bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical Signaling in Epithelial‐Mesenchymal Transition
Authors: Engler Adam , Yang Jing , Ondeck Matthew , Wei Spencer 
Published: June 2021

Mammary epithelial cells (MECs) are classically known to respond to differences in static extracellular matrix (ECM) stiffness and resemble a mesenchymal, more malignant state lacking any polarized acinar structure on stiffer ECM, i.e. Epithelial‐Mesenchymal Transition (EMT). While this is akin to the stiff mammary tumors that one can detect with manual palpation, breast cancer fibrosis is a dynamic process that results in matrix stiffness increasing from normal ~150 to stiff 5000 Pascals (Pa) over months to years as a result of enhanced collagen expression and lysyloxidase crosslinking. I will present data on our new understanding of a molecular mechanism used by MECs interpret stiffness changes in which the EMT marker Twist changes its nuclear localization based on binding to GTPase Activating Protein (SH3 Domain) Binding Protein 2 (G3BP2). G3BP2 suppression drives tumorigenesis in mice whereas higher expression is correlated with recurrence free survival in women (Wei et al, Nature Cell Bio 2015). I will also describe our efforts to more accurately mimic the onset of tumor‐associated fibrosis using dynamic methacrylated‐hyaluronic acid (MeHA) hydrogels, whose stiffness that can be modulated from “normal” 100 Pa to “malignant” 5000 Pa, utilizing a two step polymerization process. Mammary epithelial cells cultured on 100 Pa MeHA hydrogels form and remain as polarized acini and then undergo EMT upon matrix stiffening to 5000 Pa. However, the degree of matrix stiffening and culture time prior to stiffening play a large role in acini transformation; increasing culture time on soft matrix prior to stiffening from 6 to 10 days delayed the onset malignant transformation by as much as 35%. EMT is independent of acinus size, cell density, and is not cell intrinsic, suggesting that individual acini respond to the stiffness but their epigenetic state and structure can protect a subset of acini from stiffening. These data indicates a more complex interplay of intrinsic ECM cues and acinar structure in regulating signaling that results in EMT and the onset of a malignant phenotype.Support or Funding InformationThis research was supported in part by the National Institutes of Health (DP2006460 to AJE), Department of Defense ( W81XWH‐13‐1‐013 to AJE and JY), and National Science Foundation Graduate Research Fellowship program (to MO).
Molecular Engineering for Imaging and Reprogramming in Live Cells
Authors: Wang Peter Yingxiao , Sun Jie , Lei Lei 
Published: June 2021

Signaling molecules and their activities are well coordinated in space and time to regulate cellular functions in response to mechanical and chemical microenvironment. Based on fluorescent resonance energy transfer (FRET), we have developed genetically encoded biosensors to monitor the dynamic molecular activities (such as Src and FAK activities) in live cells at subcellular compartments when cells interact with their neighbors or mechanical/chemical microenvironment. In a recent study, we show that a ubiquitous signaling protein, Src Homology2 (SH2) Domain‐containing Protein Tyrosine Phosphatase 2 (Shp2), displayed unexpected plasticity of conformational changes via intramolecular interactions within Shp2 (cis‐interaction). We found that two phosphorylated regulatory tyrosines upon stimulated phosphorylation can compete for the cis‐interaction of the same SH2 domain within Shp2 to achieve plasticity. The antagonistic combination of contextual amino acid sequence and position can create arelatively small difference between the two phosphorylated tyrosines in their overall competitiveness for intramolecular conformational regulation. Enlarging this difference by swapping the sequences at the two tyrosine positions resulted in loss of conformational plasticity and reprogrammed downstream ERK signaling dynamics. We have further engineered a machinery molecule based onShp2 which allows an integrated capability of imaging and manipulation of single cell life. We suggest that this strategy can serve as a general and basic design principle for natural and synthetic proteins, with their conformations and functions tunable to regulate downstream physiological consequences. As such, molecular engineering and biosensor development can provide powerful tools for the imaging and manipulation of cellular lives at single cell levels.Support or Funding InformationThis work is supported in part by NIHHL098472, HL109142, HL121365, NSF CBET1360341, UC San Diego.
Chemical Biology And Endomembrane Trafficking In Plants
Authors: Hicks Glenn R , Zhang Chunhua , Van de Ven Wilhelmina , Li Ruixi , Raikhel Natasha 
Published: June 2021

Endomembrane trafficking is essential for coordinated growth and development in plants and response to environment. In particular, key plasma membrane proteins such as PIN auxin transporters and the BRI1 brassinosteroid receptor translocate dynamically between the endosomes and plasma membrane. We utilized a previously published large‐scale chemical library screening approach in which we identified small molecules that inhibited pollen germination or tube growth. This tip growth requires exocytosis, endocytosis and other endomembrane trafficking processesWe then identified groups of small molecules that affect trafficking of PIN auxin transporters and other plasma membrane proteins in Arabidopsis roots. One of these compounds (ES2) targets the essential EXO70A1 component of the exocyst complex in Arabidopsis which is necessary for normal development. In Arabidopsis, there are 23 EXO70 genes (in mammals and yeast they are low copy number) where, among other roles, they appear to be involved in autophagy, cell division and pathogen responses. ES2 targets the exocyst complex in plants as well as mammals including humans where defective recycling/exocytosis have been correlated with disease. To our knowledge, ES2 is the first bioactive compound known to have this specificity. To examine exocytosis and its regulation in more detail, we have examined exo70 mutants, generated EXO70A1 structural data and are examining additional small molecules that may affect recycling/exocytosis.Support or Funding InformationAcknowledgement: This work was supported by the US Department of Energy DE‐FG02‐02ER15295 (GRH, NVR).
Vitamin B12 and Placental Expression of Transcobalamin in Pregnant Adolescents
Authors: Layden Alexander J. , O'Brien Kimberly O. , Pressman Eva K. , Kent Tera R. , Finkelstein Julia L. 
Published: June 2021

BackgroundTranscobalamin is a key placental protein involved in transport of vitamin B12 to the fetus. However, few data currently exist on the ability of the placenta to modify vitamin B12 transporter expression, particularly among high‐risk populations such as pregnant adolescents.ObjectiveThis study was conducted to determine the impact of maternal and neonatal vitamin B12 status on placental transcobalamin (TC) expression in a cohort of healthy pregnant adolescents in the United States.DesignSerum total vitamin B12 concentrations were measured from maternal blood samples at mid‐gestation (26.4 ± 2.8 weeks) and delivery (39.8 ± 1.4 weeks) and infant cord blood samples at birth. Placentas were collected at delivery and TC mRNA expression (ΔΔCt) and TC protein abundance (TC:α‐actin) were determined. Linear and binomial regression models were used to examine the associations of maternal (mid‐gestation, delivery) and infant cord blood vitamin B12 status with placental TC mRNA expression and TC protein abundance (n=63).ResultsMaternal serum vitamin B12 concentrations at mid‐gestation were not associated with placental TC mRNA expression or TC protein abundance (p>0.05). Higher maternal serum vitamin B12 concentrations at delivery were associated with higher placental TC mRNA expression (p=0.03), but not TC protein abundance (p>0.05). Higher placental TC protein abundance was also associated with higher infant cord blood vitamin B12 concentrations (p=0.003).ConclusionsHigher placental TC protein abundance was associated with higher neonatal vitamin B12 status, indicating an important role in vitamin B12 transport to the fetus.Support or Funding InformationThe United States Department of Agriculture (USDA): USDA 2005‐35200‐15218 and USDA 2010‐34324‐20769; and the Division of Nutritional Sciences, Cornell University
Maternal Choline Supplementation Influences Placental Glucose Uptake and Metabolism in a Manner Dependent on Fetal Sex
Authors: Kwan Sze Ting (Cecilia) , King Julia H , Yan Jian , Jiang Xinyin , Hutzler Jason S , Roberson Mark S , Caudill Marie A 
Published: June 2021

The placenta is responsible for delivering nutrients such as glucose to the fetus to support its growth and development, which is especially important during late gestation when fetal growth is most rapid. The ability of the placenta to efficiently provide nutrients is dependent on its vascular development and the abundance of nutrient transporters at the maternal fetal interface. Maternal choline supplementation (MCS) was shown to improve placental vasculature, but it is still unknown if MCS affects placental transporter abundance and fetal nutrient delivery. To test the hypothesis that MCS beneficially modulates placental glucose supply, pregnant mice were fed a diet containing 1, 2 or 4 times the recommended choline level. The placentas were collected at gestational day (E) 15.5 and 18.5 for evaluating the expression of key glucose transporters and enzymes involved in glycogen metabolism as well as the glycogen concentration. Data were analyzed using a mixed linear model. At E15.5, MCS reduced the membrane protein abundance of Glut1 transporter as well as the mRNA expression of the glycogen synthesizing enzyme Gys1 (p<0.05). The mRNA expression of the glycogen catabolic enzyme Pygm in the female placentas also tended to increase (p=0.08). Consistent with these findings, histological staining of placental glycogen tended to be lower (p=0.08). At E18.5, MCS had no effect on Glut1 transporter expression in either male or female placentas. However, MCS increased the membrane protein abundance of Glut3 transporter and the mRNA abundance of Gys1 in the female placentas (p<0.05). These changes resulted in a 2‐fold increase in glycogen concentration in the female placentas, as shown by histological staining and biochemical measurement (p<0.05). No such changes were seen in the male placentas at this time point. Overall, these data indicate that MCS modulates placental glucose transporter expression and glycogen metabolism in a manner highly dependent on fetal sex. We suggest that these choline‐mediated changes in placental glucose metabolism differentially influence glucose delivery to the fetus, with potential consequences on offspring development and disease risk in later life.Support or Funding InformationUSDA and Egg Nutrition Center
ACCESS AND ADOPTION OF NUTRITION SPECIFIC AND NUTRITION SENSITIVE MESSAGES IN ETHIOPIA: A QUALITATIVE GENDERED COMPARISON
Authors: Min‐Barron Marion 
Published: June 2021

The rise of multisectoralism, in conjunction with the increased interest to improve women's empowerment in the agricultural sector, has led to a dynamic and gender focused effort to improve nutrition outcomes through nutrition sensitive interventions. Questions still remain, however, on how well, at the programmatic level, nutrition education through nutrition‐sensitive platforms (such as agriculture and social safety nets) translates into adoption of nutrition‐related behavior change. This qualitative research study compares how nutrition sensitive and nutrition specific education and messaging is accessed and adopted by men and women in the Ethiopian household economy. With a sample size of 32 focus groups, 320 nutrition knowledge surveys and 10 key informant interviews, this research study was conducted in two main regions within Ethiopia, Oromia and the Southern Nations, Nationalities and People's Region (SNNPR). Focus groups participated in a unique participatory ‘Gender Box’ activity in which the group was asked to identify nutrition related behaviors and then designate them to either a female, male or ‘both male and female’ box, depending on the perceived gender of responsibility. Results indicate that nutrition specific messages (such as exclusive breastfeeding and cooking) are primarily accessed by women through the health sector but perceived by women to have be the responsibility of both the male and female. Nutrition sensitive messages (such as diversification of crop production) are generally accessed by men through the agricultural sector and media. Perceptions of responsibility for these messages vary, depending on the general nutritional knowledge of the focus group and the level of gender/women's empowerment program exposure. Perhaps most interesting, however, is the message sharing and discussion process. Nutrition specific messages accessed by women are often discussed and shared with their male spouses. Nutrition sensitive messages accessed by men, however, were rarely discussed in the home after exposure. Results from this study provide great insight into the process of nutrition message access and adoption within the household. Results also point toward perhaps a necessary shift away from individual targeted nutrition education to the provision of nutrition education to the household couple, thereby fostering and promoting discussion and message sharing between both genders.Support or Funding InformationUSAID/Save the Children International
Impact of the Shaping Healthy Choices Program on Students’ Lunchtime Fruit and Vegetable Consumption: A Randomized Controlled Trial of a Multi‐Component School‐Based Nutrition Intervention
Authors: Taylor Jennifer C , Scherr Rachel E , Linnell Jessica D , Feenstra Gail , Dharmar Madan , Zidenberg‐Cherr Sheri 
Published: June 2021

Most youth in the US do not consume recommended levels of fruits and vegetables. Multi‐component school‐based interventions are encouraged as a strategy to improve these dietary behaviors, but further evaluation of such programs is needed to assess their impact. The objective of this study was to examine the effects of the Shaping Healthy Choices Program (SHCP) on lunchtime fruit and vegetable intake, as part of a randomized controlled trial of this multicomponent nutrition education intervention. Two Northern California elementary schools were randomly assigned to control or intervention treatments. Fruit and vegetable selection, consumption, and waste from school lunches were determined at the start (fall 2012, pre‐test) and end (spring 2013, post‐test) of the implementation year using digital imaging, a plate waste method. Each fourth‐grade classroom was observed over 2–3 days within each time point. Students were included in analyses when complete fruit (n=39 control, n=72 intervention) and/or vegetable (n=39 control, n=73 intervention) data were collected on at least two days within each time point. Exact tests examined associations between school and number of students consuming no fruits and vegetables within each time point. Changes in quantities selected, consumed, and wasted were compared between schools using t‐tests and Mann‐Whitney U‐tests. Similar percentages of students consumed no vegetables at pre‐test (49% control, 47% intervention), but fewer intervention (29%) than control (72%) students consumed no vegetables at post‐test. Vegetable consumption among intervention students significantly increased relative to changes among control students (P=0.008), and percentage waste from vegetables decreased among intervention students relative to control (P=0.020). Approximately 20% of students consumed no fruit at post‐test in both schools (ns), although more intervention (26%) than control (10%) students consumed no fruit at pre‐test (P=0.052). There were no significant differences in changes in quantities of fruit selected, consumed, or wasted. Overall, the SHCP successfully improved dietary behaviors related to vegetable, but not fruit, consumption. Given the wide variability in fruit and vegetable consumption, as well as the large proportion of students consuming no vegetables, an objective for future research should be to examine other factors that may help predict these dietary behaviors and their malleability.Support or Funding InformationFunding was provided by UCANR competitive grant #11‐1018, USDA 2011‐38420‐20082, and USDA NIFA Hatch project 221082.
Dysfunction of Insulin‐like Growth Factor Signaling in Skeletal Muscles of Low Birth Weight Neonatal Pigs
Authors: Chen Ying , Zhu Haibo , McCauley Sydney R. , Oliver Katherine R. , Tinnesz Kacie A. , El‐Kadi Samer W. 
Published: June 2021

Low birth weight (LBWT) neonates experience restricted fetal muscle development and impaired postnatal muscle growth. Our previous data suggest that protein synthesis is lower while protein degradation is not different in skeletal muscle of LBWT compared to normal birth weight (NBWT) neonatal pigs. We hypothesized that decreased protein synthesis in skeletal muscle of LBWT pigs is a consequence of dysfunction of insulin‐like growth factor (IGF) signaling cascade. Twenty four LBWT and NBWT male pigs were euthanized to collect blood and longissimus dorsi (LD) muscle samples. Plasma IGF‐I concentration was measured using a commercial ELISA kit, mRNA expression by real‐time PCR and protein expression and phosphorylation by western blot. Plasma IGF‐I concentration and mRNA expression of IGF‐I and IGF binding protein 5 (IGFBP 5) were lower in LD muscle of LBWT pigs (P < 0.05). However, mRNA and protein expression of IGF‐I receptor was higher in the LD muscle of LBWT compared to NBWT pigs (P < 0.05). Protein expression of eukaryotic initiation factor 4E binding protein 1 (4EBP1) and phosphorylation of ribosomal protein S6 kinase 1 (S6K1) were lower in LD muscle of LBWT compared to their NBWT siblings (P < 0.05). These results suggest that in spite of the increased abundance of IGF‐I receptor in muscles of LBWT pigs, there is a reduction in the expression of downstream effectors of IGF‐I. As a result, IGF signaling is compromised and could contribute to impaired postnatal muscle growth in LBWT compared to NBWT neonatal pigs.Support or Funding InformationVirginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture (S.W. El‐Kadi)
Gestational Exposure to Maternal Obesity Influences β3‐Adrenergic Agonist Induced Beiging of White Adipose Tissue in Offspring
Authors: Shankar Kartik , Kang Ping , Zhong Ying , Thakali Keshari M , Wankhade Umesh D 
Published: June 2021

Maternal obesity is now recognized as an important contributing factor to the currently unfolding epidemic of obesity. In animal models, maternal obesity and exposure to high‐fat diets in utero, unequivocally predisposes the offspring to greater weight gain, metabolic dysfunction and a host of other related comorbidities, such as fatty liver disease. Our previous work in both rat and mouse models of obesity showed that offspring of obese dams are hyper‐responsive to an obesogenic challenge post‐weaning, and gain greater weight and fat mass. In part this is associated with decreased energy expenditure, impaired expression of mitochondrial OXPHOS and lipid oxidative genes and lower expression uncoupling proteins in liver, skeletal muscle and white adipose tissue. Nonetheless, the consequences of maternal obesity on programming of adipose tissue development, especially brown/beige adipose tissue development are unknown. In this report, we investigated role of maternal obesity on beige fat development in offspring following β3‐adrenergic agonist. Female C57BL6/J mice were fed diets with either low (10%) or HFD (45% of calories) for 12 wk starting at 5 wk of age. Dams were mated with males on control diets and provided access to respective diets during pregnancy and lactation. At weaning, offspring were weaned onto control and HFD, creating four groups (CC, CH, HC, HH, denoting maternal and offspring diets respectively). Male offspring from the four groups were followed till 20 wk of age. HFD‐fed offspring from HF dams (HH) gained significantly (p<0.05) greater body weights than offspring from lean dams (CH). At 20 wk of age, offspring were treated with either vehicle or β3‐adrenergic receptor agonist CL‐316,243 (1 mg/kg, ip) for one week (N=4–5 each). CL‐316,243 is a well established activator of beige adipocyte formation. Twenty weeks of diet intervention lead to significantly consistent increased weight gain in HH compared to other groups. One week of CL injection towards to end of study did not affect the weight gain. There were no significant differences in overall body weight between vehicle and CL treated animals. Gene expression analysis of inguinal adipose tissue depot (iWAT) revealed significant differences in vehicle and CL treated groups. Expression of brown‐fat specific genes such as Ucp1, Cidea and Pgc1a was affected by maternal HF diet feeding in both vehicle and CL treated group. Moreover, maternal obesity hampered the response to CL‐316,243 consistent with programming defect in adipose tissue. Further analysis of developmental aspects of beiging of adipose tissue is under investigation. Our findings indicate that maternal obesity influences beige cell formation in response to classical beiging inducers which might influence modulation of energy expenditure, metabolism and overall risk of obesity.Support or Funding InformationSupport USDA CRIS 6206‐51000‐010‐05S