bluuebunny/crossref_metadata_2025 huggingface dataset:
IUGR disrupts the PPARγ‐Setd8‐H4K20me1 loop in male rat adipose tissue (577.5)
Authors: Riddle E , Zou C.J. , Trevenzoli I , Joss‐Moore L
Published: June 2021

Intrauterine growth restriction (IUGR) programs adipose dysfunction. Appropriate adipose function is, in part, maintained by the peroxisome proliferator activated receptor gamma (PPARγ)‐Setd8‐H4K20me1 (histone 4, lysine 20, methylation) positive feedback loop. This loop relies on PPARγ’s direct transcriptional control of Setd8, as well as Setd8’s placement of H4K20me1 on PPARγ. We previously showed that IUGR causes adipose dysfunction and increases total PPARγ mRNA levels in male rat adipose tissue. However, the effect of IUGR on the PPARγ‐Setd8‐H4K20me1 loop in male rat adipose tissue is unknown.

We hypothesize that IUGR disrupts the PPARγ‐Setd8‐H4K20me1 loop in male rat adipose tissue.

IUGR was induced by bilateral uterine artery ligation in rat dams at E19 of gestation. Subcutaneous adipose tissue of male IUGR and control rats was assessed at postnatal day 21 (n=4 per group). PPARγ1, PPARγ2, and Setd8 mRNA levels were measured using real‐time PCR. Chromatin immunoprecipitation was used to quantify H4K20me1 at Promoter 1 (P1), P2 and the 3’UTR of the PPARγ gene.

Results are IUGR as % of Control ± SEM, *p<0.05. IUGR increased PPARγ1 (227 ± 40*), PPARγ2 (195 ± 29*), and Setd8 (171 ± 28*) mRNA levels in male rat adipose tissue. IUGR decreased H4K20me1 at P1 of the PPARγ gene (44 ± 6*), with no significant changes at P2 or the 3’UTR.

The PPARγ‐Setd8‐H4K20me1 loop plays an important role in adipose function and is disrupted by IUGR. Increased PPARγ and Setd8 mRNA in conjunction with decreased H4K20Me1 at PPARγ P1, suggests dysregulation of H4K20me1 placement or H4K20 demethylation. Our ongoing studies examine regulation of H4K20me1 placement on PPARγ as well as the function of the H4K20 demethylase, PHF8.

Grant Funding Source: Supported by NIH grant DK084036(LJM)
Cigarette smoke increases PAF accumulation, cell motility and EMT in triple negative breast cancer cells (58.8)
Authors: Kispert Shannon , Kuenzel Hannah , Marentette John , McHowat Jane
Published: June 2021

Most cancer deaths are a result of metastasis rather than the primary tumor. Although cigarette smoking has been determined as a risk factor for several cancers, its role in metastasis has not been studied in great detail. We propose that cigarette smoking plays a role in increased metastasis via inhibition of endothelial cell platelet‐activating factor acetylhydrolase (PAF‐AH) inhibition, resulting in PAF accumulation and recruitment of circulating tumor cells to secondary sites. We exposed mammary epithelial cells (MCF‐10A) and breast cancer cell lines (MCF‐7, MDA‐MB‐231, and MDA‐MB‐468) to CSE for up to 48 hours. CSE inhibited PAF‐AH activity, increased PAF accumulation, and increased cell motility in the metastatic triple negative breast cancer cell line MDA‐MB‐231. Metastatic triple negative breast cancer cells exposed to CSE showed an increase in epithelial‐mesenchymal transition (EMT) as measured by the disappearance of the epithelial marker E‐cadherin and increased expression of the mesenchymal markers Snail and Slug. Thus, PAF may be a therapeutic target to manage metastatic disease, particularly in triple negative breast cancer patients who smoke.
Design and synthesis of albuterol‐derivatives as selective β2‐adrenoceptor agonists with potential biased signaling (588.2)
Authors: Lopez‐Cabrera Yessica , Trujillo‐Ferrara Jose , Cuevas‐Hernandez Roberto , Correa‐Basurto Jose , Soriano‐Ursua Marvin
Published: June 2021

The development of new drugs based on the selectivity for recognition and coupling on receptors is increasing. Recent studies of β‐adrenoceptors and their associated ligands allow us to explore properties about interactions and receptor activation, which modulated the response produced in a organism. Those responses are related with the preference of the G‐protein‐dependent pathway or the β‐arrestin pathway.

In present work, we designed albuterol derivatives and we studied them through a computational study analyzing interactions on β2 adrenoceptor using in silico tools. Furthermore, we carried out the synthesis of some of these compounds. From our in silico results, we suggest that chemical structure of albuterol derivatives influence in both orthosteric and allosteric binding sites on the receptor, in such manner which could be involved in their potencial biased signaling. Also, we suggest the potential of in silico details for suggesting biased signaling on β2 adrenoceptor. Finally, regarding the synthesis of these compounds, we identified the specific values for temperature and pH variables favoring yield and purity.

Grant Funding Source: Supported by CONACyT (CB168116), COFAA, and SIP‐IPN, México.
A small‐world network model of the suprachiasmatic nucleus showing day and night firing rates (588.3)
Authors: Elorette Catherine , Watrous James
Published: June 2021

In nature, the suprachiasmatic nucleus (SCN) of the brain controls circadian rhythms of sleep and wakefulness in response to the presence or absence of light. This study sought to create a computer model of the SCN using SNNAP (Simulator for Neural Networks and Action Potentials) (Ziv et al., 1994). Fifty seven model neurons were arranged in a small world network configuration with each neuron connected to its four nearest neighbors via excitatory connections. In vivo results were used to build the network in a way that would reflect real world results. It has been shown that the SCN consists of two sections, a core and a shell. The model core that was built consisted of 40% of the network’s neurons, including five pacemaker and five vasopressin intestinal peptide activated neurons. Model photoreceptor cells were connected to the core neurons with electrical synapses to simulate light activation. The shell comprised 60% of the network and contained most of the long distance connections. Ultimately the model produced a daytime firing rate of 8 Hz and a nighttime firing rate of 3 Hz. The model is being used to further test the effect of sudden light activation on the night firing rate.
The effect of pacemaker neurons on epileptiform activity within the CA3 and CA1 regions of the hippocampus (588.4)
Authors: Kozlowski Lauren , Watrous James
Published: June 2021

This study simulates pacemaker neurons acting on the CA3 and CA1 regions of the hippocampus and their effect on epileptiform activity. Epileptic seizures are produced from an excess of synchronous positive feedback in neural networks. Research by Netoff et al. (2004) showed that ictal bursting is observed in the CA3 region and prolonged seizures are observed in the CA1 region. Models of these regions were created with the software Simulator for Neural Network and Action Potentials (Ziv et al. 1994). Small world networks of 64 neurons were constructed with the appropriate synaptic connections and strengths, simulating the predicted epileptiform activities in voltage vs. time outputs. A network of 32 electrically connected Morris‐Lecar neurons, pacemaker neurons, were connected to randomly selected neurons in each model. Based on differences in action potential profiles produced, the CA3 region modeled prolonged seizing after the addition of the Morris‐Lecar Network causing an excess of synchronous positive feedback, rather than the expected ictal bursting; however, the prolonged seizing of the CA1 region did not change after adding the Morris‐Lecar Network.
The effect of prolonged minimal exposure of antibiotics to E. coli (598.6)
Authors: Lampley Rebecca , Boles Jeffrey
Published: June 2021

Escherichia coli (E. coli) is a normal flora bacterial species found in the lower intestines, which acts as an opportunistic pathogen, especially in hospitals and medical care facilities. The medical industry also battles drug‐resistance in such pathogenic bacteria, which usually occurs with improper use of antibiotic treatment on infections. To evaluate bacterial tolerance to antibiotics over time, this study used E. coli (Strain ATCC 23848) in the presence of Ampicillin, Tetracycline, and Kanamycin Sulfate each of which function by inhibiting cell wall synthesis. Tube dilutions tests were conducted to determine the initial minimum inhibitory concentration (MIC) of each antibiotic required to prevent E. coli cell growth. E. coli present in tubes with antibiotic concentrations less than the MIC were then cultured in non‐lethal doses. Every two weeks an MIC was performed to determine if a change in the MIC had occurred.
The effect of hypoxia on lipid raft organization and host‐pathogen interactions of intestinal epithelial cells (599.2)
Authors: Zeitouni Nathalie , Branitzki‐Heinemann Katja , von Koeckritz‐Blickwede Maren , Naim Hassan
Published: June 2021

Oxygen stress, or hypoxia, occurs in tissues during an infection, mostly due to overconsumption of oxygen by pathogens and recruited immune cells. The aim of this study is to analyze the effect of hypoxia on host‐pathogen interactions and cellular responses of the intestinal epithelium upon infection. Therefore, Caco‐2 cells were grown under normoxia or hypoxia and were infected with Yersinia enterocolitica, a Gram‐negative bacterium that can cause severe gastrointestinal infections. Results show that invasion of Caco‐2 by Y. enterocolitica was significantly reduced in hypoxia‐treated cells while adherence remained unchanged. Since intestinal epithelial cells have been shown to regulate host‐pathogen interactions by means of detergent‐resistant membrane domains called lipid rafts, we further investigated the effect of hypoxia on lipid rafts. Interestingly, separation of lipid rafts isolated from Caco‐2 cells grown under hypoxia demonstrated that flotillin, a lipid rafts protein marker, exhibits a diffuse pattern in the rafts as well as non‐rafts fractions. By contrast, cells grown under normoxia revealed a clear flotillin distribution in the floating lipid rafts fractions. These results indicate that hypoxia leads to alterations of the intestinal epithelial cell membrane and suggests a protective effect of these membrane changes on host cells by hindering invasion of Y. enterocolitica.

Grant Funding Source: Supported by DAAD and the German Research Council (DFG, grant number KO355214).
Functional motif analysis for glycosyltransferases in apicomplexan genomes (608.5)
Authors: Datta Arun , Sinai Anthony , Kissinger Jessica
Published: June 2021

Parasitic protozoa of the Phylum Apicomplexa include the genus Plasmodium (causative agents of malaria) and Toxoplasma gondii which causes toxoplasmosis. Little is known about glycosylation pathways and their contributions to pathogenesis. Increased glycosylation is known to be a feature of the chronic infection with Toxoplasma defined by the formation of the tissue cyst. Lectin reactivity and biochemical identification indicate that Toxoplasma tissue cysts contain diverse glycan modifications that are hypothesized to originate from both the parasite and the host. In order to establish the potential extent of host derived glycan modifications we have undertaken a comprehensive survey of the encoded potential in the toxoplasma genome (www.toxodb.org) by conducting a rigorous bioinformatics survey for predicted glycosyltransferases (GT). In addition to the identification of a truncated pathway for the synthesis of N‐linked glycans predicting simple (ConA positive) but not complex (LCA positive) labeling we find a complete absence of any of the machinery to permit modification with sialic acid. The presence in tissue cysts of both complex N‐linked glycans and sialic acid (SNA, MALII, Limax agglutinin and anti Sia‐Tn antigen) implicates host cell involvement. In order to understand the full extent of the novel form of parasitism, the hijacking of host glycan modifying enzymes, we are now investigating whether the Toxoplasma genome encodes other classes of glycosyltransferases. We hypothesize that the absence of a specific GT encoded in the parasite genome coupled with its phenotypic detection implicates thievery from the host cell. The current interrogation is being extended to other parasitic protozoa for which the genomes are now available (www.eupathdb.org). Such a broad survey across Apicomplexa and other parasitic Phyla may reveal insights into the evolution of the glycosylation machinery in these early branching eukaryotes and provide insights into infection and immunity.

Grant Funding Source: NIHR21 AI099509 (to APS)
HGF‐independent regulation of MET and Gab1 through non‐receptor tyrosine kinase FER (609.4)
Authors: Fan Gaofeng , Gao Yan , Greer Peter , Tonks Nicholas
Published: June 2021

HGF‐MET signaling has versatile functions in tissue remodeling, wound repair, organ homeostasis and cancer metastasis. Activation of MET involves HGF ligand association and relayed receptor autophosphorylation on tyrosine residues within its kinase domain, followed by tyrosine residues within its C‐terminal docking domain. Here, we reported an alternative, HGF‐independent activation of MET through a non‐receptor tyrosine kinase FER. By using ovarian cancer as model, we observed up‐regulation of FER in a panel of the ovarian cancer cell lines. RNAi‐mediated inactivation of FER robustly decreased the cancer cell motility in vitro, and the ability to metastasize to liver and lung in vivo, and rescue experiments indicated that tyrosine kinase activity of FER was essential. Of great interest, we demonstrated that FER modulated activities of MET and Gab1 in an HGF‐independent manner, with both being substrates of the kinase. Consistently, loss of FER sensitized ovarian cancer cells to MET inhibitor PHA‐665752. Meanwhile, we also observed the significant loss of membrane distribution of MET in the absence of FER, as well as of its tyrosine kinase activity. Further analysis suggested FER sustained MET on the membrane to delay both inactivation by protein‐tyrosine phosphatase 1B. In conclusion, our study, for the first time, illustrated multiple functions of FER in regulation of MET‐mediated signaling pathway.
Decision making in C. elegans chemotaxis to alkaline pH (612.1)
Authors: Sassa Toshihiro , Murayama Takashi , Maruyama Ichiro
Published: June 2021

Monitoring of environmental and tissue pH is crucial for animal’s survival behavior. The nematode C. elegans is an excellent model organism for analysis of neural circuits that regulate animal behavior. The animal is attracted to mildly alkaline pH, but avoids strongly alkaline pH. Here we analyzed the chemotactic behavior at molecular and cellular levels. Genetic dissection and Ca2+ imaging demonstrated that ASEL and ASH are the major sensory neurons responsible for attraction to mildly alkaline pH and repulsion from strongly alkaline pH, respectively. In ASEL, A transmembrane guanylyl cyclase, GCY‐14, is activated by mildly alkaline pH, and in turn opens a cGMP‐gated cation channels consisting of TAX‐2 and TAX‐4. It has also been shown that a specific histidine residue plays an essential role in the extracellular alkaline pH. In ASH, TRPV channels consisting of OSM‐9 and OCR‐2 are activated by strongly alkaline pH for Ca2+ influx into the neuron. A G‐protein α subunit, GOA‐1, is also required for its avoidance behavior perhaps through regulating synaptic vesicle exocytosis in ASH. By analyzing chemotactic behavior of various mutants, we also found that activities of ASEL and ASH compete each other for decision making or behavior switching in C. elegans chemotaxis to alkaline pH. While mildly alkaline pH preferentially activates ASEL, strongly alkaline pH activates both ASEL and ASH, and ASH activity overrides the activity of ASEL. Neural circuits responsible for this decision making will be discussed.
Microarray analysis for the influence of CMV infection on tomato genomes (617.1)
Authors: Montasser Magdy , Ai‐Ajmy Afrah , Al‐Mulla Fahd
Published: June 2021

Functional genomics is the study of gene function through parallel expression measurements of a genome. The most common tools used to carry out these measurements include complementary DNA microarrays, oligonucleotide microarrays or serial analysis of gene expression (SAGE)3. A custom‐designed Affymetrix tomato GeneChip array was used to study the gene expression changes in response to viral inoculation with a mild and severe CMV strains. The basic technique involves extraction of RNA from tomato leaf samples and then copied, while incorporating either fluorescent nucleotides or a tag that is later stained with fluorescence. Labeled RNA is then hybridized to a microarray for a period of time, then excess is washed off and the microarray is scanned under laser light. Different expression responses were resulted due to the type of viral infection.Total number of expressed genes were 3213, Out of this 1660 genes were down‐regulated and 1553 were up‐regulated. The response to CMV‐16 infection led to 1365 gene expression, 642 were down‐regulated and 723 genes were up‐regulated Specific seven different genes in tomato genome (Hsp70,ChMDH, Wif1, rccr, AAP2, PIIF & GAPDH endogenous gene used as a control) were analyzed and resulted in down regulation of Hsp70 and upper regulation of both ChMDH and PIIF. Gene expression results were confirmed with relative quantitative RT‐PCR technology.
Increased retention from a summer‐bridge program focused on academics, community, and leadership (618.34)
Authors: Lo Stanley , Flores Luke , Drane Denise , Swarat Su , Beitel Greg , Light Gregory
Published: June 2021

Under‐represented minority students leave science, technology, engineering, and mathematics (STEM) majors at high rates. As an intervention, pre‐college summer‐bridge programs have been successful. However, evaluations of existing programs focus on degree attainment and lack information on student experience while in college. Traditional summer‐bridge programs also emphasize ethnic backgrounds and academic under‐preparedness. We report a new summer‐bridge program that aims to address gaps in the literature described above.

The new summer‐bridge program is different from traditional programs in significant ways. First, the definition of under‐representation is expanded to include socioeconomic need, first‐generation college student, and multilingualism. Second, the selection criteria focus on demonstrated commitments to promoting diversity and inclusion instead of ethnic backgrounds to avoid activation of stereotype threat. Third, courses are offered at different levels to challenge students regardless of academic preparation. Finally, the program is designed to engage participants in activities that focus on community building, leadership development, and authentic practices in biological research.

A quasi‐experimental design with a historical comparison group (n=708) is used to study the effectiveness of this program. To date, three cohorts of participants (n=58) have completed the program. Pre‐ and post‐surveys reveal significant increases in reported help‐seeking, propensity for critical thinking, and knowledge of research process. In focus groups and interviews, participants reported that the program helped them connect with faculty, establish social networks, and become part of the university community. Critically, compared to a historical cohort, participants have higher grades (2.53±0.62 vs. 1.94±0.92, p<0.01) and retention rates (73% vs. 30%, p<0.01) in General Chemistry, the gateway course to many STEM disciplines including biology.

Grant Funding Source: Howard Hughes Medical Institute
Prevalence and risk factors for malnutrition in children with congenital heart disease, Ho Chi Minh City, Viet Nam (620.12)
Authors: Tin Hoang , Nhan Le , Hoa Nguyen , Giang Do Thi , Ziegler Thomas , Lenders Carine
Published: June 2021

Objective: To determine the prevalence and risk factors for malnutrition in children with congenital heart disease (CHD) attending a cardiology clinic in Vietnam.

Methods: Cross‐sectional survey of all children with CHD aged <5 years old at Children’s Hospital #1 (March‐August 2012). Data included weight (W), height (H), age (A), gender, cardiac diagnosis, severity of CHD, corrective surgery status, birth order, preterm delivery, low‐birth‐weight (LBW), breastfeeding initiation and cessation, age at weaning, parent education and income stability. Patients with genetic syndromes, dysmorphic features, or neurologic disabilities were excluded (n=9). Nutrition status was classified using WHO standards.

Results: Participants were 410 children; 153 had previous corrective surgery. The rate of stunting (H/A 蠄‐2SD) was 153/410 (37.4%) and that of wasting (W/H 蠄‐2SD) was 136/410 (33.3%). These rates did not differ according to surgery status (P>0.05). Risk factors for stunting included preterm delivery, LBW, mother’s income stability, and father’s education, (P<0.05). Risk factors for wasting included age 6‐12 mo, LBW, breastfeeding cessation at <6 mo and weaning at <6 mo (p<0.05).

Conclusion: Malnutrition rates are high in this cohort of Vietnamese children with CHD. Modifiable factors (breastfeeding and age at weaning) play a role. Prospective studies on nutritional status in this CHD patient population are needed to inform intervention studies.

Grant Funding Source: Support from the Abbott Fund
Adjustment of RNA‐Seq data for the effect of highly abundant transcripts: a case study in milk production (622.4)
Authors: Beck Kristen , Turco Gina , Bradnam Keith , Rijnkels Monique , Nommsen‐Rivers Laurie , Korf Ian , Lemay Danielle
Published: June 2021

During lactation, profound changes occur in the mammary gland and thousands of genes undergo differential regulation. RNA‐seq data analysis reveals a tiny minority of milk genes account for the vast majority of total gene expression. This striking imbalance in transcript abundances poses a significant problem for data analysis, e.g. low abundance genes may be incorrectly identified as downregulated. To tackle this problem, we developed a ‘Dilution Adjustment Model’ which more accurately classifies changes in levels of low abundance transcripts between transcriptomes at two developmental stages (baseline and mature lactation). Applying this model to human and bovine milk data led us to reclassify 2,155 human (971 bovine) genes as ‘upregulated’ instead of ‘not differentially expressed’ and 2,524 human (1,732 bovine) as ‘unregulated’ instead of ‘downregulated’. Changes in gene classification were supported by analysis of Gene Ontology and TFBS enrichment profiles. Investigation of ChIP‐Seq data showed genes reclassified as ‘upregulated’ exhibit signs of active transcription and reclassified ‘unregulated’ genes match marks of others in this set. This work leads to a better understanding of transcription mechanisms in milk production. Application of this model to other biological systems is relevant where transcripts from a minority of genes dominate transcriptome composition.

Grant Funding Source: K.B was supported by Grant Number T32‐GM008799 from NIGMS‐NIH
Understanding the implementation, utilization, and potential impact of a social franchise model to improve infant and young child feeding practices in Vietnam: a program impact pathway analysis (624.10)
Authors: Nguyen Phuong , Menon Purnima , Keithly Sarah , Hajeebhoy Nemat , Tran Lan , Ruel Marie , Rawat Rahul
Published: June 2021

Program impact pathway (PIP) analysis helps to lay out and study the causal links between program activities, outcomes and impacts. This PIP analysis‐based study examines the pathways by which the Alive & Thrive (A&T) social franchise model is expected to improve infant and young child feeding (IYCF) practices in Vietnam. Mixed methods (surveys, observations, facility assessments) were used to assess the following elements of the PIP: 1) training and knowledge of frontline health workers (FHWs) (n =447); 2) quality of service delivery and communication with clients (n =166); 3) mothers’ service utilization (n = 2,045); and 4) the program’s role in shaping maternal behavioral determinants of IYCF practices. A&T training was associated with improved FHWs’ IYCF knowledge and counseling skills, resulting in higher quality IYCF counseling. Franchise utilization increased from 10% in 2012 to 45% in 2013, but utilization fell far below the expected 9‐15 contacts specified in A&T guidelines. Improvements in breastfeeding knowledge, intentions, and beliefs were greater among mothers in intervention areas with social franchise and mass media, compared to media alone. In conclusion, many aspects of the franchise services are encouraging, but challenges in service delivery and utilization along the PIP should be addressed to achieve the full intended impact.

Grant Funding Source: Funded by Bill & Melinda Gates Foundation, through Alive & Thrive, managed by FHI360
Prebiotic intervention improves dyslipidemia and body composition (624.29)
Authors: Dey Moul , Specker Bonny , Wey Howard , Weidauer Lee , Nichenametla Sailendra
Published: June 2021

A metabolic health crisis is well recognized as cardiovascular diseases remain the leading cause of mortality. Effects of RS4, a prebiotic fiber, in comprehensive management of metabolic syndrome (MetS) remain unknown. This study examined the effects of a blinded exchange of resistant starch type‐4 (RS4)‐enriched flour (30% v/v) with regular/control flour (CF) diet on multiple MetS comorbidities. In a double‐blind, placebo‐controlled, cluster crossover intervention (n=86, age蠅18, 2 12‐week interventions), individuals were classified as having MetS (With‐MetS) or not having MetS (No‐MetS) following IDF criteria. RS4 consumption compared with CF resulted in 7.2% (p=0.002) lower mean total cholesterol (TC), 5.5% (p=0.04) lower non‐HDL, and a 12.8% (p<0.001) lower HDL cholesterol in the With‐MetS group. Individuals in the No‐MetS group had a 2.6% (p=0.02) smaller waist circumference and 1.5% (p=0.03) lower percent body fat following RS4 intervention compared to CF. A small but significant 1% increase in fat‐free mass also was observed in all participants combined (p=0.02). No significant effect of RS4 was observed for glycemic variables and blood pressure. RS4 consumption improved dyslipidemia and body composition. Functional and adaptable prebiotic food ingredients such as RS4 could be an effective strategy for public metabolic and cardiovascular health promotion. NCT01887964 at clinicaltrials.gov.

Grant Funding Source: Funding from MGP Ingredients, Atchison KS (# 3P2662), SDAES (#AH360) to MD , EAM to BS
Education and work incentives for frontline workers and household socioeconomic status influence delivery of health and nutrition interventions in Bihar, India (624.5)
Authors: Avula Rasmi , Kosec Katrina , Holtemeyer Brian , Tyagi Parul , Hausladen Stephanie , Menon Purnima
Published: June 2021

In Bihar, India, coverage of essential nutrition interventions is low, but little is known about the factors associated with service delivery by FLW and utilization of services by HH. Data: A cross‐sectional survey of 790 FLWs and 6002 HH from 400 villages in 1 district in Bihar. Analysis: Multivariate regression analysis to examine supply‐ and demand‐side determinants of whether HH receive immunization, food supplements (FS), pregnancy care information (PCI) or nutrition information (NI). Supply side determinants varied by outcome: incentives for FLW were marginally positively associated (p<0.1) with immunization; FLW living outside their service areas was negatively associated with FS to HH (p<0.1); FLW education (p<0.05), use of pregnancy registers (p<0.05) and incentives (p<0.05) were positively associated with PCI. Demand side determinants varied by outcome: having a more educated HH head was associated with greater immunization; lower SES HH were more likely to get FS (p<0.05), but higher SES HH (p<0.05) and HH who had visited nutrition centers (p<0.05) were more likely to get NI. Conclusion: FLW education, proximity to area of service, and incentives affect service delivery outcomes, but HH factors are also important. Recruiting more educated candidates as FLW, investing in incentives, and enhancing HH contacts with nutrition centers through demand creation could improve service delivery outcomes.

Grant Funding Source: Supported by Bill & Melinda Gates Foundation, through POSHAN led by IFPRI
Trends in trans fatty acid levels in the Canadian food supply (632.12)
Authors: Arcand JoAnne , Scourboutakos Mary , Au Jennifer , L'Abbe Mary
Published: June 2021

Dietary trans fatty acids (TFA) increase risk for heart disease. In 2007, Canada adopted voluntary TFA limits for food (<5% total fat, <2% total fat for fats) and recommended that unsaturated fat replace TFA, over saturated fat. Mandatory TFA labeling was implemented and a government‐led Trans Fat Monitoring Program (TFMP) measured and publicly reported TFA levels by company/brand. This study assessed changes in TFA levels in the food supply and if saturated fats are higher in foods with lower TFA. Data from Health Canada’s TFMP (n=921, 2006‐2009) and the University of Toronto food (n=5544, 2010‐2011) and restaurant (n=4272, 2010) databases were used. The proportion of foods meeting TFA limits improved from 75.4% in 2006‐2009 to 96.1% in 2010‐2011, particularly in packaged foods: croissants (25 to 100%), pies (36 to 98%), cakes (43 to 90%), and garlic spread (33 to 100%). Most TFMP restaurant categories, except for muffins (95%) had 100% of foods meeting TFA limits in 2010. Some food categories had a large proportion of foods exceeding TFA limits: dairy‐free cheeses (100%), frosting (72.0%), shortening (66.7%), coffee whiteners (66.7%), and restaurant‐prepared biscuits and scones (47.4%). Coffee whiteners, donuts, popcorn and frosting that exceeded TFA limits contributed >25% TFA to total fat. Saturated fat was higher (p<0.05) in some foods with low TFA levels: chocolate chip, chocolate covered and sandwich cookies, brownies and squares, cakes with pudding/mousse, dessert topping, and among restaurant‐prepared cookies. There is an impressive improvement in TFA levels in the Canadian food supply, demonstrating that voluntary limits and monitoring are effective in reducing TFA in the food supply. Efforts should focus on reducing TFA where levels remain high and on limiting the use of saturated fat to replace TFA.
Maternal microbiota ő source of novel tools to fight non‐communicable disease risk? (637.12)
Authors: Collado Maria Carmen , Rautava Samuli , Aakko Juhani , Isolauri Erika , Salminen Seppo
Published: June 2021

Background: Pregnancy and early infancy comprise the most critical stage for programming of later health.

Objective: The evolution of microbial contact of mother and her neonate was assessed.

Methods: We recruited 43 consecutive women who were scheduled to undergo elective cesarian section at term. Amniotic fluid and placenta samples were taken during delivery in a sterile manner. Fecal and colostrum samples from to mother, meconium and 3‐4 day fecal samples from neonate were collected. Microbial diversity was analyzed by PCR‐DGGE and qPCR. Bacterial presence in placenta and amniotic liquid was further characterized by traditional culturing methods. The subjects with complete set of samples were included in the analysis.

Results: Bacterial DNA was present in all samples including placenta, amniotic liquid and colostrum, and qPCR demonstrated the presence of Lactobacillus, Bifidobacterium, Staphylococcus and Streptococcus in all samples analyzed. Specific microbes isolated from placenta and amniotic liquid identified as Propionibacterium and Staphylococcus spp. PCR‐DGGE showed diverse DNA fragments shared by the mother and her neonate, such as those belonging to Leuconostoc, Weisella, Lachnospiraceae, Bifidobacterium and Lactobacillus spp.

Interpretation: Microbial contact begins prior to birth and is shaped by the maternal microbiota. The mother and infant share similar microbes in most interfaces. Thus, maternal microbiota may prove a safe and effective target for interventions aiming to reduce the risk of non‐communicable diseases in future generations.

Grant Funding Source: Supported by the Academy of Finland
Flaxseed and buckwheat supplemented diets altered bacterial populations in the cecum and feces of mice (637.6)
Authors: Pulkrabek Margaret , Gibbs Penelope , Rhee Yeong , Hall Clifford , Blodgett‐Salafia Elizabeth
Published: June 2021

Depending on the host’s dietary intake, bacterial populations in the gastrointestinal tract can vary in abundance and diversity. The objective of this research was to determine the growth and diversity of bacteria in the cecum and feces following flaxseed and buckwheat supplemented diets. Seventy‐two C57BL/6J male mice were randomly assigned into one of the following diet groups and fed for eight weeks: Group 1 (45% Kcal fat, control); Group 2 (45% Kcal fat, 10% whole flaxseed); Group 3 (45% Kcal fat, 6% defatted flaxseed); Group 4 (45% Kcal fat, 4.5% flaxseed oil); Group 5 (45% Kcal fat, 10% buckwheat); and Group 6 (control diet, 12% Kcal fat, pair‐fed to group 2). At week nine, fecal and cecum samples were collected for bacteria isolation. Significant differences in bacterial growth in the cecum (p < 0.0348) and feces (p < 0.0033) were observed among treatment groups. Within the Family of Enterobacteriaceae, including Serratia liquefaciens, Enterobacter cloacae, and Pantoea agglomerans, whole flaxseed and buckwheat groups showed the most growth and bacterial diversity. The flaxseed oil and high fat diets had the least. In conclusion, whole flaxseed and buckwheat supplementation altered bacterial growth and diversity in the cecum and feces of mice.
Effect of caloric and non‐caloric sweeteners on liver lipid metabolism in rats (642.5)
Authors: Janssens Sharon , van Riel Natal , Nicolay Klaas , Prompers Jeanine
Published: June 2021

Objective: Examine lipid metabolism in liver of rats receiving different caloric and non‐caloric sweeteners using magnetic resonance spectroscopy (MRS). Methods: 24 male Wistar rats (343 ± 2 g) were divided into 4 diet groups receiving water (CON), 13% glucose solution (GLU), 13% fructose solution (FRUC), or 0.4% aspartame solution (ASP). After 7 weeks of diet, 1H‐[13C] experiments were performed at baseline and after oral administration of 1.5 g [U‐13C] Algal lipid mixture per kg body weight. Results: After 7 weeks, body weight of GLU animals was higher compared with ASP animals. Although animals in the GLU and FRUC groups consumed less food compared to CON and ASP animals, their total energy consumption was higher due to the excess intake of calories from sugar in their drinking water. Total liver lipid content was higher in GLU and FRUC animals compared with ASP animals. Four hours after the administration of 13C‐labeled lipids, 13C enrichment of intracellular lipids was equally increased in all 4 groups, showing that dietary lipid uptake was not different between groups. Conclusion: The non‐caloric sweetener aspartame did not have any effect on liver lipid content or metabolism. Glucose and fructose consumption resulted in increased lipid content in the liver, which was not accompanied by an increased uptake of dietary lipids and is thus likely caused by elevated lipogenesis.

Grant Funding Source: Supported by the Netherlands Consortium for Systems Biology (NCSB)
Lipid emulsion and exercise reduce the development of hepatic steatosis in mice fed high‐dextrose parenteral nutrition formula (642.9)
Authors: Huang Kuan‐Hsun , Hao Lei , Ross A.
Published: June 2021

Lipid emulsions (LE) are used to prevent essential fatty acid (EFA) deficiency in patients receiving parenteral nutrition (PN), which contains a high percentage of dextrose related to the occurrence of hepatic steatosis. We have previously shown, in 4‐5‐week studies, that LE given either orally or i.v. ameliorates triacylglycerol (TG) accumulation in the liver of nonobese mice fed PN formula orally. Currently, we have conducted a short‐term study (8‐d) to determine whether administration of LE and exercise (Ex, voluntary running), modulates the expected increased expression level of genes associated with fatty liver disease. 5‐wk‐old male C57BL/6 mice were randomized into 5 groups: normal reference group (NC, fed rodent chow); PN only (with 0.5% EFA to assure adequacy); PN+Ex; PN+ 13.5 (en‐%) LE; or PN+LE+Ex. Oil Red O staining and TG analysis showed that hepatic TG contents were increased after 8 d in the PN and PN+Ex groups (P<0.05), compared to NC. The addition of LE suppressed the TG increase caused by PN. Quantitative PCR analysis showed that LE significantly decreased expression of the hepatic patatin‐like phospholipase domain‐containing protein‐3 (PNPLA3) gene (P<0.01), and addition of exercise reduced fibroblast growth factor‐21 levels in liver and plasma. Our results suggest that LE and exercise play protective roles in the development of hepatic steatosis induced by high carbohydrate diet.
Global metabolite analyses of serum, muscle and liver reveals a shift in metabolism to favor fatty acid oxidation and energy expenditure (643.10)
Authors: Kim Jeffrey , Newman John , Pappan Kirk , Fiehn Oliver , Carlson Morgan , Kuchel George , Watkins Bruce
Published: June 2021

Global metabolite analysis grouping various pathways represents a powerful and practical means of establishing links to health and disease status. Lipid‐based metabolites, such as the arachidonate (AA)‐derived ligands of the endocannabinoid system (ECS), appear to regulate whole body energy balance and shift anabolic pathways, with overactivation of the ECS associated with obesity and type 2 diabetes. Since ECS activation relies on lipid‐derived ligands, namely AA, we conducted an investigation to determine how dietary PUFA influence the ECS to affect glucose clearance. C57BL/6 mice were fed a control or DHA containing semi‐purified diet for 118 d. Serum, gastrocnemius, and liver were collected after 62 d and 118 d for metabolomics analyses. Epididymal fat mass was lower in mice given DHA but no difference in body weights or food intakes were observed compared to controls. Metabolite profiles portrayed a shift from glucose use to favoring fatty acid oxidation with DHA. Higher levels of DHA‐containing glycerol lipids were found in mice fed the DHA diet, as well as a decrease of AA‐derived ECS ligands, suggesting diminished ECS activation. Analysis of serum oxylipins showed higher levels of LOX and CYP pathway products in mice fed the control diet. These findings demonstrate that mice given DHA suppress the ECS by dampening activation potential resulting in meaningful changes in macronutrient metabolism and physiology.
Brain biomarkers derived by proton magnetic resonance spectroscopy may indicate brain energetic changes in Alzheimer’s disease (643.12)
Authors: Taylor Matthew , Swerdlow Russell , Vidoni Eric , Morris Jill , Sullivan Debra , Burns Jeffrey
Published: June 2021

BACKGROUND: Metabolic changes in the brain have been proposed to lend to Alzheimer’s disease (AD) etiology. Proton Magnetic resonance spectroscopy (MRS) allows in‐vivo measurement of brain metabolites that have been implicated in brain energy metabolism.

METHODS: 120 subjects 蠅65 years old (58 non‐demented, CDR 0; 50 very mild AD, CDR 0.5; and 12 mild AD, CDR 1.0) were included in this cross‐sectional study. Brain concentrations of n‐acetyl aspartate (NAA), myoinositol (MI), glutamate+glutamine (Glu+Gln) and creatine (Cr) were measured in 6 different brain regions via MRS. ANOVA was performed using CDR 0 as the control.

RESULTS: MI was elevated in posterior gray matter in both AD groups (p=.01, p=.05) and elevated exclusively in CDR 0.5 in left frontal white matter (p=.04) and right frontal white matter (p=.04). NAA was reduced in CDR 0.5 left frontal white matter (p=.05) and left temporal white matter (p=.04) and reduced in CDR 1.0 expressed as NAA/Cr in posterior gray matter (p=.01). Glu+Gln/Cr was reduced in in both AD groups in posterior gray matter (p=.04, p=.01) and right temporal white matter (p=.04, p=.02) and in left frontal white matter (p=.02) in CDR 0.5.

DISCUSSION: Biomarkers measured by MRS suggest differences in brain metabolism in AD compared to non‐demented aging. Causality of these changes and their consequence in AD is unknown. It is desirable to know whether diet or therapy could play a role in normalizing biomarker concentrations and offer benefit in AD.
Synergistic anti‐cancer effects of capsaicin and 3,3’‐diindolylmethane in human colorectal cancer, involvement of NF‐κB and p53 (644.11)
Authors: Clark Ruth , Lee Seong Ho
Published: June 2021

Cancer is the second leading cause of death in the United States and a leading cause of morbidity and mortality worldwide. A promising area of cancer research is focused on chemoprevention by nutritional compounds. Epidemiological studies have shown a strong negative correlation between fruit, vegetable and spice intake and rates of cancer. Although individual active compounds have demonstrated significant anti‐cancer activity, an emerging area of research is focusing on the combination of multiple dietary compounds on cancer that act synergistically to exert greater effects. In the current study, we evaluated potential synergistic effects of capsaicin, an active compound from red chili peppers, in combination with 3,3'‐Diindolylmethane (DIM), from cruciferous vegetables. A synergistic induction of apoptosis and inhibition of cell proliferation was observed in the human colorectal cancer cells treated with combination of capsaicin and DIM. We also observed that these two compounds activated transcriptional activity of NF‐kB and p53 synergistically. Combination treatment stabilized nuclear p53 and up‐ or down‐regulated expression of several target genes that are downstream of NF‐kB and p53. The present study suggests capsaicin and DIM work synergistically to inhibit cell proliferation and induce apoptosis in colorectal cancer through modulating transcriptional activity of NF‐κB, p53 and target genes associated with apoptosis.

Grant Funding Source: American Cancer Society, University of Maryland
Fermentation characteristic and increased health functionality of kimchi by kimchi lactic acid bacteria starters (644.14)
Authors: Park Kun‐Young , Bong Yeon‐Ju , Kim Hee‐Young
Published: June 2021

Fermentation characteristics and health functionalities of kimchi by inoculating kimchi lactic acid bacteria (LAB) starters were studied. We isolated two kinds of LAB (Lab. plantarum pnu and Leu. mesenteroides pnu), and manufactured single LAB starter kimchis (Lab. plantarum pnuK, Lab. plantarum 3099K, Leu. mesenteroides pnuK), mixed LAB starter kimchis (Lab. plantarum pnu/Leu. mesenteroides pnuK, Lab. plantarum 3099/Leu. mesenteroides pnuK) with inoculum size of 106 CFU/g and naturally fermented kimchi (NK) as a control. These kimchis were fermented for 6 days at 15℃. Kimchi with the starters rapidly decreased in pH and increased in acidity. During fermentation, kimchis with or without Lab. plantarum (LP) showed similar levels of total aerobic bacteria and Lactobacillus sp., but kimchis with the Leuconostoc sp. showed higher levels of Leuconostoc sp. than the kimchis without the inoculation. LAB inoculated kimchis showed higher antioxidative effects than NK. In the MTT assay of HCT‐116 and HT‐29 human colon cancer cells, LPpnuK exhibited the highest inhibition rates (77.1 and 68.8%). In mRNA expressions of the LAB inoculated kimchis, Bax, p53 and p21 were increased, and Bcl‐2, iNOS and COX‐2 were decreased. Therefore, inoculating of LAB starters can promote health beneficial effects of kimchi.
Justicidin A‐induced autophagy inhibits apoptosis of human hepatocellular carcinoma Hep 3B cells (644.7)
Authors: Su Chun‐Li , Wu Hsing‐Chih
Published: June 2021

Justicidin A (JA) is a new and pure arylnaphthalide lignan isolated from Justicia procumbens, which has been used as an herbal remedy in Taiwan and China for fever, cancer, and pain. Our previous report shows that JA induced apoptosis of human hepatocellular carcinoma (HCC) Hep 3B cells, leading to the suppression of tumor cell growth in NOD‐SCID mice. Here we reveal that treatment of JA not only increased the expression of autophagic marker microtubule‐associated protein 1 light chain‐II (LC3‐II) by immunoblotting, but also augmented the formation of acidic vesicular organelles by flow cytometry. Administration of autophagy inhibitor bafilomycin A1 (BAF) increased protein expression of LC3‐II and lysosomal marker LAMP2a and decreased colocalization of LC3 and LAMP2a puncta by confocal microscopy, confirming that JA not only induced autophagy but also completed the autophagic flux. JA‐induced autophagy was observed via activation of Raf/MEK/ERK pathway, and was not associated with inhibition of class I PI3K/Akt/mTOR or induction of class III PI3K/Beclin 1 pathway. The novelty of JA is that pre‐treatment of cells with BAF elevated the percentages of cells at sub‐G1 phase and raised the expression of cleaved caspase 3. All together, our data suggest the use of autophagy inhibitor should be taken into consideration to enhance the chemotherapeutic potential of JA for treatment of human HCC.

Grant Funding Source: Supported in part by the National Science Council, Taiwan, No. NSC 98‐2313‐B‐003‐002‐MY3
Variants in the β,β‐carotene monooxygenase‐1 gene are associated with elevated plasma high density lipoprotein cholesterol levels in young Mexican adults (645.19)
Authors: Marques Courtney , Andrade Flavia , Aradillas‐Garcia Celia , Erdman John , Teran‐Garcia Margarita
Published: June 2021

Retinoic acid and retinol are important mediators of a multitude of metabolic processes in the human body, including lipid metabolism. Major dietary precursors of retinoids include the pro‐vitamin A carotenoids. Beta‐carotene, which is cleaved by the enzyme BCMO1, can be a principle source of retinoic acid in the diet. Within the BCMO1 gene, single nucleotide polymorphisms (SNPs) (rs6564851 and rs10048138) have been found to affect activity of this enzyme. Previously, associations between these SNPs and plasma lipid levels have been observed in U.S. cohorts but have not been replicated in the Mexican population. Our objective was to examine the association between differences in genotype of BCMO1‐rs6564851 and rs10048138 and plasma lipid levels in a cohort of young Mexican adults (n=374). DNA was obtained from whole blood and was genotyped using the Taqman system. General linear models were used to systematically analyze associations. Both SNPs were in Hardy‐Weinberg Equilibrium with minor allele frequencies of 0.53 and 0.29, respectively. We found a genetic association between a haplotype constructed with these two SNPs and plasma HDL‐C levels. Regardless of BMI category and smoking status, minor allele carriers were associated with elevated plasma HDL‐C (p<0.02). These results suggest that the SNPs in the BCMO1 gene could confer changes in enzyme activity that could affect risk for dyslipidemia.

Grant Funding Source: University of Illinois at Urbana‐Champaign Research Board grant 09070 (to F. Andrade)
Astaxanthin ameliorates UVB‐induced inflammation in keratinocytes and keratinocyte‐dependent MMP‐1 production in fibroblasts in vitro (645.2)
Authors: Yamashita Eiji , Hongo Nobuko , Tominaga Kumi
Published: June 2021

Recently, astaxanthin has been reported to have the cosmeceutical benefits for human skin. To investigate the mechanism of action we examined the effects of astaxanthin on the UVB‐induced production of inflammatory cytokines and mediators in human epidermal keratinocytes and on the keratinocyte‐dependent induction of matrix‐metalloproteinase (MMP)‐1 in human dermal fibroblasts in vitro. As the results, astaxanthin treatment significantly inhibited the production of IL‐1α, IL‐6, IL‐8, TNF‐α, PGE2 and POMC induced by UVB irradiation in the keratinocytes. The conditioned media from UVB irradiated keratinocyte culture significantly increased the production compared to the media from non‐UVB culture. The increased production of MMP‐1 treated by the conditioned media from UVB irradiated keratinocyte culture was significantly inhibited by the supplementation of conditioned media from UVB irradiated keratinocyte culture with astaxanthnin treatment. The inhibition was in a dose dependent manner. It suggests that astaxanthin ameliorates UVB‐induced inflammation in keratinocytes resulting in the inhibition of UVB‐induced damage such as melanin production and wrinkle formation in not only epidermal keratinocytes but dermal fibroblasts of the skin.