‐65200
Feeding style and feeding practices and toddlers’ eating behaviors (379.1)
Authors: Edelson Lisa , van der Horst Klazine , Kuenzel Johanna , Martin Nathalie 
Published: June 2021

Objective: An authoritative feeding style has been associated with healthier diets in children. This study explores which practices mothers with different feeding styles report using and if these behaviors can be observed in mealtime interactions.Methods: A questionnaire about feeding styles and practices was completed by 1005 US mothers with children of 12‐36 months. 60 families with toddlers (also 12‐36 mo.) participated in an in‐home observational study of parent‐child mealtime interactions.Results: Authoritative parents were significantly more likely to report that they model and encourage healthy eating, allow children to choose which foods to eat and to participate in meal preparation. Authoritarian mothers reported using foods as rewards and encouraging children to clean their plate. Indulgent mothers often ate with their children and gave children control over how much to eat, and were less likely to restrict intake or use foods as rewards. Uninvolved mothers reported restricting foods to control their children’s weight. Parents of older children were more demanding than those of younger children, reflecting the child’s developing ability to regulate his behavior.Conclusions: Parents of different feeding styles report different feeding practices. Parents’ reported behaviors will be compared to those observed in the behavioral study and discussed in relation to the child’s eating behaviors.
Large ethnic variations in infant and young child feeding practices: an example from Vietnamese mothers (380.7)
Authors: Nguyen Tuan , Nguyen Phuong , Tran Ngan , Nguyen Huan , Hajeebhoy Nemat 
Published: June 2021

In Viet Nam, 53 ethnic minority groups account for about 15% of the population; and stunting rates are observed to be higher amongst these ethnic groups compared to the majority Kinh population. This study is among the first to explore the ethnic variation in breastfeeding (BF) and complementary feeding (CF) practices in mothers with children < 24 months old in Viet Nam. We interviewed 1900 women as follows: Kinh (53%), E De‐Mnong (18%), Thai‐Muong (16%) and Tay‐Nung (12%). The practice of giving prelacteals was high (> 80%) in all ethnicities. Typical prelacteals included water (~50%) and infant formula (~50%). In addition, chewed rice was given by Thai Muong (44%) and honey by Tay‐Nung (38%). The exclusive BF rate was low across all ethnicities (4‐33%) with water being the main barrier. However, among the Thai Muong, chewed rice was the main barrier to exclusive BF. Fewer ethnic minority children received minimum acceptable diets (33‐52%) than the main ethnic group, the Kinh (75%). This was the result of low dietary diversity and meal frequency in Thai‐Muong, low minimum dietary diversity in E De‐Mnong, and short duration of BF and low consumption of other milk or dairy products in Tay‐Nung. Breastfeeding practices appear to be poor among all ethnicities; however, for ethnic minority groups, a greater emphasis needs to be placed on improving complementary feeding practices.Grant Funding Source: Bill & Melinda Gates Foundation, through Alive & Thrive Initiative, managed by FHI360
Keratoacanthoma biology and regression in mouse models (397.1)
Authors: Gibson‐Corley Katherine , Rogers Laura , Dupuy Adam , Meyerholz David 
Published: June 2021

We have described a novel mouse model of non‐melanoma skin cancer driven by skin‐specific expression of Zmiz1. These mice spontaneously developed keratoacanthomas and we have morphologically distinguished the biology of these tumors. Keratoacanthomas followed a growth pattern similar to that described in humans from a growth phase through a mature phase and into a regression phase. Even though the growth phase commonly had foci of atypia, high mitotic rate and minor local invasion, the tumors did not progress to malignancy. Similarly, we observed that RAG‐2‐deficient mice also developed keratoacanthomas and these followed a similar morphologic progression as did the Zmiz1 model. Using immunohistochemistry we characterized leukocyte infiltration during regression. In both models there was infiltration of macrophages and granzyme B‐immunoreactive cells. While an influx of T cells into the tumor epithelium was noted in Zimz1 mice, this was not found in RAG‐2‐deficient mice, suggesting that functional adaptive immunity is not required for regression. In these models, keratoacanthoma biology followed a consistent pattern of growth through mature and regressive phases. As commonly suggested in humans, these keratoacanthomas followed a benign course. The regression of these murine keratoacanthomas without adaptive immunity suggests that the innate immune system could be a target for treatment.Grant Funding Source: R01CA132962‐01A2 (NCI) and Aiming For a Cure Foundation
Effects in renal and cardiac tissue from CKD rat model: antioxidant evaluation of treatment with the selective endothelin‐receptor antagonist atrasentan and the combination of atrasentan with the vitamin D receptor activator (paricalcitol), and the angiot (404.4)
Authors: Muñoz Kevin , Slatopolsky Eduardo , Zhang Sarah , Finch Jane , Liapis Helen , Delmez James , Ritter Cindy , Ferder Leon , Suárez Edu 
Published: June 2021

Diabetes is the number one cause of chronic kidney disease (CKD). However, the highest mortality in CKD patients is attributed to cardiovascular disease (CVD) complications. It have been shown that processes producing reactive oxygen species (ROS) in the renal and cardiac tissues are involved in these pathologies. For instance, searching for therapies contributing to decrease ROS, in addition of controlling the CKD and CVD clinical manifestations is highly justified. In this study, we assessed the antioxidant effects of paricalcitol (vitamin D receptor activator) (UP), enalapril (angiotensin converting enzyme inhibitor) (UE), atrasentan (selective endothelin‐receptor antagonist) (UA), and the combination of these (UEAP) in cardiac and renal tissue of 5/6 nephrectomized uremic rat model. The left ventricle (LV) and kidney (KY) tissues were evaluated and compared to a uremic control (UC) and a non‐uremic control (NC). Lipid peroxidation was reduced by UEAP to levels comparable to NC in both tissues. Cardiac glutathione peroxidase activity (GPx) was significantly higher in UP and furthermore in UEAP; while UE showed the higher renal GPx. Glutathione reductase activity (GRx) at the LV was increased by UA and moreover by UE. Renal catalase activity was restored by UA and UEAP to levels comparable to NC, as did UEAP and UE at LV. In LV, UEAP showed Cu/Zn‐SOD and Mn‐SOD activity levels comparable to NC. The UE was the only one showing differences in eNOS and iNOS, confirming previous findings. Our data suggested that UA, and to a greater extent, UEAP provided increased antioxidant activity with potential to improve CDK and CVD clinical manifestations caused by ROS.Grant Funding Source: NIH R25GM096955
Genome engineering with targetable nucleases (467.1)
Authors: Carroll Dana 
Published: June 2021

We are in the midst of a revolution in genome engineering. Using zinc‐finger nucleases (ZFNs), transcription activator‐like effector nucleases (TALENs), and CRISPR/Cas nucleases, researchers have made targeted genome modifications in nearly 50 different species, with remarkable efficiency. Types of targeted manipulations include local mutagenesis, specific sequence changes, large insertions and deletions, and chromosomal rearrangements. Many model organisms have been successfully targeted, as have crop plants, livestock, and disease vectors. Clinical trials in humans using these reagents are currently under way.This presentation will take a step back and look at the origins of these targetable cleavage reagents ‐ particularly the ZFNs ‐ and the DNA repair pathways they depend on for their efficacy. Specific examples of how nuclease activity has been impeded or enhanced by cell‐ and organism‐specific biology will be provided. My lab has used Drosophila to explore some of the parameters that affect nuclease efficacy. Some of our experience with ZFNs, TALENs and CRISPR/Cas will be presented, with an emphasis on issues remaining to be resolved.
GRISTO: an integrated learning experience in Gross Anatomy and Histology for Dental Students, learning outcomes and student perspectives on curriculum change (532.4)
Authors: Hoffmann Darren , Swailes Nathan 
Published: June 2021

In a major curriculum revision we unified two separate disciplines (Gross Anatomy and Histology) into a combined course with integrated methods of instruction and assessment (GRISTO).Through creative course design, we constructively aligned content, decreased didactic lectures and increased opportunity for student engagement, group work and self‐regulated learning (flipped classrooms, peer teaching, virtual labs). In doing so we improved sequencing and cohesion between Anatomy and Histology and removed unnecessary redundancy. Implementation of GRISTO recovered 50hrs/student in the curriculum.We also hypothesized that an integrated Anatomy and Histology learning experience would lead to improved learning outcomes and student satisfaction for both disciplines.To test this hypothesis we compared student performance in assessment tasks completed after participating in pre‐GRISTO (2011) and GRISTO (2012, 2013) learning experiences. Both disciplines exhibited a right‐shift in grade distributions for GRISTO students coupled with fewer failing grades. Learning outcomes were improved in Histology (2011: 82.5%, 2012: 85.6%, 2013: 87.1%) and unchanged in Anatomy (range 87.0‐87.2%).Focused course evaluations for GRISTO (2012: n=65, 2013: n=41) revealed a strong preference for an integrated learning experience (95%) and student ratings on standardized questions reached an all‐time high.
Analysis of a high school enrichment opportunity in the anatomical sciences (534.3)
Authors: Taylor Melissa , Bareither Mary Lou 
Published: June 2021

High school students, especially students from underrepresented minority groups, may not have much exposure to anatomy in high school classrooms. These students may later be at a disadvantage when they take science college courses. This study examines the implementation of an afterschool anatomy enrichment program to a select group of high school students. The program was two semesters long and introduced students to various anatomy topics such as bones, skin, muscles, etc. They also had the opportunity to view cadavers and do some dissections. Under the guidance of undergraduate mentors from the University of Illinois‐Chicago, the high school students completed their own research projects on an anatomy topic of interest using literature and web resources and presented the projects at the spring undergraduate research forum. Students’ interests in science were surveyed after completing the enrichment program. The results of the questionnaires showed that the majority of the students enjoyed this program and wanted to pursue a science or health major in college. The results also showed that the students would recommend that future high school students partake in the program.Grant Funding Source: None
Complementary roles for Rock1 and myosin light chain kinase in actin coat compression on fused secretory vesicles (538.4)
Authors: Frick Manfred , Ehinger Konstantin , Miklavc Pika 
Published: June 2021

Alveolar type II epithelial cells secrete pulmonary surfactant via exocytosis of lamellar bodies (LBs). Surfactant is a poorly‐soluble lipo‐protein substance that does not readily diffuse out of fused LBs following opening of the fusion pore. LBs are coated with actin following fusion with the plasma membrane (PM) and actin coating and subsequent actin coat compression is essential to drive surfactant secretion. We have previously demonstrated that myosin II is involved in actin coat compression. However detailed mechanisms of myosin II activation and coat compression were still missing. Here we report that actin coat compression is a multiphasic process. High‐resolution life cell imaging and immunocytochemistry revealed that Rock1 and myosin light chain kinase 1 (MLCK) are recruited to LBs following fusion with the PM. Recruitment of Rock1 was preceded by transient recruitment and activation of Rho GTPases to the actin coat. Inhibition of Rock1 did not affect initial compression of the actin coat but significantly impaired full compression of fused vesicles. Inhibition of MLCK did not have a significant effect on actin coat compression at all. Combined inhibition of Rock1 and MLCK, however, completely blocks vesicle compression. Our data suggest that Rock1 and MLCK act via complementary pathways to regulate actin coat compression likely regulating activation of regulatory myosin II light chain.Grant Funding Source: Deutsche Forschungsgemeinschaft (DFG), BiU