bluuebunny/crossref_metadata_2025 huggingface dataset:
High throughput mutation profiling of lung adenocarcinoma
Authors: Sholl Lynette Marie , Garcia Elizabeth , Jia Yonghui , MacConaill Laura , Lindeman Neal
Published: June 2021

Mutation profiling of lung adenocarcinoma (ACA) identifies patients for targeted therapies and clinical trials. We utilize a high throughput genotyping platform to examine mutations in common oncogenes and tumor suppressor genes (TSG) in lung ACA. Fresh frozen or formalin‐fixed paraffin‐embedded tumors were collected following written informed consent. DNA was extracted from specimens containing >;50% tumor cells using standard methods. Mutation profiling for 471 mutations in 41 genes was performed using single base extension chemistry followed by MALDI‐TOF mass spectrophotometry (Sequenom). Variant alleles were confirmed with homogenous MassEXTEND chemistry. 173 lung ACA were tested. 96 (55%) tumors contained ≥1 mutation. KRAS was most commonly mutated (57 tumors; 33%), followed by EGFR (17 tumors; 10%), BRAF (10 tumors; 6%) and CTNNB1 (7 tumors; 4%). Five cases had concurrent CTNNB1 and EGFR or KRAS mutations. PIK3CA, PTEN, STK11, TP53, CDKN2A, VHL, ERBB2, GNAS, MAP2K1 and IDH1 mutations were detected in <2% of tumors. Over half of unselected lung ACA samples had at least one mutation in this panel. This genotyping strategy underestimates the frequency of TSG mutations, where alterations are dispersed throughout the coding sequence, and has low sensitivity for variable insertion/deletion mutations, limitations that can be addressed by adoption of next generation sequencing.
NDUFS1 as a prognostic marker in lung cancer: a clinicopathological analysis of 106 cases of non‐small cell lung cancer
Authors: Su Chia Yi , Hsiao Michael
Published: June 2021

In spite of therapy available nowadays, some lung cancer patients diagnosed with early stage tend to have more aggressive prognosis. In recent years considerable concern has arisen over identifying prognostic markers. Little has been known about the relation between NADH dehydrogenase (ubiquinone) Fe‐S protein 1 (NDUFS1), a marker involved in catalysis and cell metabolism, and lung cancer. To investigate the clinicopathological characters, immunohistochemical staining for NDUFS1 was performed on 106 non‐small cell lung cancer (NSCLC) patients. Immunoreactivity was seen positive in 80 tumors and higher than corresponding non‐tumor tissues (p<0.001). In NSCLC and adenocarcinoma, positive NDUFS1 immunoreactivity was associated with lower T stage (p=0.007 and p=0.008, respectively) and longer overall survival (p=0.028 and p=0.05, respectively). It is worth pointing out that in early stage adenocarcinoma, positive NDUFS1 immunostaining had a trend toward being correlated with longer overall survival (p=0.091). NDUFS1 was further identified to interact with c‐MYC through bioinformatics database analysis. Further experimental results showed that NDUFS1 regulated c‐MYC‐associated pathway to involve tumorigenicity in vitro and in vivo. In summary, we identified a novel marker NDUFS1 which plays an important role in tumor metabolism and correlates with favorable prognosis of NSCLC.
Application of Choline and Glycine Betaine Alters Levels of Total Phosholipids in Olea europaea L. Related to Cold Hardiness
Authors: Cansev Asuman , Gulen Hatice , Ipek Meryem , Barut Erdogan
Published: June 2021

Many plants accumulate cryoprotectant compounds in response to low temperatures such as Glycine betaine (GB). GB is synthesized by a simple two‐step pathway from the primary metabolite choline (Cho). Exogenous applications can improve the growth and survival of numerous species under several abiotic stresses. Although GB and Cho are studied in various plants, only a small number of studies investigated their roles during abiotic stress in the Olea europaea L. In addition, no study has yet investigated effects of GB and Cho application on phospholipid levels. Hence, the aim of the present study was to elucidate whether accumulation and the alterations in the phospholipids were related to GB and Cho applications in cold‐tolerant (Domat) and cold‐sensitive (Manzanilla) cultivars in non‐acclimated stages. For this purpose, 50 mM of GB and Cho solutions were applied as a foliar spray on leaves of two year‐old olive genotypes for three weeks. Leaf samples were collected for evaluations of freezing tolerance and phospholipid analysis. Results revealed that total phospolipids were greater in cv. Domat than those in cv. Manzanilla parallelling to their cold hardiness. In addition, total phospholipid content was greater in GB‐applied samples than that in Cho‐applied samples. Consequently, Cho and GB applications may protect olive leaves by altering cellular phospholipid content.
Gene Expression Profiling of PC12 Cells Exposed to Manganese
Authors: Taka Equar , Mazzio Elizabeth , Goodman Carl , Reams Renee , Soliman Karam
Published: June 2021

Chronic exposure to Manganese (Mn) causes manganism with symptoms similar to Parkinson's disease. The objective of this study was to determine the molecular targets of Mn in PC12 cells. We applied microarray technology to identify molecular targets of Mn and RT‐PCR/Western to validate results. Our results showed that Mn altered the expression of 223 genes; 146 were up regulated and 77 were down regulated. The sub‐lethal dose range (38–300 μM MnCl2) initiated metabolic stress, an induction of enolase/aldolase and hemeoxygenase 1 (HO‐1) (7.7 fold). Concentrations greater than 300 μM caused production of H2O2 concomitant to increase of gene expression of antioxidant enzymes; biliverdin reductase, arsenite inducible RNA associated protein, dithiolethione‐inducible gene‐1 (DIG‐1) and thioredoxin reductase 1 with reduced expression of mitochondrial glutaryl‐coenzyme A dehydrogenase (GCDH). In conclusion the results suggest that Mn toxicity is primarily associated with dose dependent induction of HO‐1 and elevated production of H2O2, along with a minor loss of mitochondrial function. (Supported by NIH grant NCRR G12 RR03020 and G12 MD007582).
Identification of a lysophospholipid acyltransferase in the pathogenic yeast Candida albicans
Authors: Ayyash Mariam , Algahmi Amal , Oelkers Peter
Published: June 2021

Candida albicans is a yeast regularly found within the mouth and gastrointestinal tract of healthy individuals. However, systemic proliferation can lead to potentially life‐threatening infections. Two classes of anti‐fungals target membrane composition and integrity, supporting that the plasma membrane is a sensitive target. Limiting phospholipid remodeling may accentuate the effects of these antifungals. To test this hypothesis, we characterized a lysophospholipid acyltransferase in C. albicans and generated a homologous deletion strain for the encoding gene, 1881. Preliminary assays have found the 1881, double deletionmutation strains to show a mild resistance to a polyene antibiotic and two azoles. C. elegans is currently being used as a host to assay the virulence of 1881 deletion strains. To understand the role of 1881p in phospholipid remodeling, we expressed it in S. cerevisiae and performed in vitro lysophospholipid acyltransferase assays to determine substrate specificity. The Vmax/Km ratio lead to the following ranking of substrate preference: linolenoyl CoA>; oleoyl CoA>; linoleoyl CoA>; stearoyl CoA. Mass spectrometry is being used to assess differences in cellular phospholipid species after stearate pulse – chase assays in normal and deletion strains. Funded by the Office of Sponsored Research, University of Michigan – Deaborn.
Transcytosis of cholera toxin across polarized epithelia bypasses the Golgi and is dependent on GM1 acyl chain structure
Authors: Saslowsky David E. , Wagner Jessica , Lencer Wayne I.
Published: June 2021

Cholera toxin (CT) is an AB5‐subunit toxin that enters host cells by binding ganglioside GM1. GM1 carries the toxin retrograde from the apical cell surface through the trans‐Golgi network (TGN) into the endoplasmic reticulum, where a portion of the A‐subunit translocates to the cytosol to induce disease. In polarized cells that line mucosal surfaces, a fraction of the toxin enters the transcytotic pathway, moving all the way from apical to basolateral membrane, thus breeching the epithelial barrier. Here, we find that sorting of CT‐GM1 complexes into the transcytotic pathway occurs prior to delivery to the TGN or ER The closely related E. coli toxin LTIIb, which binds a different ganglioside, also enters the endosomal compartment of polarized cells but is not sorted into the retrograde or transcytotic pathways, suggesting that ganglioside structure may dictate the trafficking. To test this, we used fluor‐labeled GM1 species with defined ceramide structures applied to live cells. We found that polarized epithelia preferentially sort GM1 species with unsaturated ceramide acyl chains from apical to basolateral membranes by transcytosis. These results identify the early/common endosome as the site of GM1 sorting in polarized cells and show that trafficking depends on ceramide structure.
Shed syndecan‐1 drives tumor progression by binding to the cell surface and translocating to the nucleus
Authors: Stewart Mark , Ramani Vishnu , Sanderson Ralph
Published: June 2021

Multiple myeloma is a hematological malignancy that disseminates throughout the body. The serum of some myeloma patients contains high levels of shed syndecan‐1 (sSDC1), an independent indicator of poor prognosis. Shed SDC1 drives myeloma tumor progression in vivo, but the mechanism(s) mediating this remain unknown. Based on preliminary findings, we hypothesized that sSDC1 regulates gene expression by binding to the tumor cell surface and translocating to the nucleus. We utilized ARH‐77 cells, a human lymphoblastoid cell line lacking SDC1 expression. When grown in the presence of medium containing murine or human sSDC1, sSDC1 was taken up by these cells and translocated to the nucleus. Additionally, exogenous sSDC1 added to myeloma cells also translocated to the nucleus. Tumor cells engineered to express high levels of sSDC1 exhibited a 50% reduction in histone acetyltransferase activity and increased phosphorylated extracellular signal‐regulated kinase (p‐ERK) as compared to cells not expressing sSDC1. Shed SDC1 translocation to the nucleus and increase in p‐ERK are dependent on the presence of intact heparan sulfate chains on its core protein. These data demonstrate for the first time that sSDC1 binds to the cell surface and translocates to the nucleus of cells. Therapeutic regulation of SDC1 shedding, its binding to the cell surface or translocation to the nucleus represent novel strategies to control the progression of myeloma and other cancers.

Work supported by NIH grants CA135075 and CA138340 (to R.D.S.).
Protons as second messenger regulators of cell signaling
Authors: Isom Daniel G , Sridharan Vishwajith , Smalley David M , Clement Sarah T , Dohlman Henrik G
Published: June 2021

Coordinated changes in intracellular pH accompany a number of cellular processes and stresses. However, we have limited knowledge of the specific cellular components that are regulated by intracellular pH signals. Here we introduce a bioinformatics approach for identifying a rare class of proteins that use core networks of acidic and basic sidechains to sense small changes in pH. Using this approach we have identified candidate proton sensors that participate in several signaling networks, including G protein and MAP kinase pathways. Through detailed biochemical, biophysical, and biological studies we have confirmed that these signaling proteins behave like proton sensors both in vitro and in vivo. Our experiments indicate that these sensors respond to proton binding by adopting conformations that are susceptible to phosphorylation, and thereby modulate pathway output. Based on these findings, we propose that cells use protons as second messengers to help regulate signal transduction under conditions of stress and pH‐coupled cellular processes.
Persistent EGF Signaling Serves to Promote Lactotrope Differentiation in GH4 Pituitary Somatolactotrope Tumor Cells, whereas Activation of the PI3K/mTOR/S6K Pathway Promotes Cell Proliferation and the Transformed Phenotype
Authors: Gomez Crystal Lynna , Trudeau Tammy , Gutierrez‐Hartmann Arthur
Published: June 2021

Background

Pituitary somatotropes and lactotropes, expressing GH and PRL, respectively, retain plasticity, allowing rapid cell expansions in response to increased physiological demands. Unfortunately, very little is known about the signaling events that instruct somato‐lactotrope cells to proliferate and then terminally differentiate or that contribute to the transformed phenotype. A number of in vivo transgenic mouse studies revealed that uncontrolled activation of growth factor Ras/MAPK signaling pathways in lactotropes results in lactotrope hyperplasia. Moreover, in vitro studies using GH4 rat pituitary somato‐lactotrope tumor cell lines have shown that activated pMAPK is necessary for both short‐term proliferation and differentiation, with possibly the duration of pMAPK activation dictating differential responses. However, these proliferation studies all relied on short‐term (6–24 hrs) assays. Thus, the specific role of MAPK in durable lactotrope proliferation and differentiation responses remain unknown.

Methods

In order to directly interrogate the role of EGF and mTOR in lactotrope differentiation, proliferation and transformation, we used persistent EGF addition or pharmacological inhibitors of mTOR, to investigate the role of these pathways in GH4 cell proliferation, clonogenicity, and soft agar growth.

Results

Using long‐term proliferation, clonogenicity and soft agar growth assays, we find that treating cycling GH4 cells with 5nM EGF and mTOR inhibitors, rapamycin and Torin 1, reduced cell proliferation, clonogenicity, and soft agar growth.

Conclusion

Collectively, these data reveal that the EGF signaling pathway Ras/Raf/MAPK, promotes lactotrope differentiation, whereas activation of the PI3K/mTOR/S6K pathway regulates lactotrope proliferation and transformed phenotype.
Parallel quantitative proteomics reveals a multi‐feedback system design for terminal differentiation
Authors: Teruel Mary N. , Park Byung Ouk , Ahrends Robert , Kovary Kyle
Published: June 2021

Cell differentiation is often described as a sequence of regulatory steps that end with a terminally differentiated state. However, control theory argues that interconnected multi‐feedback systems are potentially better suited to create a robust bistable differentiation switch. Here we show that chemical and siRNA perturbations ‐ combined with selective reaction monitoring (SRM) mass spectrometry ‐ enables a systematic identification of the molecular players and relevant feedback loops of nuclear regulators that drive differentiation. Markedly, we show that multiple synergistic feedback loops connect back to the transcription factor PPARgamma with different time delays to drive the terminal differentiation of adipocytes, a process critical for our understanding of obesity and metabolic diseases. Together, our study argues that the transition from pre‐adipocytes to terminally differentiated adipocytes is an interconnected single module with multiple positive feedback loops rather than a series of sequential regulatory processes along the path to differentiation.
Novel protease mediated mechanisms promote the spread of cancer cells via the blood circulation
Authors: Hooper John , Yaowu He , Casar Berta , Ying Dong , Wortmann Andreas , Adams Mark , Clements Judith , Quigley James
Published: June 2021

Although the dysfunctional activities of proteases in cancer metastasis have been recognised for some time, the particular mechanisms mediating the roles of these enzymes in the spread of cancer remain poorly defined. Recently we have demonstrated that signals initiated by proteolytic cleavage of cell surface receptors can initiate metastasis promoting responses. One of these receptors is the cell surface glycoprotein CUB domain containing protein 1 (CDCP1). Our data indicate that CDCP1 is cleaved at the cell surface in vitro and in vivo by serine proteases thereby initiating intracellular signalling cascades involving activation and docking to CDCP1 of the kinases Src and PKCδ and downstream activation of Akt. Interestingly, we have shown that this cascade protects cancer cells as they disseminate via blood vessels in vivo and we have identified proteases initiating this protection in model systems. Our findings further demonstrate roles for CDCP1 in cell migration in vitro including its competition as a Src substrate with a critical mediator of cell adhesion, FAK, and its role in migration induced by EGFR signalling. Targeting CDCP1 and its signalling effectors may be a rational approach to treat cancer patients at risk of recurrent disease.

Support: Wesley Research Institute, Australian Research Council, Cancer Council Queensland, National Health and Medical Research Council of Australia
The Role of Shoc2 in Regulating Cell Motility
Authors: Jang Hye In , Jeoung Myoungjun , Galperin Emilia
Published: June 2021

The extracellular‐signal‐regulated kinase 1/2 (ERK1/2) signaling cascade is a fundamental cellular process that orchestrates diverse biological outcomes including cell growth, proliferation, migration, and apoptosis. Mutations of the components in ERK1/2 signaling pathway are often found in cancer cells and tumors. ERK1/2 activity is controlled by scaffold proteins that assemble unique signaling complexes, target multi‐protein signaling modules to certain cellular locations and enhance the activity of ERK1/2 substrates at particular sub‐cellular localizations. Thus, scaffolds deliver signal specificity and determine the biological outputs of the ERK1/2 pathway. Ras‐Raf‐binding scaffold protein, Shoc2, is essential for proper ERK1/2 pathway signaling upon epidermal growth factor receptor (EGFR) activation. Decrease in Shoc2 levels leads to significant reduction in ERK1/2 phosphorylation upon EGF treatment. Here we focus on studying physiological role of ERK1/2 signals transmitted through Shoc2 module. We observed that cells with Shoc2 depleted using lentivirus‐delivered shRNA have higher rates of cell proliferation. We also see that the depletion of Shoc2 results in dramatic decrease in cell migration and adhesion. All together, these results suggest that Shoc2 has an important role in regulating cell motility and may contribute to cancer/tumor development.
Early Intervention by Targeting Inhibitors of Multiple Signal Transduction Pathways in LPS Induced Human PBMCs
Authors: Borkovec Ashley Rose , Koltermann Kayla , Martin Ashley , Mendis Chanaka , Jett Marti
Published: June 2021

Lipopolysaccharide (LPS) is an endotoxin that induces the secretion of pro‐inflammatory cytokines in many cells which can induce septic shock in humans. This project is aimed at developing a rapid diagnostic method to combat the effects of LPS by utilizing signal transduction pathways induced by LPS in Peripheral Blood Mononuclear Cells (PBMC) as a prototype module. A set of LPS induced genes were identified through micro array analysis and common signaling pathways were found. We blocked key components such as JNK and p38 of these pathways that function as pathway inter‐connectors and then evaluated the extent of alterations to the previously identified gene expression patterns. Further investigation of the pathways led to the identification of common components to multiple pathways that can serve as diagnostic markers. Our main objective was to investigate the effect of two inhibitors on the time dependent gene expression pattern and then the impact on components that are indirectly associated with the inhibited signaling pathways. In addition, we also evaluated the specific inhibitors by correlating the observed gene expression pattern to the protein expression using ELISA. We believe the study will allow us to better understand the complex interactions of multiple signal transduction pathways induced by LPS, and how to combat the effects.
Aspirin prevents growth and differentiation of breast cancer cells: lessons from in vitro and in vivo studies
Authors: Maity Gargi , De Archana , Banerjee Snigdha , Das Amlan , Banerjee Sushanta
Published: June 2021

Aspirin, a classical non‐steroidal anti‐inflammatory drug (NSAID) is widely used to reduce pains and fever. Epidemiological and experimental studies suggested that Aspirin use reduces the risk of different cancers including breast cancer and may be used as a chemopreventive agent against breast cancer and other carcinogenesis. These studies have raised the tempting possibility that Aspirin could serve as a preventive medicine for breast cancer. However lack of in‐depth knowledge of the mechanism of action of Aspirin reshapes the debate of risk and benefit of Aspirin in prevention of breast cancer. Our aim is to investigate effects of Aspirin on pathophysiological events like epithelial to mesenchymal transition (EMT), migration, stemness of cell in breast cancer cells. Our studies using in vitro and in vivo tumor xenograft model show a strong beneficial effects of Aspirin in prevention of breast carcinogenesis. We find Aspirin not only prevents breast tumor cell proliferation in vitro and tumor growth in xenograft mouse model, it also significantly inhibits other pathophysiological events in breast cancer such as EMT, cell migration as well as reprogramming of stemness in breast cancer cells. Collectively our studies suggest that intake of an ASPIRIN a day might offer additional avenues for breast cancer prevention and treatment.

(Support: VA Merit Grants ;S. Banerjee and S.K. Banerjee)
A Novel Mechanism of Bortezomib Function in Prostate Cancer Cells
Authors: Manna Subrata , Phyo Sai Aung , Vancura Michelle
Published: June 2021

Proteasome inhibition is a promising therapeutic strategy in a number of human cancers, including the metastatic prostate cancer, one of the most common malignancies in men.

Bortezomib (BZ) is the first approved proteasome inhibitor that has a remarkable anti‐tumor activity in many hematological malignancies. In solid tumors, BZ has been less effective; however, the underlying mechanisms are not fully understood. The rationale behind the BZ development and use was the inhibition of NFκB activity and suppression of NFκB‐dependent proinflammatory and anti‐apoptotic genes. Unexpectedly however, we found that while BZ decreases expression of most NFκB‐regulated genes, it actually increases expression of the pro‐inflammatory and pro‐angiogenic cytokines IL‐6 and IL‐8 in the metastatic prostate cancer PC‐3 cells. The goal of this study was to investigate the mechanisms underlying the BZ‐increased IL‐6 and IL‐8 expression in PC‐3 cells. Our results show that the BZ‐increased IL‐6 and IL‐ 8 expression in PC‐3 cells is mediated by the IKK kinase. In addition, our data indicate that BZ has a previously unrecognized function that consists of increasing the nuclear accumulation and activity of IKKα and IKKβ. Together, our data suggest that a new combination therapy targeting both IKK and proteasome might enhance the BZ effectiveness in the treatment of solid tumors, including the metastatic prostate cancer.
Thoracic Cavity Fluid Accumulation: A Possible Novel Biomarker in Hemodialysis Patients
Authors: Sussman Elizabeth J , Johnston Carol S. , Boren Kenneth , Singh Bhupinder
Published: June 2021

Research shows chronic hemodialysis (HD) patient's hydration state, measured by whole body bioimpedence spectroscopy, is an independent predictor of mortality. Hyperphosphatemia is also independently associated with mortality in HD patients. It has yet to be determined if fluid accumulation, specifically in the thoracic cavity, is correlated to other predictors of mortality, including phosphorus. In this cross‐sectional study, stable HD patient's (n=25, 61.5±3.2y) thoracic cavity fluid accumulation (TCFA) was measured using the ZOE fluid status monitor (normal range: 19–30 ohms, lower values indicate greater fluid accumulation) and correlated to other traditional nutrition markers, including phosphorus, interdialytic weight gain (IDWG), and HD vintage (months). Results showed TCFA and phosphorus negatively correlated (r=−.479, r2=0.23, p=0.021), while TCFA and IDWG, and TCFA and HD vintage trended toward significance (r=−.386, p=0.063 and r= .371, p=0.074, respectively). These results suggest as two independent predictors of mortality (phosphorus and IDWG) increase, a greater TCFA is seen. Alternatively, as HD vintage increases, TCFA decreases. Funding: Academy of Nutrition and Dietetics Foundation

Grant Funding Source: Academy of Nutrition and Dietetics Foundation
Effectiveness of nutrition education and fruit and vegetable consumption on changes in biomarkers of inflammation and oxidative stress among obese adults
Authors: Wagner Meredith G , Rhee Yeong
Published: June 2021

Obesity is concerning because of the numerous health conditions associated with excess weight. Underlying mechanisms contributing to detrimental health outcomes are oxidative stress and inflammation. Fortunately, regulation of oxidative stress and inflammation is possible via antioxidants consumed through a diet adequate in fruits and vegetables. However, consumption of fruits and vegetables is below recommended amounts. This study evaluated the effectiveness of a nutrition education program and provision of fruits and vegetables on consumption of antioxidants and changes in inflammation and oxidative stress biomarkers. Forty‐seven adults (16 men/31 women; 45.9 ± 11.8 y; BMI 32.7 kg/m2) were randomly assigned to one of three intervention groups: control group received no intervention; education group attended weekly nutrition education lessons; fruit and vegetable group attended weekly nutrition education lessons and received one serving of fruits and two servings of vegetables daily for 10 weeks. Fasting blood draws and consumption of fruits, vegetables, and antioxidants from three‐day food records were assessed. While changes in consumption were minimally associated with improvements in biomarkers of inflammation and oxidative stress, adequate and varied consumption of fruits and vegetables is recommended to aid in regulation of inflammation and oxidative stress. Sources of research support: scholarships, department grant
Exploration of non‐nutritional factors associated with stunting in 24 month old children of rural Bangladesh
Authors: Mehra Sucheta , Schulze Kerry Jean , Merrill Rebecca Day , Shaikh Saijuddin , Ali Hasmot , Shamim Abu Ahmed , Wu Lee Shu‐Fune , Christian Parul , West Keith Parker
Published: June 2021

Nutrition interventions in the critical first 2 years of life have had only modest effects on stunting, a length for age Z‐score (LAZ) < ‐ 2, suggesting that non‐nutritional factors contribute to compromised growth. We are assessing gut permeability and environmental exposures at 24 mo of age as potential causes of linear growth deceleration in 180 children of rural Bangladesh, where over half of children are stunted. Data on health, maternal and infant diet, and growth were characterized from the intrauterine period to 24 mo of age in children in the context of a community‐based, randomized trial to assess maternal antenatal micronutrient supplements on birth outcomes. Mean (±SD) LAZ (% stunted) was −1.47±1.2 (29%) at birth (n=178), −1.37±1.19 (22%) at 6 mo (n=169), −1.86±1.12 (42%) at 12 mo (n=162), and −1.97±1.11 (46%) (n=121) at 24 mo, revealing increasingly compromised linear growth after 6 mo, consistent with timing of complementary feeding and enhanced exposure to pathogenic stimuli. Gut permeability assessed by the lactulose:mannitol test; chronic pathogenic exposure assessed by elevated immunoglobulins, cytokines, and acute phase markers; and aflatoxin exposure at 24 mo will be presented. Associations of these factors with LAZ and individual growth trajectories will be explored. Support: Gates Foundation Grant 614, Grand Challenges Exploration
A food addiction scale measurement in two cohorts of middleaged and older women
Authors: Flint Alan John , Gearhardt Ashley , Corbin William , Brownell Kelly , Field Alison , Rimm Eric
Published: June 2021

The authors examined the prevalence and associated characteristics of a food addiction scale measure in a cross‐sectional analysis of 134,175 women participating in two ongoing prospective cohort studies of U.S. nurses. Overall, 7,839 (5.8%) of the women surveyed met the criteria for food addiction as measured by the modified Yale Food Addiction Scale. The prevalence of food addiction was 8.4% in the younger cohort of women aged 45–64 years and 2.7% in the older cohort of women aged 62–87. In the multivariate model, BMI ≥ 35.0 kg/m2 (compared to BMI 18.5–22.9 kg/m2) was associated with food addiction, RR 15.83 (95% CI 12.58–19.91) among the younger cohort of women aged 45–64 years, and RR 18.41 (95% CI 11.63–29.14) among the older cohort of women aged 62–87. Several other demographic characteristics were associated with the food addiction measure in both cohorts of women. For the first time in a large U.S.‐based population of women, the authors have documented the high prevalence of food addiction by a novel measurement scale in middle‐aged and older women. The results may provide insight into the strong association between behavioral attributes of food consumption and the development of obesity.
Effects of high‐fiber snacks on health‐related quality of life in a sample of school‐aged children
Authors: Baker Selena L. , Reidenbach Katherine L. , McCabe Sean D. , Brauchla Mary C. , Kranz Sibylle
Published: June 2021

Up to 10% of U.S. children suffer from chronic constipation, accounting for 25% of referrals to pediatric gastroenterologists. Constipation can lower health‐related quality of life (HRQOL). Dietary fiber reduces the risk for constipation but is under‐consumed in children. We assessed child‐ and parent‐reported pediatric HRQOL in a sample of 7 to11‐year‐olds at baseline of an 8‐week intervention study aimed at increasing high‐fiber snack intake. Children and parents completed the PedsQL at baseline. Response rates were 92.2% (children) and 83.1% (parents). Children were more likely to skip questions while parents were more likely not to respond or to fail to return the survey. Mean total and subscale scores were computed. Children's total score was 81.5±11.8 (n=70, max. score 100), physical subscale score was 87.1±11.5 (n=71) and psychosocial subscale score was 78.4±14 (n=70). Parents’ mean scores were higher, with a total score of 86.5±10.5, physical subscale score of 92.4±12.6 and psychosocial subscale score of 83.3±12.2. The psychosocial score includes 3 subscales: “about my feelings”, “how I get along with others” and “about school”. The correlation between parent‐ and child‐reported total HRQOL was weak (R2=0.0341). Thus, although the PedsQL is a validated tool, our results indicate only a weak association between parents’ and children's estimation of HRQOL. Research supported by the Kellogg Company.
Dietary potassium and sodium impact blood pressure in adolescence
Authors: Buendia Justin Rene Goce , Hasnain Syed Ridda , Bradlee M. Loring , Moore Lynn L
Published: June 2021

Adolescent blood pressure is a strong predictor of adult BP but the role of dietary sodium and potassium on adolescent BP is unclear. Our goal was to estimate effects of dietary sodium, potassium and the ratio of the two on adolescent BP. Data from 2379 girls, initially ages 9–10, and followed 10 years in the National Growth and Health Study, was used. Mean sodium and potassium intakes were 3.1 and 2.0 g respectively from an average of 6.6 sets of 3‐ day diet records. While sodium and potassium intakes were highly correlated (r=0.59), they had opposite BP effects. ANCOVA & repeated measures mixed models were used to estimate mean BP change over 10 yrs and at 18–20 yrs of age, controlling for height, race, TV/video time, activity, total energy, low‐fat dairy, BMI. Adjusted mean BP levels (mean age=18.3 yrs) declined linearly with increasing tertiles of potassium intake (SBP:109.5, 109.1, 108.4 mmHg; DBP:66.2, 65.2, 64.9 mmHg; p‐trend<0.05 for both). BP also declined with increasing tertiles of K:Na ratio (SBP:109.6, 109.5, 108.0 mmHg; DBP:65.9, 65.6, 64.9 mmHg; ns). In longitudinal models, girls with the highest K:Na ratio (>;0.75) & potassium intakes (>;2275 mg) had statistically significantly lower systolic (but not diastolic) BP levels throughout adolescence. Sodium intake had no effect on adolescent BP. This study suggests that dietary potassium may play a more important role than sodium in determining adolescent BP levels.

Grant Funding Source: NIDDK and National Dairy Council
Dairy consumption is inversely associated with the risk of metabolic syndrome in Korean adults
Authors: Kim Jihye
Published: June 2021

This study explored the association between dairy food consumption and the risk of metabolic syndrome in Korean adults. The study sample comprised 4,862 Korean adults (≥ 19 years) who participated in the fifth Korean National Health and Nutrition Examination Surveys. Dairy food consumption was assessed using a food‐frequency questionnaire. Metabolic syndrome was defined according to the joint interim statement of the International Diabetes Federation/American Heart Association. We found that adjusted odds ratios (ORs) for abdominal obesity and high fasting glucose were significantly lower among subjects in the highest (≥ once/day) than in the lowest (none or rarely) category of milk consumption after adjusting for potential risk factors (OR=0.68, 95 % CI: 0.50–0.93, P for trend=0.0314; OR=0.82, 95% CI: 0.65–1.03, P for trend=0.0233). The adjusted ORs for lower HDL cholesterol was 28 % lower among subjects in the highest as compared with subjects in the lowest category of yogurt consumption (OR=0.72, 95 % CI: 0.52–1.00, P for trend=0.0197). Furthermore, higher consumption of milk or yogurt was found to be significantly associated with a lower risk of metabolic syndrome (OR=0.71, 95 % CI: 0.55–0.93, P for trend=0.0066; OR=0.71, 95 % CI: 0.48–1.05, P for trend=0.0067). High intakes of dairy foods may be associated with a lower risk of metabolic syndrome. Supported by Daegu University
Breastfeeding knowledge, attitudes, and intent in a sample of Chinese undergraduate students
Authors: Lou Zixin , Zeng Guo , Huang Lujiao , Liu Fang , Pang Xuehong , Kavanagh Katherine
Published: June 2021

The principle objective of the study was to explore, among Chinese undergraduates, any relationships between breastfeeding (BF) knowledge, attitudes, previous exposures, and intent to breastfeed a future child. A questionnaire relevant to this population was developed and carried out in several undergraduate classes in a major public university located in southwest China. Three hundred and ninety‐four undergraduates completed the questionnaire, with the sample consisting primarily of freshmen and sophomores. Knowledge scores ranged from 1 to 13 (with 13 being the highest possible score), with a mean of 8.3±1.5 (64.0% of the total score). Responses showed that one‐third of the sample disapproved BF in public (32.7%), and another one‐third was neutral to this behavior (32.5%). In addition, 34.3% believed BF to be painful, and 52.2% believed BF would restrict the freedom of mothers. Most students expressed intent to breastfeed a future child (75.0%), though males were significantly more likely to do so than females (81.6% vs. 71.7%, p=0.03). Future BF intent was associated with positive BF attitudes and with having been breastfed as an infant. Results indicate that BF knowledge is at a moderate level in this population, though intent to BF future children is high. Future research is warranted to explore and address the negative views of BF.

Grant Funding Source: The University of Tennessee, Department of Nutrition, the Office of the Dean, and the Office of Research (SARIF Award).
A Study on the diet behaviors of middle school girls in Incheon Korea, according to variables of home environment
Authors: Chung Hyun‐Jung , Lee Jin‐Myung
Published: June 2021

This research was conducted to evaluate the status of dietary behaviors of middle school girls according to variables of home environment. The subjects were 336 students in 1st‐3rd grade of Girls’ middle school located in Incheon. As for status of dietary life, students eat breakfast everyday on a regular basis with mothers staying home (p<0.05). For breakfast types, Korean traditional breakfasts showed the highest rate with significant difference between number of family members (p<0.001). Mother with lower academic background showed higher rate of preparing breakfast (p<0.05). As for lunch, students eat everyday on a regular basis. For dinner, students eat everyday on a regular basis at home with significant difference according to BMI (p<0.01). Mother was reported to prepare dinner and there was significant difference according to number of family (p<0.001), mother's academic background (p<0.01), mother's occupation (p<0.001), and BMI (p<0.05). As a result, the best dietary behavior was found with the number of family members of 4, with mother's age over 46, with mother's academic background below middle school(p<0.05), and when mother's occupation is to run one's own shop. For BMI, students with obesity showed the best dietary behavior.
Consumers¡ perception and response to CSR activities of food companies
Authors: Chung Hyun‐Jung , Lee MiYoung
Published: June 2021

The purpose of this study is 1) to explore consumers¡ perceptions toward different types of CSR(Corporate Social Responsibility) activities for food companies, and 2) to investigate the relationship between consumers¡ perception of food companies¡ CSR activities, and consumers¡ attitudes toward that company and the purchasing intention of a product from that company. Data were collected through a survey with 200 college students living in metropolitan area. The result indicated that there are differences in consumers¡ perceived suitability depending on types of CSR activities of food companies. It is also found that food companies¡ CSR activities were positively affect consumers attitudes to that companies¡ reputation, trust, and preference, and consumers¡ attitude toward CSR activities also positively related to the consumer¡ s purchasing intention of a food product from the company. The results also indicated that there are significant differences in consumers¡ perception and responses to food companies CSR activities based on product type, and consumers¡ knowledge level of social responsibility.
Testing the internal validity of a questionnaire measuring dietary satisfaction through factor analysis
Authors: Wheeler Brooke E. , Hsiao Pao Ying , Durward Carrie M. , Rolls Barbara J. , Nickols‐Richardson Sharon M.
Published: June 2021

Although dietary satisfaction is thought to play an important role in compliance with weight loss interventions, few tools exist to measure this construct. The objective was to test the validity of a previously developed 45‐item dietary satisfaction questionnaire (DSAT) in a sample of premenopausal women with overweight/obesity (n =180; Mean age 34.5 y SD ± 6.9; BMI 30.3, SD ± 3.6) participating in a weight loss intervention. Factor analysis with a Varimax rotation was used to test the validity of the original DSAT. Examination of eigenvalues and a scree plot were used to determine the number of factors to retain. The analysis resulted in 36 items that loaded onto six factors ranging from .316 to .933. Factors were labeled: “Preoccupation with diet”, “Benefits of diet”, “Eating away from home”, “Diet planning”, “Family impact”, and “Financial cost.” A valid dietary satisfaction questionnaire may be a valuable measure of compliance to a prescribed weight loss intervention. This tool also may be useful for tailoring advice to increase dietary satisfaction to maximize weight loss and weight loss maintenance.

Grant Funding Source: N/A
Indiana students in the 2010–11 USDA Fresh Fruit and Vegetable Program (FFVP) increased variety of fruits and vegetables consumed and requests to parents to purchase fruits and vegetables through mediating changes in intention and attitude
Authors: Lin Yi‐Chun , Foland Elizabeth , Bai Yeon , Fly Alyce D.
Published: June 2021

FFVP is a purchase‐support intervention used to increase intake and variety of fruit (F) and vegetable (V). To study the role of mediators on 4 F/V eating behaviors (daily variety of F/V, asking parents to buy F/V), 4th graders in 8 intervention (IN) and 8 control (C) schools (n=1611) completed 58‐item questionnaires about intake, intentions to eat F/V, and, attitude, subjective norms and perceived behavioral control, both prior to and 8 months into intervention. Data were analyzed to determine total effects of the intervention × time interaction on 6 separate situations including, daily variety F/V consumed, asking parents to buy F/V, intention to eat more F/V, with multiple regression. Indirect effects were measured using 10 simple mediation analyses following multiple regressions by product of coefficients. These 10 analyses included 4 paths mediating behaviors and 6 mediating intentions. IN increased daily variety of F (p=0.015) and V (p=0.017), more frequently asked parents to buy F (p=0.002), and intended to eat more F (p=0.004) & V (p=0.009) compared to C. IN improved global F attitudes (p=0.016) but only one attitude toward eating V (p=0.017). Effects of intervention on eating more types of F/V and asking parent to buy F were mediated by intention. Intentions to eat more F/V were mediated by attitude. FFVP may have improved F and V eating behaviors by indirect influences from intention and attitude.
The tumor suppressor protein PDCD4 is a critical regulator of muscle cell differentiation
Authors: Adegoke Olasunkanmi John , Abdullahi Abdikarim , Gilad Amir , Maeda Naomi
Published: June 2021

The mammalian target of rapamycin complex 1/S6 ribosomal protein kinase 1 (mTORC1/S6K1) pathway is a critical regulator of mRNA translation and skeletal muscle mass. It does this in part by inhibiting the tumor suppressor protein, programmed cell death 4 (PDCD4). In C2C12 and L6 muscle cells, we showed that PDCD4 abundance was high on day 1 and then decreased as myoblasts differentiated into myotubes (p<0.05). siRNA‐mediated knockdown of S6K1 reversed the decrease in PDCD4 abundance and significantly decreased myosin heavy chain 1 (MHC 1) protein abundance, suggesting that PDCD4 regulation was vital for differentiation. Indeed, cells depleted of PDCD4 had reduced MHC abundance, showed delayed myoblast fusion and abnormal myotube formation. On days 3 and 4 of differentiation, myotubes depleted of PDCD4 showed 40–60% reductions in myotube protein synthesis. This study unravels a link between PDCD4 and muscle cell differentiation, and suggests that this mTORC1/S6K1 substrate may be of therapeutic significance for muscle recovery following injury or atrophy. Funded by NSERC.
Manganese Neurotoxicity is Enhanced by Iron Depletion.
Authors: Seo Young Ah , Li Yuan , Wessling‐Resnick Marianne
Published: June 2021

Chronic exposure to manganese (Mn) results in neurobehavioral problems, particularly in children, but the molecular mechanisms are unknown. Accumulating evidence suggests that endoplasmic reticulum (ER) stress plays a significant role in neurodegenerative diseases. ER stress and the unfolded protein response (UPR) lead to cell apoptosis. Using dopaminergic SH‐SY5Y cells, we have characterized Mn cytotoxicity. Mn‐induced apoptosis was potentiated by iron depletion upon cell treatment with desferoxamine (DFO), a potent iron chelator. Mn exposure induced ER stress genes, including ER chaperone GRP94 and the pro‐apoptotic CHOP protein, with activation of ER resident caspase‐12. The important effector caspase‐3 was also activated. All of the Mn‐induced responses were enhanced by DFO treatment. To study Mn intoxication in vivo, iron‐deficient and control rats were intranasally instilled with 60 mg MnCl2/kg across 3 weeks. TUNEL staining of olfactory tissue confirmed that Mn induced apoptosis through a pathway potentiated by iron depletion. Taken together, our data reveal that Mn induces neuronal cell death through ER stress and the UPR response pathway and that this apoptotic effect is potentiated by iron deficiency. These studies provide insight into mechanisms of Mn neurotoxicity and raise awareness of the potential susceptibility of iron‐deficient children exposed to high Mn.

Grant Funding Source: National Institute of Health
Seven Mineral Intakes and Their Relations with Blood Pressure and Blood Lipids in Healthy Adults with Self‐Selected Diet
Authors: Choi Mi‐Kyeong , Kim Eun‐Jin , Kim Mi‐Hyun , Kang Myung‐Hwa
Published: June 2021

The purpose of this study is to evaluate the dietary intake of Ca, P, Mg, Fe, Zn, Cu, and Mn and investigate their correlation with blood pressure and blood lipids. Targeting 258 healthy men and women, blood pressure was measured and blood samples were collected to analyze serum lipids, and then the intake of 7 minerals was assessed through a food intake survey for 3 days using a 24‐ hour recall method. The average age of the men and women was 49.6 and 49.2 respectively. The daily energy intake of the men was 1830.6 kcal which was significantly higher than that of women, 1476.2 kcal (p<0.001). The mineral intake of the subjects was as follows: 451.0 mg/d for Ca, 915.2 mg/d for P, 279.2 mg/d for Mg, 12.6 mg/d for Fe, 8.3 mg/d for Zn, 1.2 mg/d for Cu, and 4.2 mg/d for Mn. These accounted for 63.8%, 130.8%, 90.7%, 129.8%, 97.5%, 154.5%, and 113.5% of adequate intake or the recommended intake of each mineral, respectively. Subjects who did not satisfy the estimated average requirement were 74.0% for Ca, 63.2% for Mg, and 41.9% for Zn. After adjusting for age, sex, BMI and energy intake, Mg intake had a negative correlation with SBP, and Cu intake had a significant negative correlation with SBP and DBP. Also, Mn intake was negatively correlated with DBP, serum total cholesterol and triglycerides. Thus, it is concluded that the dietary intake of Mg, Cu and Mn may play an important role in controlling blood pressure and lipids.
Vitamin D status is related to intramyocellular lipid in older adults
Authors: Redzic Maja , Powell David K , Thomas D. Travis
Published: June 2021

Previous work has recognized that vitamin D status is inversely associated with extramyocellular lipid (EMCL). However, the relationship between vitamin D and intramyocellular lipid (IMCL) has not been established, particularly in aged subjects. Since IMCL and vitamin D status are both associated with muscle function, our objective was to further examine these relationships in an elderly sample. Measures of 25(OH)D were obtained in 13 adults between the ages of 65–78. Lateral and medial gastrocnemius IMCL and EMCL were measured with magnetic resonance spectroscopy and fat segmentation. A lifestyle questionnaire assessed physical activity level. Strength (1‐rep max) and physical performance measures (step test/gait speed) were performed. Mean body mass index (BMI) was 26.5±1.1kg/m2 with a range of 19.5 to 33.7kg/m2. Mean 25(OH)D was 37.9±4.1ng/mL with a range of 19 to 68ng/mL. IMCL to water ratio was 0.53±0.06. 25(OH)D correlated with IMCL (r=0.39; p=0.02), but not with EMCL (r=0.01; p=0.94). IMCL was not correlated with BMI (r=0.03; p=0.59) or different by physical activity level (p=0.37). Strength and performance were not correlated with IMCL (p>;0.4), EMCL (p>;0.7) or 25(OH)D (p>;0.09). These data suggest that vitamin D status is positively associated with IMCL. Future research should examine the vitamin D and muscle lipid relationship to determine if vitamin D contributes to [IMCL]/[EMCL] repartitioning.