bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the role of protein O‐fucosyltransferase 1 in Toll‐like receptor signaling (1004.6)
Authors: Mann Jessica , Li Ning , Laky Karen , Fraser Iain , Nita‐Lazar Aleksandra 
Published: June 2021

Protein O‐fucosyltransferase 1 (Pofut1) adds fucose to the serine or threonine residues in the consensus sequence C2‐X(4,5)‐[S/T]‐C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. The most widely studied Pofut1 substrate is Notch, and the modification is essential in many developmental events involving Notch signaling, such as the development of the nervous system, myelopoiesis and lymphopoiesis, and later T‐cell and B‐cell development. It has not been, however, previously implicated in innate immune signaling.We have identified protein O‐fucosyltransferase 1 (Pofut1) as a significant hit in a genome‐wide RNAi screen of Toll‐like receptor (TLR) signaling in mouse RAW264.7 cells, where Pofut1 knockdown led to a reduction in LPS‐induced TNF expression.To further investigate the role of Pofut1 in the TLR signaling, we are using both Pofut1 siRNA transfected RAW264.7 cells and bone marrow derived macrophages (BMDM) from Pofut1 conditional knockout mice. We have studied the TLR4 pathway upon stimulation with lipopolysaccharide, combining cytokine expression assays, protein phosphorylation and protein expression profiling using Western blotting and mass spectrometry, and protein localization experiments.Grant Funding Source: This research was supported by the Intramural Research program of NIAID, NIH.
The commensal glycoantigen PSA mitigates inflammation through a novel mechanism of T cell‐T cell interaction (1004.7)
Authors: Jones Mark , Johnson Jenny , Cobb Brian 
Published: June 2021

Asthma and airway inflammatory disease has become the leading cause for ER visits in the US, a four‐decade trend linked to the increasing sterility of western lifestyles and a proposed lack of early microbial antigen exposure. Here, we demonstrate that gastrointestinal contact with the Bacteroides fragilis glycoantigen polysaccharide A (PSA) educates the peripheral immune system to limit the degree of inflammation. Effective immune responses upon re‐exposure to an antigen is typically mediated through antigen‐experienced memory T cells, whereas regulatory T cells are known to play key roles in suppressing immune responses, generally through the secretion of immunosuppressive cytokines like IL‐10. Here, we show that gut exposure to PSA increases a population of antigen experienced CD4+CD45Rblo T cells which synergistically amplify IL‐10 production in peripheral tissues upon inflammatory stimulus. We propose a novel pathway of T cell‐crosstalk in which PSA treatment generates commensal glycoantigen experienced T cells in the gut environment that are capable of dampening the magnitude of antigen‐specific memory responses in the periphery. These findings provide a mechanistic framework for the hygiene hypothesis where communication between the microbiota in the gut and the T cell compartment links commensal products to non‐specific peripheral immune quiescence resulting in reduced susceptibility to inflammation.Grant Funding Source: Supported by: NIH DP2 (1‐DP2‐OD‐004225), NIH R01 (5‐R01‐GM082916), AAF (EEA 10‐0187), T32 (AI089474)
The long non‐coding RNA HAS2‐AS1 enhances the transcription of hyaluronan synthase 2 (1005.1)
Authors: Vigetti Davide , Deleonibus Sara , Viola Manuela , Karousou Evgenia , D'Angelo Maria Luisa , De Luca Giancarlo , Passi Alberto 
Published: June 2021

As the accumulation of the glycosaminoglycans hyaluronan (HA) into arteries wall supports cardiovascular pathologies and protein modification by attachment of beta‐N‐acetylglucosamine (GlcNAcylation) is involved in diabetic angiopahties, we studied the involvement of O‐GlcNAcylation in the regulation of HA synthesis. Here we report that the long non coding RNA HAS2‐AS1 enhances the transcription of hyaluronan synthase 2 (HAS2), the main HA synthetic enzyme in humans.We found that O‐GlcNAcylation increased both HAS2 mRNA as well as HAS2‐AS1 RNA, the natural antisense transcript of HAS2 ,which is complementary to exon 1 of HAS2. Such HAS2 mRNA increase could be reduced by the abrogation of HAS2‐AS1.Further, we found that the HAS2‐AS1 promoter was activated by O‐GlcNAcylation via NF‐kB, whereas HAS2 promoter did not respond to such glycosylation. The presence of HAS2 exon 1 to its promoter increased transcriptional activity after O‐GlcNAcylation.As it is known that long non coding RNAs modulate epigenetic modifications, we studied the chromatin conformation by nuclease accessibility assays and found that HAS2‐AS1 was critical to maintain the chromatin around HAS2 promoter in a “open” conformation.Our results indicate that HAS2 transcription is finely regulated not only simply by binding transcription factors to the promoter, but also by modulating chromatin accessibility through long non coding RNA.
Basonuclin 2 overexpression promotes keratinocyte proliferation and may contribute to basal cell carinoma tumorigenesis (1011.8)
Authors: Muller Bradley , Cornett Jonathan 
Published: June 2021

Basal cell carcinoma (BCC) is the most common form of human skin cancer. Alterations in the sonic hedgehog‐patched signaling pathway are considered necessary events in BCC progression. To identify additional driver genes in BCC tumorigenesis, we carried out a piggyBac transposon mutagenesis screen in mice. The basonuclin 2 (bnc2) gene was identified as a common insertion site in multiple independent tumors. Further analysis revealed overexpression of bnc2 mRNA in these tumors when compared with normal skin. Bnc2 is a zinc finger protein of unknown function. To gain insight into its role in normal cells, we overexpressed bnc2 in human keratinocytes. Bnc2 overexpression increases proliferation of these cells and may prevent terminal differentiation. Taken together, these results suggest that bnc2 gene may be a novel oncogene involved in the progression of basal cell carcinomas.Grant Funding Source: Supported by Lee University faculty research grant
Multiplex measurement of human kidney biomarkers in serum using the Magnetic Luminex® Performance Assay (1012.2)
Authors: Anderson Michael , Rynning Michael , Fuerstenberg Richard , Schmidt Jane 
Published: June 2021

The kidneys play an important role in organismal homeostasis by regulating osmolality and blood pressure, aiding in the reabsorption of water and nutrients, excreting wastes, and secreting hormones. Renal function is also important in the metabolism and excretion of drugs; therefore, analyzing nephrotoxicity using renal biomarkers is an important experimental step during drug development. Historically, renal function has been evaluated by measuring serum creatinine and blood urea nitrogen levels. Recently, more sensitive kidney biomarkers have been identified including TIM‐1/KIM‐1/HAVCR, Lipocalin‐2/NGAL, Osteopontin, Cystatin C, Clusterin, CXCL10/IP‐10, RBP‐4, Fetuin A/AHSG, and TFF3. Serum samples from 10 healthy individuals, 10 acute kidney injury (AKI) individuals, and 10 individuals diagnosed with renal failure were evaluated using the Human Kidney Biomarker Magnetic Luminex Performance Assay. We observed statistically significant differences in the AKI group compared to the healthy group for Lipocalin‐2, Osteopontin, Fetuin A, and Cystatin C. We observed statistically significant differences in the renal failure group compared to the healthy group for TFF3, Lipocalin‐2, Clusterin, Fetuin A and Cystatin C. We also observed statistically significant differences in the AKI group compared to the renal failure group for the following biomarkers: TFF3, Fetuin A, and Cystatin C.The Human Kidney Biomarker Magnetic Luminex Performance Assay from R&D Systems, Inc. is designed for simultaneous quantitative determination of biomarkers in serum, plasma or urine.
Profiling 200 biomarkers in cancer cell culture supernates and serum using Luminex® screening assays (1012.3)
Authors: David James , Anderson Michael , O'Brien Isabel , Schwartz Matthew , Schmidt Jane 
Published: June 2021

Cancer progression involves metabolic pathways related to cell growth and proliferation, adhesion, angiogenesis, apoptosis, and others. Multiple biomarkers in serum have been identified that are related to the presence of various cancers as well as the stage, metastatic potential and prognosis. Efforts to quantify changes in these biomarkers will enhance the understanding of the activation of cancer‐related pathways. The measurement of a single biomarker can have limited utility in such a complex disease as cancer, while multiplex profiling can lead to a better understanding of cancer biology and consequently to better diagnostic and therapeutic methods.Luminex® Screening Assays are highly flexible bead‐based multiplex assays. They allow up to 100 biomarkers, selected from a total of about 200 analytes, to be simultaneously profiled in cell culture supernates, serum or plasma samples. We measured a total of 200 analytes from a variety of cancer cell supernates and serum samples from individuals with a variety of cancers or apparently healthy individuals. The biomarkers tested included cancer antigens, cytokines, chemokines, growth factors, MMPs, protease inhibitors, and other markers. Starting with only 50 µL of each sample, we obtained quantitative results for biomarkers of cancer growth and metastasis, angiogenesis, matrix remodeling, cell adhesion, metabolic function, and cell death.
Activation of Cdc42 is critical for sustained Ca2+ oscillations stimulated by antigen crosslinking of IgE/FcεRI complexes in RBL mast cells (1013.3)
Authors: Wilkes Marcus , Baird Barbara , Holowka David 
Published: June 2021

Antigen stimulation of mast cells via FcεRI, the high‐affinity receptor for IgE, triggers a signaling cascade that requires Ca2+ mobilization for exocytosis of secretory granules during an allergic response. To characterize the role of Rho GTPases in FcεRI signaling, we utilized a mutant RBL cell line, designated B6A4C1, which is deficient in antigen‐stimulated Cdc42 activation that we showed previously to participate in these processes. To monitor Ca2+ responses in transfected cells, we co‐expressed the genetically encoded Ca2+ indicator, GCaMP3, together with mutant Rho proteins. In response to antigen, B6A4C1 cells exhibit attenuated Ca2+ oscillations that are restored to wild type RBL‐2H3 levels by expression of constitutively active Cdc42 G12V or a GEF for Cdc42, DOCK7. The capacity of Cdc42 G12V to reconstitute this response is lost when the conserved di‐arginine motif located at the C‐terminus of Cdc42 is mutated to di‐glutamine. To investigate the signaling step that is most directly activated by Cdc42 in this process, we evaluated its role in stimulated IgE receptor endocytosis, a Ca2+‐independent process that is defective in B6A4C1 cells. We find that Cdc42 G12V reconstitutes this response, implicating the importance of Cdc42 in a step upstream of phospholipase Cγ activation in Ca2+ responses, possibly in stimulated synthesis of phosphatidylinositol 4,5‐bisphosphate.Grant Funding Source: National Institute of Allergy and Infectious Diseases Grant R01AI022449
A village health worker‐led intervention to promote and support exclusive breastfeeding in rural Zimbabwe is feasible, acceptable and effective (1015.8)
Authors: Matare Cynthia , Mbuya Mduduzi , Stoltzfus Rebecca , Dickin Katherine , Humphrey Jean 
Published: June 2021

Exclusive breastfeeding (EBF) is a pillar of child survival but in Zimbabwe, less than 6% of infants are exclusively breastfed for 6 mo. Peer counseling has been shown to improve rates of EBF.We pilot‐tested a Village Health Worker (VHW)‐based EBF education intervention and assessed acceptability, within‐household reach, motivators triggered, learning outcomes, and EBF intentions and behavior. The intervention delivered key messages at four times: late gestation, and <1 wk, 1 mo, and 3 mo post‐partum.Nurses trained 20 VHWs on the EBF intervention over 4.5 days. The modules were delivered to 43 women; 13, 5, 11 and 14 at the respective time points, above. Researchers conducted a knowledge survey before the VHW visit and semi‐structured in‐depth interviews with the mothers 1 wk after the visit. The interviews were translated into English, transcribed and analyzed using thematic analysis.The intervention was acceptable and directly or indirectly reached other influential household members who shape infant feeding practices. The intervention improved EBF knowledge and led to changes in infant feeding behaviors and intentions, motivated mostly by desire for a healthy baby. Some mislearning around maternal diet determining breastmilk production also occurred.We conclude that targeted messages within home‐based education modules delivered by VHWs to promote EBF are promising and should be tested at scale.Grant Funding Source: Supported by the Bill and Melinda Gates Foundation (OPP1021542) and DFID, UK
Semi‐automated detection of milk duct dilatation recorded by ultrasound (1016.5)
Authors: Geddes Donna , Fiorentino Jamie , Keating Adrian 
Published: June 2021

In lactating women milk is stored predominantly in the alveoli of the breast and is made available to the infant or the breast pump by milk ejection. During breastfeeding or breast expression milk ejection can be detected by visualization of duct dilation and milk flow with ultrasound imaging. Currently, analysis of the ultrasound video is performed manually, is time consuming and subject to error. This pilot study tested an algorithm which determined the average intensity within a region of the video across all video frames, with the aim of determining if changes in this averaged intensity within the duct corresponded with milk flow. The region of milk flow was identified visually from the ultrasound, which detected the movement of high intensity flecks within the milk. Ultrasound intensity within a duct was measured in 7 ultrasound videos. Intensity was also measured in an area of skin and subcutaneous fat for comparison, as no correlation with milk flow is expected in these regions. Percentage changes in intensity (mean (range)) were 22% (11‐37%), 21% (14‐27%) and 112% (60‐251%) for skin, subcutaneous fat and ducts respectively. The increase in intensity at the beginning of milk ejection was 83% (60‐140%). Preliminary results suggest that targeted measurement of ultrasound intensity may be useful in accurately measuring the timing of milk ejection.Grant Funding Source: Medela AG
Yogurt intake is associated with a healthier dietary pattern and is a lower contributor of energy intake in obese individuals (1018.6)
Authors: Cormier Hubert , Thifault Elisabeth , Garneau Veronique , Tremblay Angelo , Drapeau Vicky , Perusse Louis , Vohl Marie‐Claude 
Published: June 2021

Objectives: To examine whether yogurt consumption is associated with Prudent or Western dietary patterns and to study associations between total, fat‐free, low‐fat (2% M.F.) yogurt intake and obesity. Methods: A 91‐items food frequency questionnaire was administered to 664 subjects from the INFOGENE study. Obesity was defined as having a body mass index > 30kg/m². A total of 564 subjects (160 obese and 404 non‐obese individuals) consumed yogurt and were then classified as “consumers”. Results: Yogurt consumption (daily servings) was positively associated to the Prudent dietary pattern (r=0.15, p=0.0001) and inversely associated to the Western dietary pattern (r=‐0.22, p<0.0001). In yogurt consumers, yogurt contributed to a lesser extent to daily energy intake in obese than in non‐obese individuals (% of total energy, 2.92±2.53% vs. 3.54±2.49% respectively, p=0.02). In addition, non‐obese subjects reported more daily servings of high‐fat yogurt compared to obese individuals (0.18±0.40 vs. 0.10±0.23, p=0.03). Conclusions: This study shows that yogurt consumption is associated with a healthier dietary pattern. Moreover, the contribution of yogurt to daily energy intake is more pronounced in non‐obese individuals.Grant Funding Source: Danone Nutricia Research, Centre Daniel Carasso
The influence of community food environment on weight status of young children participating in the Children's Healthy Living Program in Guam (1019.1)
Authors: Matanane Lenora , Li Fenfang , Leon Guerrero Rachael , Acosta Mark , Barber Robert , Fialkowski Marie 
Published: June 2021

Many studies support the influential role that the community food environment (CFE) has on children’s weight status. The purpose of this study is to determine if the CFE is associated with early childhood body mass index (BMI) in 3 communities on Guam. CFE factors, including fruit/vegetable availability, store advertising, and community readiness (CR) for change, were assessed using tools amended for the Children’s Healthy Living (CHL) Program community randomized trial. Anthropometry data of children (2 to 8 years; n=536) were collected across all communities and BMI z‐scores calculated using the 2000 CDC growth curves. Mean differences between BMI z‐score and CFE factors were examined using a general linear model and Spearman correlations evaluated associations. A total of 42 stores were surveyed of which a majority were small markets (74%) and the remaining were convenience stores (17%) and large grocery stores/supermarkets (9%). At the community level, there was a significant difference in mean BMI z‐score (p<0.001); among the CFE factors, the only significant difference was in CR score (p<0.05). A significant negative correlation was found only between mean BMI z‐score and CR score (r=‐0.31, p=0.04). High density of small markets may be an opportunity for CFE intervention but further investigation on CFE elements, including CR, with more communities is needed to understand the CFE’s influence on Guam.Grant Funding Source: Supported by Agriculture and Food Research Initiative Grant no. 2011‐68001‐30335 from the USDA NIFA.
Current practices and strategies to improve the food environment in low‐income schools to reduce non‐communicable risk factors in children in Guatemala City: a qualitative study (1019.21)
Authors: Pehlke Elisa , Letona Paola , Gittelsohn Joel 
Published: June 2021

Developing countries like Guatemala have recently undergone rapid transitions driven by globalization and development. These have accelerated the increase in prevalence of overweight, obesity and non‐communicable disease risk factors among children. Schools have been identified as effective settings for early intervention and favorable arenas in which to target children’s dietary behaviors, especially through structural approaches. The pilot phase of ¡Pilas!, a school‐based intervention developed by the Institute of Nutrition of Central America and Panama (INCAP), with the support of Johns Hopkins University, sought to improve children’s nutrition but was unsuccessful in its objective to facilitate positive change in school food kiosks (casetas). The aim of this qualitative study is to better understand influencing factors on nutrition within the context of low‐income elementary schools in Guatemala City and to improve the school food environment by identifying strategies targeted at casetas. In‐depth interviews with school principals (n=4) and food vendors (n=4) and focus groups involving interactive activities with children (n=48) were conducted. The current food environment is shaped by school and government regulations and enforcement, products available at casetas, food and/or money brought from home and school provided snack (refacción). Other determinants of dietary behavior include children’s preferences, product pricing, and parental time and concern for nutrition. The degree to which regulations are understood and enforced at each school, as well as evident vendor challenges, are necessary to consider in identifying appropriate intervention level and design. Hopeful strategies to be further piloted include enforcement policies, healthy and creative food preparation, price manipulation and promotions, raffles and games, as well as government and big company involvement.Grant Funding Source: Institute of Nutrition of Central America and Panama (INCAP)
Listeriosis: how concerned should a pregnant woman be? (1019.27)
Authors: Fahnestock Lindsay , Gill Gagandeep , Randhawa Manjit , Soret Samuel , Rizzo Nico 
Published: June 2021

Background: Every year, at least one major Listeria monocytogenes (Listeria) outbreak occurs within the United States. If pregnant women are uninformed of possible ramifications of contracting Listeria, the mother and child are at risk for health complications. One possibly effective communication approach to this population regarding prevention and risk is through Listeria Educational Materials (LEM). In order to ascertain the status and effectiveness of currently available LEM for pregnant women, a systematic literature review was conducted.Methods: Literature searches were conducted using widely accepted public/private databases. The mesh terms used included “Listeria pregnancy”, “listeria education”, “Listeriosis”, “Listeria pregnancy prevalence” “Listeria monocytogenes”. Only articles published within the past 10 years pertaining to educational materials for pregnant women were evaluated. Articles relating to general information of Listeria, were also narrowed to specific characteristics, traits, and origin for exposure. References to Listeria in elderly and immunocompromised individuals were excluded.Results: 4 studies involving Listeria interventions including LEM for pregnant women were identified. These studies all concluded a majority of pregnant women were still not provided with sufficient information on infection prevention of Listeria. Most educational materials provided to the women were in the form of pamphlets, and the majority of pregnant women who had heard of Listeria gathered the information through their own research efforts.Conclusions: The current evaluation of the available studies concludes there is inadequate emphasis placed on educational interventions for pregnant women regarding Listeria risk. These interventions concluded more must be done to inform these pregnant women of the dangers of Listeria as well as on the high‐risk foods they consume on a daily basis.
The Nutrition Environment Measurement Survey‐Stores in Guatemala: measurement performance between the standard (USA) and a modified version (1019.7)
Authors: Kanter Rebecca , Alvey Jeniece , Fuentes Déborah , Garcia Rosario , Bearup Richelle , Koeppel Leah , Caplan Emily , Chang Fabian , Chomitz Benjamin , Solomons Noel W. 
Published: June 2021

Background: The nutrition environment measures survey for stores (NEMS‐S) is a way to assess the consumer nutrition environment, which affects individual dietary intake. While NEMS‐S has high validity in the United States, its validity has not been tested in Guatemala. The standard US NEMS‐S was tested, modified and re‐tested in urban Quetzaltenango, Guatemala.Objective: To compare the measurement performance between the standard NEMS‐S (USA) and the modified NEMS‐S (Guatemala), respectively.Methods: Seven trained raters tested the modified NEMS‐S in 3 supermarkets, and returned one week later at the same time. Inter‐rater and test‐retest reliability were assessed using percent agreement and Cohen’s kappa. Measurement validity was based on how well each item was found based on the modified NEMS‐S. The reliability and validity of the modified NEMS‐S were compared to the standard NEMS‐S.Results: Both the inter‐rater and test‐retest reliability were very high (Cohen’s kappa >0.78) and similar to the standard NEMS‐S. The validity of many standard NEMS‐S items improved in the modified NEMS‐S, especially lean meat, milk, hot dogs, and diet soda.Conclusions: The modified NEMS‐S has a better measurement performance as compared to the standard NEMS‐S. Therefore, the modified NEMS‐S is a reliable and valid tool that can be used to measure the nutrient environment in Quetzaltenango, Guatemala.