bluuebunny/crossref_metadata_2025 huggingface dataset:
A network approach to understanding drug resistance (235.2)
Authors: Pe'er Dana
Published: June 2021

New drugs that target MAPK‐activated melanomas show good clinical results, but with varied outcomes, both in vitro and in patients. The reasons for the phenotypic heterogeneity are still unknown. Here we aim at explaining the phenotypic variability by integrating data of different types to infer network state and rewiring. We focus at the heterogeneous response of melanoma to MAPK pathway inhibition. First, we use pre‐ and post‐MAPK inhibition transcription data to identify downstream targets and pathways that interact with the MAPK pathway. We show that the network is vastly rewired in different melanoma cell lines. For example, we show that most downstream targets of the MAPK pathway are context‐specific ‐ under the control of the pathway in a subset of cell lines. We then use other data types, such as DNA copy number, epigenetics and mutations to explain the network rewiring and to link genotype to phenotype. Using our approach, we identify new vulnerabilities that can be targeted to enhance the phenotypic response to MAPK inhibition. We experimental confirm several treatment combinations and show that the cytotoxic response to MAPK inhibition can be enhanced by different drugs in different cell lines. Our analysis demonstrates the value of system‐wide perturbation data in predicting drug response in the era of personalized medicine.
Sculpting the chromatin landscape: a role for nuclear pore complexes in gene silencing (238.2)
Authors: Wozniak Richard
Published: June 2021

While the most established function of the nuclear pore complex (NPC) is the regulation of nucleocytoplasmic transport, other functions for this structure have long been proposed, including roles in defining the structure of chromatin and controlling gene expression. NPCs interact with heterochromatin and euchromatin. We hypothesize that different regions of the NPC establish distinct platforms that recruit specific chromatin interacting proteins capable of facilitating transcription, silencing, or boundaries between these chromatin states. We have established the yeast NPC protein, Nup170p, as a platform for facilitating gene silencing. Nup170p interacts with specific regions of the genome containing ribosomal protein and subtelomeric genes. Here it functions in nucleosome positioning and as a repressor of transcription. We show that the role of Nup170p in subtelomeric gene silencing is linked to its association with the RSC chromatin‐remodeling complex and the silencing factor Sir4p, and that the binding of Nup170p and Sir4p to subtelomeric chromatin is cooperative and necessary for the association of telomeres with the nuclear envelope. Our results establish the NPC as an active participant in silencing and the formation of peripheral heterochromatin.
Caretakers receiving SNAP are responsive to education to reduce preschool child sugar‐sweetened beverage consumption (252.8)
Authors: Ferris Ann , Wakefield Dorothy , Lora Karina , Quesada Catalina
Published: June 2021

A RCT, directed at low‐income parents at early childcare centers, evaluated whether an 8‐week brief intervention using the information‐motivation‐behavior theoretical framework would decrease the children’s home SSB consumption. The control group received a sham home food safety curriculum. Caretakers of 364 children completed the study, 357 of whom completed a 2‐day (weekend) food record for the child and provided information on child beverage consumption by use of an inventory of beverages in the home (HBI) at baseline and 6 months later. Fourteen percent did not consume SSB at either time point. Consumption estimates from food records and HBI among consumers were significantly correlated (r=0.32, p<0.0001). Baseline SSB consumption by either measure did not differ between intervention and control groups. Children who consumed SSBs did not change consumption over the course of the study. In contrast, children in families receiving SNAP benefits (45%) did reduce consumption over the course of the study (p=0.02) whether measured by diet records (kcal from SSB/d median (min, max), intervention: ‐9.8 [‐262, 336], control: 29.7 [‐421, 290]) or the home beverage inventory ((kcal from SSB/d ‐intervention: 0.0 [‐58, 32], control: 2.6 [‐55, 26]). SNAP recipients are responsive to reducing preschool child SSB consumption after participating in eight short interactive sessions.

Grant Funding Source: USDA/NRI 2008‐55215‐19071
Tea flavonoids stimulate mineralization in osteoblast‐like cells (259.7)
Authors: Nash Leslie , Ward Wendy
Published: June 2021

Epidemiological studies suggest that habitual tea consumption is associated with higher bone mineral density. Rooibos tea, in particular, is a rich source of flavonoids, including rutin, orientin, hyperoside, and luteolin, that may favorably modulate cellular processes such as hydroxyapatite production. The study objective was to determine if individual flavonoids (0.001µM‐100µM) promoted mineralization in Saos2 cells. Mineralization was quantified by alizarin red staining at day 21, while alkaline phosphatase activity, a marker of osteoblast cell activity, was determined at days 3, 7 and 10. Rutin (25µM), orientin (0.01µM), hyperoside (5µM) and luteolin (5µM) resulted in higher (p<0.05) mineral production than control. Higher mineral production was associated with higher alkaline phosphatase activity (p<0.05) for rutin (25µM), orientin (0.1µM), hyperoside (1µM) and luteolin (1µM) as early as 3 days into the mineralization process. Maximum enzyme activity was dependent on the flavonoid. Mitochondrial activity, a marker of cellular proliferation, reflected the mineralization data. In conclusion, flavonoids can positively influence mineral production in osteoblasts and this is, in part, due to higher osteoblast activity. Thus, tea flavonoids are a promising area for future research investigating dietary approaches for bone health.

Grant Funding Source: Supported by a NSERC Discovery Grant for W. Ward
Lipodomic analysis reveals that gamma‐tocotrienol exerts anticancer effects by inhibition of dihydroceramide desaturase and activation of sphingomyelin hydrolysis (260.6)
Authors: Jang Yumi , Jiang Qing
Published: June 2021

Our previous studies suggest that gamma‐tocotrienol (γTE), a vitamin E form rich in palm oil, has potent anticancer activities in cancer cells via modulation of sphingolipid metabolism. Here employing liquid chromatography tandem mass spectrometry, we investigated temporal changes of sphingolipid by γTE treatment in human colon cancer HCT‐116 cells. Incubation with γTE for 2 h resulted in accumulation of dihydrosphingosine and dihydroceramides (dhCer), and these changes intensified during prolonged treatment. In contrast, γTE treatment led to significant decrease in C16:0‐ceramide (Cer) from 2 to 8 h, but showed no difference at 16 h or increase at 24 h, compared with controls. Meanwhile, γTE led to decrease in C24:1‐Cer and C24:0‐Cer from 6 to 24 h, but increase in C18:0‐Cer from 16 h. Interestingly, sphingomyelins (SM) declined from 8 h but cells showed obvious apoptosis (PARP cleavage) or autophagy (LC3 increase) only at 16 h or longer treatment with γTE. With 13C3, 15N‐labeled L‐serine, we further evaluated the effect of γTE on de novo sphingolipid. We observed that γTE had no effect on total de novo sphingolipid biosynthesis, while induced increases in labeled dhCer, dhSM and SM, but decreases in labeled Cers and sphingosine, during 2‐6 h. These data indicate that γTE may inhibit dhCer desaturase (DEGS). Consistently, γTE inhibited the DEGS activity as indicated in situ and in vitro assays. Moreover, the decrease in endogenous SM without affecting de novo SM suggests that SM hydrolysis likely occurred. Studies are undertaken to evaluate the role of SM hydrolysis in γTE‐induced anticancer effects. These results indicate that γTE modulates enzyme activities in sphingolipid metabolism, which play roles in regulating cell death.

Grant Funding Source: Supported by grants R21 CA152588 and R01AT006882 from National Institutes of Health
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
Study skills in anatomy and physiology: What’s the difference? (336.3)
Authors: Husmann Polly , Barger J. Bradley
Published: June 2021

Many factors influence the way individual students learn and study, including but not limited to: pre‐existing knowledge (Bransford et al., 1999), metacognition (Gurung & Schwarz, 2009), learning and personality styles (Fleming 1992, Myers 1962), etc. This research asks the question, “Do individual students study differently for different classes?” Study skills surveys were given to medical students at the Indiana University, Bloomington campus and the West Virginia School of Osteopathic Medicine. Each student received a study skills survey near the end of their anatomy course and another survey near the end of their physiology course. These surveys included Likert scale and open‐ended questions about study habits and basic demographic information. The responses to these survey questions were then correlated with each student’s final grades in the courses. The two surveys (anatomy & physiology) from an individual were also compared to see if each student used different study habits in anatomy than physiology. Results showed that students who changed their study habits between the two classes had significantly lower anatomy grades (p<.02) than students who used similar study habits for both classes. Additional analyses were run to investigate what changes students were making and hypotheses were posited as to why changing study habits may correspond with lower anatomy grades.
The scourge of neuroanatomical nomenclature: use of neuroanatomical ontologies within the Neuroscience Information Framework (338.2)
Authors: Martone Maryanne
Published: June 2021

The brain is perhaps unique among major organ systems in the multiplicity of naming schemes for its major and minor regions. It has been divided based on topology of major features, cyto‐ and myelo‐architecture, developmental boundaries, supposed evolutionary origins, histochemistry, gene expression and functional criteria. The gross anatomy of the brain reflects the underlying networks only superficially, and thus any parcellation reflects a somewhat arbitrary division based on one or more of these criteria. A core aim of the Neuroscience Information Framework (http://neuinfo.org) is to establish a semantic framework for searching and integrating across data contained in diverse information systems. As anatomy is foundational to a common understanding of the brain, NIF and several other foundational projects, e.g., Neuronames, have worked to establish the means to translate among these different nomenclatures. In this presentation, I will discuss strategies employed by NIF, in collaboration with the International Neuroinformatics Coorindating Facility (INCF) to establish semantic interoperability of brain regions through atlasing and ontologies. I will show how these ontologies are used within the NIF to help with cross‐query of distributed data and literature and discuss the use of our semantic Wiki, Neurolex (http:/neurolex.org) as a platform for communities to contribute their nomenclatures.
Regulation of oligodendrocyte differentiation and CNS myelination by a novel transmembrane transcription factor (345.4)
Authors: Emery Ben , Bujalka H. , Koenning M. , Jackson S. , Perreau V.
Published: June 2021

Oligodendrocyte differentiation and the myelination of axons are crucial steps during vertebrate CNS development, allowing for the rapid saltatory conduction of action potentials. We previously identified a putative transcription factor, Myelin Regulatory Factor (Myrf, previously known as MRF and GM98), that is vital for oligodendrocyte differentiation and the production of CNS myelin during development. It has been controversial, however, whether Myrf directly regulates transcription, with reports of a transmembrane domain and lack of nuclear localization. Here, we find that that Myrf is a membrane‐associated transcription factor that, like Notch and the SREBPs, undergoes an activating proteolytic cleavage event to separate its transmembrane domain from the nuclear‐targeted N‐terminal region. Using ChIP‐Seq in oligodendrocytes we show that the N‐terminal cleavage product directly binds DNA, with Myrf binding sites strongly clustered around myelin genes. Luciferase assays confirm that these bound regions act as Myrf‐responsive enhancer regions. These findings identify Myrf as a novel transmembrane transcription factor, reconciling previous questions regarding its subcellular localization. We are currently investigating the expression and role of Myrf in human demyelinating disease and its animal models.
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.
Correlation between conformational dynamics and activity in protein kinase A (354.1)
Authors: Veglia Gianluigi
Published: June 2021

Protein kinases mediate a myriad of cell signaling events. Protein kinase A (PKA) is considered the prototypical kinase, sharing its catalytic core (PKA‐C) with many other kinases. Using NMR spectroscopy, we mapped the conformational energy landscape of the kinase. Although incomplete, this study unveils the activation and deactivation processes for this enzyme. We found that conformational dynamics of both backbone and side chains play a critical role in activation and regulation. In particular, backbone conformational dynamics in the slow time scale of NMR are synchronous to the enzyme turnover. While the apo state is dynamically uncommitted, nucleotide defines a dynamically committed state. The binding of inhibitors quench the enzyme’s conformational dynamics, selecting a dynamically quenched state. We also found that enhanced motions via mutations reduce the catalytic efficiency of the kinase. We conclude that the conformational dynamics of the enzyme is linked to the overall turnover, and an increase or decrease of these motions has negative effects on the catalytic cycle.
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.
Regulation of iron acquisition and storage in yeast (360.1)
Authors: Kaplan Jerry
Published: June 2021

Iron is a required element for all eukaryotes, as the facile ability of iron to gain and loose electrons permits it to participate in a wide variety of oxidation‐reduction reactions. Iron can also donate electrons to oxygen or hydrogen peroxide resulting in the generation of toxic oxygen radicals such as, superoxide anion or hydroxyl radical. Organisms therefore tightly regulate cytosolic iron concentration through regulation of iron acquisition and storage. The budding yeast Saccharomyces cerevisiae has developed mechanisms to coordinate iron storage with iron acquisition. Under iron scarce conditions the transcriptional regulators Aft/2 induces the expression of a suite of genes that encode proteins involved in iron acquisition and utilization. Under iron sufficient conditions Aft1/2 regulated genes are no longer transcribed and a different transcription factor Yap5 induces a set of genes including CCC1, which encodes a vacuolar iron importer. Import of iron into the vacuole reduces cytosolic iron levels. Coordination of the products of these transcription factors is regulated by both transcriptional and post‐transcriptional mechanisms. Most notably, the high and low iron sensitive transcription factors both respond to the mitochondrial production of iron‐sulfur clusters. While there are differences in the molecules responsible for cytosolic iron regulation, coordination of iron acquisition and storage is a consistent finding in all species.
Protein evolution – a reconstructive approach (363.2)
Authors: Tawfik Dan
Published: June 2021

Our studies aim at understanding how proteins, and enzymes in particular, evolve ‐ how does an exiting sequence with a given structure and function, change, gradually, via one mutation at a time, to give new sequences with different properties? I will describe how biological messiness ‐ noise, infidelity and inaccuracy at all levels, from single molecules to whole organisms, underlines the origins of evolutionary innovations. I will discuss several examples ranging from the functional and structural promiscuity of proteins to translational and transcription errors. I will thus show how innovation, the emergence of new protein functions and traits, begins with latent, coincidental errors that become beneficial and selectable at some point.
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.
Temporal resolution of protein signaling (473.1)
Authors: Anderson Karen , Sohl Christal , Luo BeiBei , Mo Shunyan , Kim Youngjoo , Apetri Mihaela , Lew Erin , Furdui Cristina , Schlessinger Joseph
Published: June 2021

Receptor tyrosine kinases (RTKs) play an essential role by initiating multiple signaling pathways. Given their role in cellular processes such as cell proliferation, differentiation and migration, altered RTK activity has been associated with multiple developmental disorders and cancers. Early events in the initiation of a signaling pathway involve ligand binding, receptor dimerization, and autophosphorylation of specific tyrosine residues that in turn serve as binding sites for downstream signaling molecules. Dynamic control of multiple phosphorylation modifications of a single RTK can manifest critical control on multiple signal transduction pathways. An understanding of molecular mechanisms of these early dynamic events may hold the key to understanding and predicting the nature of oncogenic behavior and predicting the affects of RTK targeted therapy. Profiling using an integrated platform of technologies including electrospray ionization mass spectrometry (ESI‐MS) revealed a discrete, ordered pattern of tyrosine autophosphorylation with normal protein signaling. However this preferential order was lost with mutant forms of RTKs associated with oncogenesis. These molecular signatures provide a new understanding of the differences between normal and oncogenic forms of RTKs and an expanded functional understanding of the emerging therapeutic class of targeted kinase inhibitors.
Understanding base lesion DNA repair (477.2)
Authors: Wilson Samuel
Published: June 2021

The mammalian DNA repair pathway for small base lesions involves excision of the damaged base, DNA synthesis to fill the excision gap and gap‐trimming steps to prepare substrates for downstream enzymes, including DNA ligases. The topic of DNA base excision repair (BER) will be reviewed, along with the hypothesis of “substrate‐channeling” of repair intermediates from one step to the next step until the repair process has been completed. The accessory proteins XRCC1 and PARP‐1 play important roles in BER, and these proteins and the BER enzymes appear to function in large macromolecular complexes. In the case of PARP‐1, poly(ADP‐ribose) adduction of itself and other BER enzymes facilitates recruitment to the repair complex. The catalytic cycle of DNA polymerase beta is relevant to the substrate‐channeling hypothesis because the enzyme plays a central role in BER. Crystal structures of human DNA polymerase beta will be discussed in the context of the catalytic cycle of polymerase beta and the substrate‐channeling hypothesis.
Student use of pictures on text‐based examination questions in an undergraduate human anatomy course (530.6)
Authors: Notebaert Andrew
Published: June 2021

A retrospective analysis was done on an undergraduate human anatomy multiple choice exam to survey the student use of printed pictures on that exam. The exam was composed of 45 multiple‐choice questions which students had one hour to complete. Seven of the 45 questions contained a visual aid designed to help students with that particular question but was not necessary to answer the given question. Of the 203 exam papers analyzed, 111 students (54.7%) used one of the included pictures which was determined by visual inspection of marks on the picture. Any mark that was determined to have been a meaningful attempt to assist in answering the question as determined by the investigator was counted for this analysis. Frequency counts were tabulated for each question on the basis of two categories; if the student marked on a question and if the student got that answer correct. Chi‐square tests were conducted to see if there were any significant differences in the frequencies between use of the picture and getting the answer correct. Out of the seven analyzed questions, only one question demonstrated a significant difference (p蠄.05). For the students that did not mark on the picture for this question, 37 out of 140 (26.4%) got the question correct while 29 out of 63 (46.0%) marked on the picture and got the question correct. The initial results indicate that a student’s use of an included visual aid had little bearing on getting that particular question correct. Because of the nature of this analysis, it cannot be determined whether the students found the pictures helpful. Instructors could use this type of analysis to identify visual aids that are either not used by the students or maybe have a negative effect on the students answer choice.
Discussion‐based advanced physiology course effectively engages students and develops higher order skills (531.16)
Authors: Hopper Mari
Published: June 2021

A discussion based advanced physiology course was developed aiming to share new discoveries and develop higher order thinking and communication skills. A three hour course with pre‐requisite animal physiology and cell biology enrolled 15 students. Students were introduced to the process and merits of discussion method. Students identified their personal discussion style and reflected on effective means of interaction. Daily “warm up” activities provided practice. Topic based readings were assigned weekly and discussion leaders and note takers were designated. Discussion leaders posed questions and engaged participants. A rubric provided feedback. Notes were posted to a Wiki and students were required to post additional comments. Other activities included critical analysis of a documentary film, case studies, and group exams. Comparison of Global Index scores from student evaluations revealed the discussion based course scored higher than a traditional physiology course offered on the same campus by the same instructor (GI 4.74 vs 4.40; 5.0 scale). Student comments included: “This course should be strongly recommended, if not required, for science majors looking to take their education to the next level.” A validated student engagement instrument (Ahlfeldt 2005) indicated engagement was significantly higher in the discussion based course with students evaluating and thinking critically more often.
Viewing video tutors improved student outcomes in anatomy and physiology (531.2)
Authors: Halpin Patricia , Lockwood M. Katherine
Published: June 2021

The purpose of this study was to determine if viewing video tutors on five specific anatomy & physiology topics would improve students’ outcomes. Two sections of anatomy & physiology were assigned video tutors from the Mastering A&P website including: movement across cell membranes, the neuromuscular junction, muscle contraction, resting membrane potential and action potential generation. Each section was taught by the same professor with the same material covered and same assignments given to the classes. In section #1, 271 students were assigned the video tutors and 172 students viewed the videos or 63% of the class. In section #2, 254 students were assigned the video tutors and 161 viewed the videos (63%). Of the students who watched the videos their mean final grade in the class was 82.39 compared to the students who did not watch the videos 74.07 (section #1), 82.8 vs. 76.4 (section #2). Questions on the video tutor topics were added to the final cumulative exam. For the students who viewed the videos their grades were higher on these specific exam questions as well 86.34 vs. 69.20 (section #1), 87.64 vs. 65.78 (section #2). Students who viewed the video had higher grades on their final cumulative exam as well 84.5 vs. 75.91 (section #1) 86.26 vs. 73.2 (section #2). In conclusion assigning video tutors improved student grades for those who watched the videos. They will continue to be assigned to classes in the future.
Understanding the neuronal controls behind heart rate and respiration (531.8)
Authors: Anjur Sowmya
Published: June 2021

Students at the Illinois Mathematics and Science Academy in Aurora have the advantage of belonging to a school which serves as a teaching laboratory that encourages creative learning. Students in the course Physiology and Disease learn physiology by designing, executing and evaluating their own experiments based on evidence. Although students are able to understand the basic principles behind heart rate and respiration, they sometimes have trouble understanding why these parameters are correlated. This semester, in order to understand better the concept of neuronal controls for these parameters, students designed laboratory experiments that involved the use of the same type of exercise to increase both heart rate and respiration rate. Heart rate was measured manually using the palpation method of the carotid artery. Respiration rate was measured using lung volume bags (Ward’s Science Item numbers 145051, 145068). Students used quantitative data from these experiments to make conclusions regarding the correlation of heart rate and respiration rate. This was followed by student research into the neuronal controls in the brain that were responsible for these correlations and subsequent presentations wherein students articulated their understanding to their peers. Student surveys concluded that hands on experimentation helped them understand the neuronal controls behind respiration and heart rate better than just studying from their textbooks or listening to lectures.
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.
Post‐dissection assessment tests: an effective intervention for improving student performance on gross anatomy practical exams (533.3)
Authors: Kirera Francis , Royer Danielle
Published: June 2021

The impact of formative assessment on medical student performance in gross anatomy practical exams was evaluated based on the post‐dissection assessment tests (p‐DAT). First year medical students at Ross University School of Medicine were provided with about 10‐post dissection questions on tagged structures based on dissection images. To determine if p‐DAT intervention had an effect on the student preparedness and test taking skills, two types of data were generated: 1) students completed an anonymous online survey of their expectations, attitudes and preferences, and 2) statistical comparisons were made between the course blocks with p‐DAT intervention versus those without the intervention. Over 70% of the responders agreed that p‐DATs were a useful learning tool, with over 80% stating that they preferred p‐DATs for all the labs. Survey responses highlight the role of this tool in helping students connect the dissections to the lecture material. There was significant improvement in student lab exam mean scores in a block with p‐DAT intervention compared to a block without intervention (67.06% to 76.64%, p<0.001). Based on our study, p‐DAT was an effective intervention for improvements in mastery of content and test‐taking strategies for gross anatomy.