bluuebunny/crossref_metadata_2025 huggingface dataset:
ST6Gal‐I‐mediated sialylation of Fas and TNFR1 controls receptor localization and apoptotic signaling
Authors: Schultz Matthew J , Swindall Amanda F , Liu Zhongyu , Bellis Susan L
Published: June 2021

The Fas and TNFR1 death receptors regulate the balance between cell survival and cell death. The activation of Fas and TNFR1 stimulates signaling pathways promoting either cell survival/proliferation or apoptosis, although the mechanisms regulating these diverse pathways are not well‐understood. It has been suggested that surface localized Fas and TNFR1 initiate survival signaling through NFkB and MAPKs, whereas receptor internalization is required for caspase activation and apoptosis. Studies from our group now suggest that differential sialylation of Fas and TNFR1 plays a key role in regulating receptor surface localization, and correspondingly, cell fate. The ST6Gal‐I sialyltransferase, which is dynamically regulated in immune and cancer cells, adds an alpha 2–6 linked sialic acid to Fas and TNFR1. The addition of this sugar inhibits receptor internalization following ligand‐induced activation, leading in turn to a blockade in formation of the Death Inducing Signaling Complex and activation of apoptotic caspases. However, ST6Gal‐I‐mediated sialylation of Fas and TNFR1 does not simply shut off apoptosis, but also amplifies ligand‐induced activation of MAPKs and NFkB. These collective results highlight a new glycosylation‐dependent mechanism that regulates Fas and TNFR1‐dependent signaling to control the switch between cell survival and cell death.
Glycoprotein Applications using Near Infrared Detection
Authors: Urlacher Teresa , Cheung Lael , Wang Ying , Xing Kuiyi , Kundu Kousik , Volcheck William , Padhye Nisha
Published: June 2021

We describe a variety of applications and reagents for glycoprotein detection using a near infrared detection system. Near infrared fluorescence detection avoids background from autofluorescent biological materials such as cellular components, buffers and chemicals used for cellular treatment, and solid support surfaces such as nitrocellulose and PVDF membranes. New reagents and applications for glycoprotein analysis include a near infrared total glycoprotein stain that provides specificity and sensitivity, chemoselective labeling using azadibenzocyclooctyne (DBCO), glycoprofiling by Western blotting, lectin blotting or lectin arrays, and a novel chemifluorescent substrate that improves sensitivity of Western blotting up to 32‐fold. Altogether these methods provide an optimal and sensitive platform for detecting a wide variety of glycoprotein interactions and modifications.
Balancing life with glycoconjugates: unfolded protein response targets proteome for anti‐angiogenic action of tunicamycin
Authors: Baksi Krishna , Banerjee Aditi , Santiago Jesus , Longas Maria O , Kotapati Ashok , Prasad Kilari PVRK , Banerjee Dipak K
Published: June 2021

Angiognesis (proliferation and differentiation of capillary endothelial cells) are essential for normal growth and development as well as for solid tumor progression and metastasis. Asparagine‐linked (N‐linked) glycoproteins play an important role in angiogenesis; “hybrid” but not “complex” type glycans are required for capillary tube formation. Our objective is to understand the dynamic relationship between protein N‐glycosylation and angiogenesis. Using a protein N‐glycosylation inhibitor tunicamycin, we establish that angiogenesis inhibition in humanized breast tumor is due to ER stress‐mediated unfolded protein response (upr). For further evaluation, the proteome was analyzed. The Raman Spectroscopy focused on bands that are characteristics of proteins and originate from C=O stretching vibrations of mono‐substituted amides. In tunicamycin‐treated cells the area under these bands are decreased: at 1672 cm−1 by 41.85% at 3 h and 55.39% at 12 h; at 1684 cm−1 by 20.63% at 3 h and 40.08% at 12 h; and at 1994 cm−1 by 33.33% at 3 h and 32.92% at 12 h, respectively. Thus, in the presence of tunicamycin, newly synthesized protein chains fail to arrange properly into their final secondary and/or tertiary structures, and the random coils they form undergo further degradation. Supported in part by grants from Susan G. Komen for the Cure BCTR0600582 (DKB) and NIH/NIMHD 8G12MD007583 (KB).
Identification of tomosyn as a new downstream target of Akt
Authors: Nagano Koki , Takeuchi Hiroshi , Sugiyama Goro , Gao Jing , Otani Takahito , Hirata Masato
Published: June 2021

Insulin stimulates glucose uptake into skeletal muscle and adipose tissues by increasing the available number of glucose transporter (GLUT) 4 on the cell surface. GLUT4‐loaded vesicles are targeted to plasma membrane from the intracellular reservoir through multiple trafficking steps that are regulated by protein kinase Akt. Although many clues that regulate targeting and docking of GLUT4‐vesicles to the plasma membrane had been identified, it is still largely unknown how the membrane fusion is promoted by insulin. Thus, we tried to identify a new target of Akt which is responsible for up‐regulation of SNARE‐mediated membrane fusion in insulin‐stimulated cell.

We first searched for proteins bearing the recognized motif to be phosphorylated by Akt on databases. Among them, an Akt‐site was highly conserved at Ser‐783 in rat tomosyn, a SNARE binding protein, which might be involved in GLUT4 trafficking. Both Akt1 and Akt2 phosphorylated recombinant tomosyn in vitro, and the phosphorylation was diminished by replacing Ser‐783 with Ala (S783A). Protein kinase A (PKA) also phosphorylated tomosyn, but S783 is not the residue phosphorylated by PKA. The interaction of tomosyn and syntaxin 4 was modulated by the phosphorylation. The results suggest that tomosyn would be involved in insulin‐triggered membrane fusion between docked GLUT4 vesicle and the target plasma membrane.
Elucidation of structural determinants of polycystin‐1 interaction with Gα12
Authors: Snelson Mark Thomas , Cavagnini Kyle S , Denker Bradley M. , Meigs Thomas E.
Published: June 2021

Autosomal dominant polycystic kidney disease is a widespread malady in which mutations in the cell surface protein polycystin‐1 (PC1) are found in nearly 85% of cases. PC1 interaction with the heterotrimeric G protein Gα12 has been implicated as a regulator of Gα12‐mediated events that include apoptosis. The C‐terminal, cytoplasmic tail of PC1 has been shown to interact with several G protein α‐subunits, and a 20 amino acid G protein binding sequence (GPS) resides within this cytoplasmic domain. Our previous work revealed a 74 amino acid region of the PC1 tail, encompassing the GPS, to be necessary for Gα12 binding. To identify specific PC1 residues involved in Gα12 interaction, we have engineered several single and multiple charge‐substitution mutations within the GPS. Co‐precipitation assays have revealed several PC1 residues as potential determinants of Gα12 binding. Furthermore, a truncation mutant of PC1 downstream of the GPS, previously linked to polycystic kidney disease, shows a near‐complete loss of Gα12 binding. Our findings from apoptosis assays and transcriptional activation assays suggest that direct interaction between PC1 and Gα12 is essential for the ability of PC1 to negatively regulate Gα12‐mediated signaling. We acknowledge support from the UNC‐Asheville Undergraduate Research Program (MTS and KSC), Harvard Polycystic Kidney Center (BMD), and Lineberger Comprehensive Cancer Center (TEM).
Impaired antiviral response due to up‐regulated HSCARG and down‐regulated NF‐κB signaling by HCoV 229E infection in G6PD‐knockdown A549 cells
Authors: Wu Yi‐Hsuan , Ho Hung‐Yao , Lin Hsin‐Ru , Yang Hung‐Chi , Cheng Mei‐Ling , Chiu Daniel Tsun‐Yee
Published: June 2021

Glucose‐6‐phosphate dehydrogenase (G6PD) provides NADPH as reducing power for maintenance of the cellular redox status. Previously, we have reported that G6PD‐deficient cells are more susceptible to viral infection, however, the mechanism remains elusive. Toward this end, we analyzed the antiviral response upon HCoV 229E infection in A549 and MRC‐5 cells and found that the expression of TNFα, OAS and MX‐1 genes were up‐regulated at the early stage of viral infection. We further investigated the mRNA expression of OAS and MX‐1 was slightly decreased in G6PD‐knockdown cells. In addition, the expression of antiviral cytokine, TNFα, was lower in G6PD‐knockdown than that in control cells. Interestingly, the reduced antiviral responses in G6PD‐knockdown cells could be restored by complementation of G6PD activity. In addition, reduced IκB degradation and decreased NFκB activation were observed in G6PD‐knockdown A549 cells when compared with that of control. Furthermore, we found that HSCARG protein which was the NADPH sensor and could hamper NFκB activation was up‐regulated in G6PD‐knockdown A549 cells leading to impaired antiviral gene expression. All in all, these data support the notion that enhanced susceptibility to viral infection in G6PD‐knockdown cells is due to impaired NFκB signaling by redox imbalance‐induced increasing HSCARG expression and adversely affects the antiviral response.
ADAM12: A Novel Mediator of Tumor Angiogenesis
Authors: Roy Roopali , Moses Marsha
Published: June 2021

We have previously demonstrated that urinary ADAM12 (a disintegrin and metalloprotease) is predictive of breast cancer status and stage and that expression of ADAM12 in breast tumors results in increased tumor take, tumor size and metastasis. ADAM12 expression is upregulated in the vessels of aggressive human breast tumors as compared to those of normal adjacent tissue. ADAM12‐overexpressing breast tumors also displayed a higher microvascular density. The goal of this study was to determine the mechanism by which ADAM12 may regulate tumor angiogenesis. Increased ADAM12 expression in breast tumors resulted in a significant upregulation of proangiogenic factors such as VEGFA, MMP‐9, and MCP‐1 while antiangiogenic factors such as TIMP‐1 and Thrombospondin 1 were downregulated. Conditioned media from ADAM12‐expressing tumor cells promoted human endothelial cell (EC) migration and tube formation. EC treated with recombinant ADAM12 showed significantly increased migration, tube formation and adhesion to matrix. Our findings suggest that elevated ADAM12 expression in tumor cells induces a proangiogenic/proinflammatory microenvironment which in turn facilitates angiogenesis and tumor growth. This suggests that the inhibition of ADAM12 may represent a novel strategy to target tumor angiogenesis. [Supported by NIH PO1 CA045548, The Breast Cancer Research Foundation and The Simeon J. Fortin Foundation]
Differential Expression of Matrix Metalloproteinases (MMPs) in Lung Cancer Metastasis
Authors: Hoerter Jacob Edward , Bodduluri Haribabu , Sharma Rajesh
Published: June 2021

Metastasis accounts for most cancer related deaths. The common metastasis models utilize intravenous injection of tumor cells, bypassing the egression of malignant cells. We developed a unique metastasis model by in vivo passaging the Lewis lung carcinoma (3LL) cells and maintaining them in vivo with 7–11 days of intermittent culture. When injected subcutaneously, parental 3LL cells have minimal metastasis, while in vivo passaged 3LL cells (p‐ 3LL) show robust metastasis. To determine the differences between metastatic p‐3LL versus non‐metastatic 3LL, we compared the gene expression profiles by microarray analysis of RNA from these cells as well as the primary tumors from each. The array analysis revealed alteration in the expression of numerous genes previously known to be associated with tumor metastasis. The data also revealed several novel markers associated with increased metastasis including enhanced expression of two matrix metalloproteinases (MMPs), MMP‐9 and MMP‐12, and the decreased expression of MMP‐2. Given the role of MMPs in the remodeling of the extracellular matrix and cell motility, we further investigated the altered RNA and protein expression of MMPs in p‐3LLs and their tumors by real time PCR and Western blot analysis. Together, these suggest that these three MMPs may play an important role in lung cancer metastasis.
Aerobic exercise during pregnancy increases antioxidant status in nulliparous women
Authors: Ramírez‐Vélez Robinson
Published: June 2021

Aim

To determine the effects of exercise in the second half of pregnancy on antioxidant status in pregnant women.

Methods

This was clinical trial of 20 primigravid women between 16 and 20 weeks’ gestation. Antioxidant status was measured using the antioxidant assay kit in samples of the maternal peripheral blood serum at baseline, at the end of the three‐month intervention period and cord blood at 15 min of delivery.

Results

At 3 months, the supervised aerobic exercise program, showed slightly higher values for antioxidant status in maternal peripheral blood serum in the experimental group compared to the control group, (0.58±0.24mM) vs. (0.28±0.06mM), respectively(p=0.25). Two‐way ANOVA analysis revealed that umbilical cord blood antioxidant status was significantly higher in the exercise group at the end of the intervention (p<0.001, F=8.09).

Conclusions

This study showed that 12 weeks of aerobic exercise increased antioxidant status in nulliparous women. It has been suggested that regular exercise is associated with beneficial effects on the incidence of preeclampsia because of its antioxidant effects
Relationship between blood pressure and serum 25‐ hydroxyvitamin D among a young multi‐ethnic group living in South Florida
Authors: Podesta Cinthia , Ajabshir Sahar , Exebio Joel C , Zarini Gustavo G , Podesta Rodrigo , Huffman Fatma G
Published: June 2021

The aim of this cross‐sectional study was to investigate the relationship between blood pressure (BP) and serum 25‐ hydroxyvitamin D [25(OH)D] among a young multi‐ethnic group (N=81) living in South Florida. Participants included males (n=42) and females (n=39). A BP automated monitor with an adult size cuff was used to take two BP measures. Fasting serum 25(OH)D were determined by ELISA. Statistical analyses included t‐test and linear regression. The systolic blood pressure (SBP) was higher among males (115.1 ± 12.5) than females (101.9 ± 11.8) (P=<0.001). One unit increase in serum 25(OH)D decreased diastolic blood pressure (DBP) by 0.350 units (P=0.018) when controlling for body mass index (BMI), age, education, race and years in the US. The results of this study suggested that there is an inverse relationship between serum 25(OH)D and DBP among males in this young multi‐ethnic group.
Comparison of stearic acid versus monounsaturated fatty acids on hemostatic factors in healthy men fed controlled diets
Authors: Gebauer Sarah K , Tracy Russel P , Baer David J
Published: June 2021

Evidence suggests that stearic acid (STE) differentially affects lipoprotein risk factors compared to other saturated fatty acids (SFA). When compared to cholesterol‐raising SFA, STE lowers LDL‐cholesterol (LDL‐C) and has a neutral effect on HDL‐C, thus lowering the ratio of total cholesterol to HDL‐C. The impact of STE on other markers of cardiovascular disease risk is unclear. The 2010 Report of the Dietary Guidelines Advisory Committee specifically addresses the need for more research on other metabolic effects of STE, including coagulation, particularly when replaced for unsaturated fatty acids in the diet. In a randomized crossover study, 50 men consumed 6 controlled diets for 5 wk each [39% en from fat, 15% en from protein, and 46% en from carbohydrate (CHO)]. Fat or fatty acids (8%) was replaced across diets as follows: CHO (control), oleic acid (OL), STE, TFA, TFA/STE (4% of en each), and 12:0 –16:0 SFA. After consuming the STE diet, there were no differences in factor VIIc, plasminogen activator inhibitor‐1 (PAI‐1), and plasmin alpha‐2‐antiplasmin complex, when compared to the CHO control diet (P >; 0.05). The OL diet increased factor VIIc and PAI‐1 when compared to control (P ≤ 0.05). There were no differences between the OL and STE diets for these measures (P >; 0.05). In conclusion, STE and OL similarly impacted markers of hemostasis and fibrinolysis in healthy men, within the context of a highly‐controlled diet.
Effect of tree nuts on features of the metabolic syndrome: A systematic review and meta‐analysis of randomized controlled dietary trials
Authors: Mejia Sonia Blanco , Sievenpiper John L. , de Souza Russell J , Augustin Livia S , Viguiliouk Effie , Ha Vanessa , Mirrahimi Arash , Chiavaroli Laura , Cozma Adrian I , Jenkins David J A , Kendall Cyril W C
Published: June 2021

Objective

To assess the effect of tree nuts on features of the metabolic syndrome (MetS), we conducted a systematic review and meta‐analysis of randomized dietary trials.

Methods

We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library (through May 25, 2012). We included relevant randomized dietary trials of ≥ 3 weeks reporting all 5 features of MetS (waist circumference, fasting glucose, triglycerides, HDL‐cholesterol [HDL‐C], blood pressure [BP]). Two independent reviewers extracted all relevant data. Data were pooled using the generic inverse variance method and expressed as mean differences (MD) with 95% CI. Heterogeneity was assessed by Cochran's Q and quantified by I2. Study quality was assessed by the Heyland score.

Results

7 trials (n=1018) met the eligibility criteria. Diets high in tree nuts lowered triglycerides compared with control diets low in tree nuts (MD = −0.09 mmol/L [95% CI, −0.17, −0.01]). There was no effect on waist circumference, HDL‐C, BP, and fasting glucose, with evidence of heterogeneity in all analyses.

Limitations

Most of the trials were of short duration (<12 months) and of poor quality.

Conclusion

Pooled analyses show that diets high in tree nuts lower triglycerides. Longer and higher quality trials are warranted. Clinicaltrials.gov identifier: NCT01630980

Funding source: International Nut Council
Low Glycemic Index Diets on Long‐term Blood Pressure Control: A Systematic Review and Meta‐analysis
Authors: Mirrahimi Arash , Reiser Erika , Chiavaroli Laura , Sievenepiper John L , de Souza Russell J , Augustin Livia SA , Beyene Joseph , Kendall Cyril WC , Jenkins David JA
Published: June 2021

OBJECTIVES

We conducted a systematic review and meta‐analysis to assess effectiveness of low GI diets on blood pressure (BP) in the long‐term.

METHODS

We searched MEDLINE, EMBASE, and the Cochrane Register of Clinical Trials for clinical trials, 3 months or longer. Cochrane guidelines and the PRISMA methodologies were used. Results were pooled in Review Manager under generic inverse variance methods with random effects models and expressed as Mean Difference (MD) with 95% CI.

RESULTS

1290 reports were identified with 9 trials meeting eligibility criteria (7 parallel, 2 crossovers). 7 trials reported Systolic BP (SBP) (n=666, average duration= 27.7 weeks) while 6 had Diastolic BP (DBP) data (n=563, average duration= 23.2 weeks). The pooled effect of low GI diets was −0.17mmHg (95%CI: −1.07,0.74) for SBP and −2.26mmHg (95%CI: −4.17, − 0.35) for DBP, with significant heterogeneity for both (I2>;86%, P<0.00001).

CONCLUSION

Low GI diets can lower DBP in T2D in the long‐term.

Study Supported by Barilla
The Association Between Heavy Metals in Food and Alzheimer's Disease in Korean Elderly People
Authors: Jang Mijin , Kim Seong‐Ah , Park Eun Young , Lee Kyung Youn , Shin Sangah , Kim Ji Eun , Joung Hyojee
Published: June 2021

This study was to investigate the association of dietary heavy metal exposure with Alzheimer′s disease (AD) among elderly people (89 dementia patients and 118 normal) recruited from General Hospital and Alzheimer Center in Seoul, Korea in 2011. AD was diagnosed by a psychiatrist based on the criteria recommended by Diagnostic and Statistical manual of Mental Disorders, 4th edition and the National Institute of Neurological and Communicative Disorders and Stroke‐Alzheimer′s Disease and related Disorders Association. A questionnaire was administered for general characteristics and dietary intake was obtained using 3‐day food records. Blood samples were taken to evaluate the heavy metal exposure levels of cadmium, lead, mercury and arsenic; all of which are highly attainable through food consumption. The AD group, which consumed more fish compared to the normal group (p=0.0444), was associated with an increased risk of AD (OR=2.69, 95% CI 1.03–7.04). We also found that subjects who consumed more fish was associated with an increased risk of high serum cadmium level (OR=2.59, 95% CI 1.03–6.54). Other than cadmium however, lead, mercury, and arsenic has no statistically significant differences in both groups. These findings suggest that people who have higher cadmium exposure level from fish consumption may have increased risk of AD. (This work was supported by the KFDA (11162 hazardous material 701)).
Changes in plasma citrulline concentration among young Malian children with moderate acute malnutrition following a 12‐week dietary intervention
Authors: McDonald Christine , Ackatia‐Armah Robert , Kellogg Mark , Erhardt Juergen G. , Doumbia Seydou , Brown Kenneth H. , Duggan Christopher
Published: June 2021

Background

The amino acid citrulline (Cit) is a biomarker of enterocyte mass and may be useful in assessing intestinal absorptive capacity of undernourished children in developing countries.

Objective

To evaluate changes in plasma Cit in Malian children aged 6–35 months with non‐edematous, moderate acute malnutrition (MAM) before and after nutritional rehabilitation.

Methods

Plasma Cit was measured using ultra performance liquid chromatography and mass spectrometry in 128 children (mean age 15.5 mo) enrolled in a trial that provided 500 kcal/d of supplementary food for 12 wks.

Results

At baseline, the mean weight‐for‐height Z (WHZ), height‐for‐ age Z, mid‐upper arm circumference (MUAC), C‐reactive protein (CRP), and plasma Cit concentration were −2.22, −2.16, 12.1 cm, 7.7 mg/L and 12.3 μmol/L, respectively. At 12 wks, mean ± SD Cit increased to 14.3 ± 5.8 μmol/L (p<0.0001). Mean change in plasma Cit was greater among the 88 children who recovered from MAM vs. the 40 who did not (2.7 ± 5.2 μmol/L vs. 0.6 ± 4.8 μmol/L, p=0.03). After controlling for age, sex, baseline CRP and Cit, a 1 μmol/L increase in Cit was associated with increases of 0.037 in WHZ (p=0.005) and 0.029 in MUAC (p=0.04).

Conclusions

Cit increased with gains in WHZ and MUAC during nutritional rehabilitation and may reflect an improved ability to absorb essential nutrients.
ProPAN 2.0 (Process for the Promotion of Child Feeding): a Tool for Infant and Young Child Feeding Programming
Authors: Luttter Chessa , Mir Roger , Pachon Helena , Cheung Edith , Sullivan Kevin , Creed‐Kanashiro Hillary , Panjwani Anita , Escobar Jessica , Alam Khurshid
Published: June 2021

Setting‐specific program guidance on infant and young child feeding, particularly complementary feeding continues to be a challenge. To address this, we developed ProPAN, a step‐by‐step tool aimed at ministries of health, NGOs and international organizations. ProPAN consists of a field manual and software based on Epi Info™ for data entry and analysis. Its features include 1) A process for identifying specific nutritional and dietary problems and understanding the context in which these occur; 2) A method for identifying, ranking and selecting practices that are practical, feasible and acceptable; 3) Electronic templates for rapid data collection, and software for statistical analysis and standardized reports; 4) Joint consideration of breastfeeding and complementary feeding; 5) Integration of quantitative and qualitative methods and instructions for their analysis; and, 6) Guidance on how to convert data into an implementable program. ProPAN 2.0 incorporates the WHO Child Growth Standards, WHO/UNICEF Infant and Young Child Feeding Indicators, a method to measure responsive feeding, questions on HIV and infant feeding, MUAC for use in emergency settings, and outputs to use with WHO's Optifood program. The updated version is based on lessons learned from global implementation. Developed by PAHO/WHO and UNICEF with support from the US CDC and Emory University, ProPAN 2.0 is freely available in English, French and Spanish at www.paho.org/ProPAN. This work was funded in part by GAIN.
Sustainability of food‐security policies during presidential transitions: Framework integrating socio‐political and nutritional sciences
Authors: Escobar‐Alegría Jessica L , Frongillo Edward A
Published: June 2021

Countries committed to providing food security for their citizens face the challenge of implementing policies that have long‐term outcomes. These efforts require commitment, multi‐sector collaboration, financing mechanisms, and capacity development of actors that take time across multiple presidential administrations. This work aimed to develop a conceptual framework for the study of the sustainability of food‐security policies that is grounded in the socio‐political and nutritional sciences. An extensive document review was made of the existing evidence‐based actions to improve food security and the factors that can influence officials’ interest in food security when deciding on agenda setting and commitment within the context of presidential transitions. The framework developed consists of 1) four dimensions of effective actions in which that a new presidential administration can confidently invest, 2) the specific factors related to the institutional environment and the actors for giving priority to the sustainability of food‐security policies, and 3) the context of three phases of a presidential transition (i.e., political campaign, election of new officials, and taking of office of the new administration). This framework provides the conceptual elements for studying sustainability of food‐security policies to better inform joint efforts between nutritionists and policy makers.
Implausible energy intake reporting in overweight women throughout a weight loss trial
Authors: Rodriguez‐Ramirez Sonia , Mendez Michelle A. , Hernandez‐Cordero Sonia , de Cossío Teresa González , Popkin Barry M.
Published: June 2021

Research suggests implausible energy intake reporting increases during weight loss trials, but estimates that ignore energy deficits linked to weight loss may be inflated. We identified implausible reporters in a weight loss trial incorporating measured weight changes. 240 women in Cuernavaca, Mexico were enrolled in a randomized weight loss trial with two arms: dietary counseling only and counseling plus provision of bottled drinking water. Women were 18–45y, with BMIs >;25kg/m2, no chronic diseases, and baseline intakes of sugar sweetened beverages ≥250 kcals/day. Measures were obtained at baseline, 3, 6, and 9 mos. Implausible reporting was identified by the disparity between reported energy intakes (EIs) vs. predicted energy requirements (pER) from doubly‐labeled water equations adjusted for energy deficits based on weight changes and TEE (actigraph). Implausible EIs were defined as intakes exceeding estimated ±1.5 SD limits around pERs. The baseline prevalence of underreporting was 10.8%, increasing to 31.3–35.5% post‐intervention, lower than estimates of 41.3–45.0% which overlooked weight changes. Underreporters had higher baseline BMIs than those with plausible intakes. Underreporting adjustment enhanced diet‐weight loss associations. Underreporting was prevalent even after accounting for weight changes, and should be considered when analyzing dietary changes patterns and weight loss.

Funded by: Danone Research, UNC‐CH and NIPH
Milk intake is associated with lower risk of hip fracture in older men & women: the Framingham Original Cohort
Authors: Sahni Shivani , Tucker Katherine L. , Kiel Douglas P. , Quach Lien , Casey Virginia , Hannan Marian T.
Published: June 2021

Objective

Health effects of dairy foods may be due to more than a single nutrient. We evaluated association of milk, yogurt, cheese, cream & total dairy intakes with incident hip fracture over a 20‐y follow‐up in the Framingham Original Cohort.

Methods

802 men & women completed an FFQ at the baseline (1988–89) and were followed for hip fracture until 2008. We used Cox‐proportional hazards regression to estimate Hazard Ratios (HR) by tertiles of energy adjusted dairy intake (serv/wk) adjusting for age, weight, height, sex, energy intake, current smoking, calcium & vitamin D supplement use.

Results

Mean age was 77y (SD: 4.9, range: 28–92). 104 hip fractures occurred over the follow‐up time. Mean ± SD (serv/wk) of dairy intakes at baseline were: milk 6.0 ± 6.5, yogurt 0.4 ± 1.4, cheese 2.6 ± 3.0, & cream 3.4 ± 5.0. Participants in the higher tertiles (T2–T3) of milk intake [HR (95%CI): T3: 0.61 (0.38–0.99), T2: 0.62 (0.39–1.00)] had lower risk of hip fracture than those in the lowest tertile (P: T3 vs T1: 0.04, T2 vs. T1: 0.05; trend: 0.04). Participants in the highest tertile (T3) of total dairy intake [HR (95%CI): T3: 0.64 (0.39–1.07), T2: 0.98 (0.61–1.54)] tended to have lower risk of hip fracture than those in the lowest tertile (P: T3 vs. T1: 0.09, trend: 0.10). No significant associations were seen for other dairy foods (P trend range: 0.40–0.81).

Conclusion

These results suggest a protective effect of milk, but not of other dairy foods, against fracture risk in older adults. Some foods, particularly yogurt, were consumed in small amounts with limited variability, making it difficult to see an effect.

Funding support: NIH AR # 053205; AR/AG41398 & Framingham Heart Study (N01‐HC‐25195) and General Mills Bell Institute of Health and Nutrition
Comparing Children's Fruit and Vegetable Preferences Using a Pictorial Tool Versus a Tasting Assessment
Authors: Spangler Hillary Beth , Carraway‐Stage Virginia , Borges Michelle , Goodell L. Suzanne
Published: June 2021

Research suggests that fruit and vegetable (FV) preferences have the greatest impact on FV intake. The purpose of this study was to determine the correlation between children's fruit and vegetable preferences assessed by an electronic, pictorial tool and preferences assessed by a “taste and rate” (T&R) assessment. Participants were children, 3–5 years old, (n=57) enrolled in Head Start Centers. A high quality pictorial tool with 20 photographs of fruits and vegetables (13 whole and 7 transformed forms) was compared against the T&R assessment. The T&R assessed 13 different fruits and vegetables. The pictorial tool measurement demonstrated strong internal reliability (alpha=0.80). Concurrent validity outcomes were weak to moderate (rs=−0.25–0.26). Preference responses appeared to be more stable within the pictorial measure (i.e. transformed versus whole FV photographs) than between measures. Preliminary evidence suggests pictorial FV methods may be useful for nutrition educators when establishing baseline preferences among young children, yet further research is needed. In the future, researchers should investigate the viability of a tool that can assess child fruit and vegetable preferences using predictive validity approach.
Improving Periconceptional Health among WIC Participants through the Prevention of Excessive Gestational Weight Gain: From Research to Intervention
Authors: Koleilat Maria , Kim Loan Pham , Whaley Shannon E.
Published: June 2021

The goal of this study is to develop, pilot and evaluate a generalizable and sustainable intervention to prevent excessive gestational weight gain (GWG) among WIC participants in Southern California. Studies have shown that maternal obesity and excessive GWG lead to adverse health outcomes for the mother and her offspring, and intervention during pregnancy leads to improved outcomes. However, knowledge of the best way to intervene is still lacking. Qualitative data collection with WIC participants and staff will be used to develop an individual education program that addresses proper diet and exercise during pregnancy and includes monthly weight gain guidance and monitoring by a nutritionist using a visual GWG tracker. This prospective cohort study compares two groups of pregnant WIC participants. The intervention group will receive the individual education program and the control group will be a matched group of women from the same WIC site who gave birth in the months before the start of the intervention, therefore did not receive the intervention. Results of this study are expected to document the impact of the individual education on GWG and postpartum weight retention within the WIC setting. Should this intervention be successful, the materials and protocols can be distributed to other WIC programs in the nation. This research is supported by UCLA Subaward No. 1920 G QA126.
Maternal Genetic Risk Factors for Infant Zinc Deficiency
Authors: Friel James , Juan Sandra Castilo San , Qasem Wafaa , Leon Alejandra Serrano , Yurkova Natasha , Eck Peter
Published: June 2021

Zinc is an essential constituent of catalytic sites of multiple enzymes. Since all of these enzymes are involved in cellular functions, zinc deficiency will have adverse effects on reproduction, normal growth and development. Zinc deficiency was reported in healthy term infants and attributed to a decrease in zinc secretion in maternal breast milk (BM). Two single nucleotide polymorphisms (SNPs) in the membrane transporter SLC30A2 (ZnT2) cause decreased zinc secretion into BM. Through bioinformatics analysis we identified 14 additional SNPs causing amino acid changes. We aim to identify the functional changes caused by these 14 SNPs, with the initial objective to identify possible cellular mislocalization. We subcloned the SLC30A2 open reading frames into the Gateway entry plasmid pDONR221 and introduced the 14 SNPs using site directed mutagenesis. During transfer into expression plasmid we tagged SLC30A2 with red and green fluorescent proteins (mCherry, tGFP). We transfected individual plasmids into mammary epithelial cells and observed cellular targeting using epifluorescent imaging. The most common variants locate to secreting endosomes in mammary epithelial cells. Incorrect targeting of SLC30A2 eliminates its role in zinc secretion, resulting in zinc depleted BM. Mothers carrying risk genotypes for infant zinc deficiency can be identified. Funded by CRC and CIHR
The cellular hierarchy and composition of human breastmilk
Authors: Hassiotou Foteini , Hartmann Peter E.
Published: June 2021

During pregnancy and lactation, mammary stem cells remodel the breast into a milk‐secretory organ by proliferating and subsequently differentiating into both myoepithelial cells and lactocytes. Thus, we reasoned that the lactating gland, which is the fully mature organ, can offer a more comprehensive view of the mammary cellular hierarchy and dynamics than the resting gland. To non‐invasively access cells from the human lactating breast, we used freshly expressed breastmilk from which cells were isolated and characterized ex vivo for expression of markers of various lineages and differentiation stages. These included markers of pluripotent and multipotent stem cells, epithelial and mammary‐specific markers, hematopoietic and mesenchymal markers. Rare specimens of human lactating breast tissues were used to examine the origin of the different cell types identified in breastmilk. The ex vivo and in situ analyses were coupled by in vitro studies, which showed that along with the more differentiated cells, breastmilk contains progenitor cells and stem cells, some of which display pluripotency. These findings reveal a novel cellular hierarchy in breastmilk, characteristic of the lactating breast. Importantly, the presence of stem cells in breastmilk raises the question of the role of these cells for the breastfed infant.

Grant Funding Source: Women and Infants Research Foundation; Medela AG
Hypoxia Alters Iron Metabolism in Mouse Normal and Carcinoma Kidney Cells
Authors: Glenn Omolara‐Chinue , Bost Darrian , Ongeri Elimelda , Han Jian
Published: June 2021

Iron is required for oxygen delivery and energy production in cells. In hypoxia, there is diminished oxygen delivery to cells and this alters cellular iron metabolism. Response to hypoxia is cell‐ and tissue‐specific. This study investigated the effects of hypoxia on expression of iron‐related proteins in normal kidney cells (TCMK‐ 1) and kidney carcinoma cells (RAG). The TCMK‐1 and RAG cells were cultured to 70% confluence then exposed to 125 μM cobalt chloride for 0, 0.5, 1, 2, and 3 hours to induce hypoxia. Proteins were extracted and fractionated into cytosolic‐, membrane‐, and nuclear‐enriched fractions. Levels of iron‐related proteins, ferroportin (Fpn), ferritin H subunit (FtH), and transferrin receptor 1 (TfR1), were quantified by Western blot analysis coupled with optic densitometry. For both cell lines, hypoxia caused a time‐dependent increase in the levels of Fpn and TfR1. In contrast, levels of FtH decreased in both cell lines. Hypoxia resulted in nuclear stabilization of the hypoxia inducible factor, HIF‐1α, in both cell lines. These data indicate that hypoxia reduces cellular iron storage in normal and carcinoma kidney cell lines to maximize iron availability for metabolic utilization.
Tissue and Gender‐Specific Differences in the Iron Contents of Diabetic Mice
Authors: Harrison Krystal , Bost Darrian , Ongeri Elimelda , Fordahl Steven , Erikson Keith M , Han Jian
Published: June 2021

Iron is essential for life. The increase of total body iron stores has been associated with an increased risk for development of type 2 diabetes. Meprins are metalloproteases that are abundantly expressed in the brush border membranes of proximal kidney tubules and have been implicated in diabetic nephropathy. The objective of this study was to investigate the iron status in type I diabetic mice, and determine if meprin α deficiency impacts iron distribution. Two strains of mice, C57BL/6, which express normal levels of meprin α and meprin β (n=10 female, n=9 male), and C3H/He, which are deficient in meprin α (n=3 male, n=3 female) were studied. Low dose streptozotocin (STZ) was used to induce type 1 diabetes in 8 week old mice. Mice were sacrificed at week 11 post‐STZ injection and tissues (liver, spleen, brain, heart, and kidney) were harvested for iron analysis by Atomic Absorption Spectroscopy. Results showed tissue‐ and gender‐specific differences in iron levels in diabetic and non‐diabetic control mice. In both C57BL/6 and C3H/HE mice, male mice had over 10 times more iron compared to female mice in all tissues examined. Compared to non‐diabetic control mice, diabetic mice showed higher iron content in the heart, but lower in the liver. There was no difference in iron content between C57BL/6 and C3H/HE mice, which indicated that the level of meprin α did not affect iron status.

Grant Funding Source: none
Tocopherol levels response to n‐3 PUFA ingestion in women with and without Polycystic Ovarian Syndrome
Authors: Redinger Derek R , Retta Jemilla , Broughton K Shane
Published: June 2021

Polycystic ovarian syndrome (PCOS) is an endocrine disorder causing hyperandrogenism leading to hirsutism and chronic anovulation. Women with PCOS are much more likely to develop type‐2 diabetes with insulin insensitivity. Vitamin E (VE) levels were monitored in these women while consuming 2.3 g supplemental n‐3 PUFA for five months with additional vitamin D3 for the final two months. Twelve women with PCOS and 9 women without completed the study. Blood was taken monthly and serum α‐VE was assessed. Baseline VE was threefold higher in women with PCOS as those without PCOS. N‐3 PUFA ingestion immediately reduced plasma VE to 25% and 50% of baseline in polycystic and non‐polycystic women respectively. Women without PCOS had a smaller magnitude of absolute drop in VE attributable to lower initial levels and a better response. Polycystic women rebounded to baseline VE levels with two months of D3 supplementation while non‐PCOS women had a smaller rebound remaining at 75% of baseline VE levels. VE levels were less stable in the polycystic women than their non‐polycystic counterparts. This gives the impression that the polycystic women react less favorably to oxidative stress. The apparent VE response to elevated n‐3 PUFA ingestion will require further investigation but implies that VE supplementation may be necessary to maintain plasma levels when the long‐chain n‐3 PUFAs are ingested in Polycystic women.
Vitamin E TPGS Emulsified Zein Nanoparticles Enhanced the Uptake and Transport of Daidzin on Human Intestinal Epithelial Caco‐2 Cells
Authors: Zou Tao , Gu Liwei
Published: June 2021

Objective

Vitamin E TPGS 1000 emulsified zein nanoparticles (TZN) were designed to improve the absorption of daidzin, an isoflavone glycoside.

Methods

Zein nanoparticles (ZN) and TZN were fabricated using an anti‐solvent method. The morphology of ZN and TZN was characterized by Scanning Electron Microscope. Particle size was measured using dynamic light scattering. Release of daidzin loaded nanoparticles was determined on HPLC in simulated digestive fluids and pH 7.4 buffer. Cellular uptake of fluorescent nanoparticles was quantified and visualized using Fluorescence Microplate Reader and confocal laser scanning microscopy. Cellular transport of daidzin loaded TZN was investigated using human intestinal epithelial Caco‐2 cells in transwell plates.

Results

ZN and TZN were found spherical in shape with a mean size of around 200 nm and a low polydispersity. Daidzin loaded TZN had a slower daidzin release compared with daidzin loaded ZN in both simulated digestive fluids and pH 7.4 buffer. Confocal microscopy and cellular uptake studies suggested that the fluorescent TZN achieved significantly higher cellular uptake efficiency than the fluorescent ZN. Cellular transport study revealed that daidzin loaded TZN were transported more efficiently through Caco‐2 monolayer than daidzin solution.

Conclusion

These results suggested that TZN improved uptake and transport of daidzin on Caco‐2 cells.
Viscous dietary fibers added to a high fat diet decrease fatty liver, reduce hepatic gene expression of gluconeogenic enzymes and improve metabolic flexibility in obese rats
Authors: Brockman David A. , Chen Xiaoli , Gallaher Daniel D.
Published: June 2021

We have previously shown that increasing intestinal contents viscosity with viscous fiber reduces adiposity and improves glucose control in rats fed a high‐fat diet. In this study, we determined the effect of viscous fibers on the development of fatty liver and fuel flexibility in a model of diet‐induced obesity. Rats were fed a high fat diet (60% energy from fat) containing 5% fiber as cellulose (non‐viscous) or one of two highly viscous fibers ‐ hydroxypropyl methylcellulose (HPMC) or guar gum. After 10 weeks of feeding, HPMC and guar groups had lower liver weight, liver lipid and liver cholesterol compared to the cellulose group as well as decreased liver gene expression of the gluconeogenic enzymes G6Pase and PEPCK, indicating decreased fatty liver and reduced gluconeogenesis. Plasma adiponectin, an adipokine that correlates with hepatic insulin sensitivity, was also increased in the HPMC group. RQ was greater during the transition from fasting to fed state in the HPMC (p=0.055) and guar groups, suggesting a quicker shift from fatty acid to carbohydrate oxidation, or greater metabolic flexibility, possibly through improved glucose control. The HPMC group had greater in‐vitro palmitate oxidation in the muscle compared to the cellulose group, implying greater mitochondrial function. Consumption of viscous fibers with a high fat diet can reduce fatty liver and improve metabolic flexibility. Funded by MN Obesity Ctr
Hydroxytyrosol prevents hepatic endoplasmic reticulum stress in physiological concentrations
Authors: Giordano Elena , Davalos Alberto , Nicod Nathalie , Visioli Francesco
Published: June 2021

Olive oil is the essential component of the Mediterranean diet, which is associated with a lower incidence of chronic diseases and higher life expectancy. Hydroxytyrosol (HT) is a phenolic compound peculiar to olives and, hence, to virgin olive oil. Among the numerous health‐promoting properties of HT, recent findings demonstrated its ability to prevent LDL oxidation which may, ultimately, decrease cardiovascular risk. One rising risk factor for cardiovascular disease is endoplasmic reticulum (ER) stress. The roles played by the ER in cardiometabolism are likely to be relevant and manifold; mounting evidence indicates the ER as an important target of dietary or pharmacological intervention. We report the preventive activities of HT physiological concentrations toward ER stress in hepatocytes, as shown by real time‐RT PCR and Western Blot analysis of CHOP and BiP, two main components of the unfolded protein response (UPR), which is activated upon the accumulation of misfolded proteins in the ER. The protective activities of HT were superior to those of two isoflavones mostly found in soy, i.e. genistein and daidzein and of two thiolic antioxidants, i.e. lipoic acid and glutathione. Although in vivo confirmation is required, these data add mechanistic insights on specific olive phenols, such as HT, as cardioprotective compounds.

Research support: Ministerio C+I España/Marie Curie Amarout EU Programme
Depolymerization Optimization of Cranberry Procyanidins and Transport of Resultant Oligomers on Monolayers of Human Intestinal Epithelial Caco‐2 cells
Authors: Keqin OU , Liwei GU
Published: June 2021

Procyanidins in cranberries are predominantly polymers (>;85%). The objective of this study was to optimize the depolymerization of polymers and to investigate the absorption of resultant oligomers on Caco‐2 cell monolayers. Depolymerization conditions with or without added epicatechin were optimized using a response surface methodology. Depolymerization without added epicatechin yielded 202 μg oligomers (monomer through tetramers) per mg partially purified polymers (PP). Depolymerization with added epicatechin resulted in a higher yield of 644 μg oligomers per mg PP. Procyanidin oligomers yielded from both methods transported through Caco‐2 cell monolayer with transport ratios less than 2%. These results suggested that these newly generated oligomers are bioavailable albeit the aborption rates were low. With the aid of response surface methodology, the optimum depolymerization conditions were determined to be 60°C, 0.1 M HCl in methanol and 3 h without added epicatechin. The calculated maximum theoretical yield was 364 μg oligomers per mg PP. The optimum depolymerization condition with added epicatechin shared the same temperature, acid concentration and reaction time in addition to an epicatechin/PP mass ratio of 2.19. Its theoretical maximum oligomer yield was 1089 μg/mg. These conditions were verified by experimental data. Therefore, procyanidins depolymerization produced bioavailable oligomers on Caco‐2 monolayers with a good yield.
Synergistic Effects of Leucine and its Metabolites with Polyphenols on Irisin in Myotubes and Diet‐induced Obese Mice
Authors: Baggett Brooke , Bruckbauer Antje , Zemel Michael
Published: June 2021

FNDC5 is a muscle membrane protein stimulated by PGC1‐α; when cleaved, it releases irisin, which stimulates UCP1 expression and browning of white adipose tissue. We recently found leucine (0.5 mM) and its metabolite, HMB (5 μM), to synergize with low‐dose polyphenols to activate sirtuin signaling, resulting in significant increases in fatty acid oxidation (FAO) in adipocytes and myotubes. Here we report that treating adipocytes with conditioned media from myotubes treated with these combinations also results in increased FAO by 100–150% (p<0.05) via irisin. Resveratrol (200 nM)/leucine, resveratrol/HMB, cinnamic acid (1 μM)/HMB, chlorogenic acid (500 nM)/leucine, and chlorogenic acid/HMB stimulated significant increases in FNDC5 in myotubes (p<0.005), while the individual treatments exerted no effect. Irisin secretion was increased in response to resveratrol‐leucine (234%, p=0.008), resveratrol‐HMB (122.5%, p=0.00001), and cinnamic acid‐leucine (40%, p=0.0005) combinations. Supplementing diet‐induced obese mice with low‐dose resveratrol (12.5 mg/kg diet) and leucine (24 g/kg diet) for 6 weeks resulted in an 86% increase in plasma irisin (p=0.03), a two‐fold increase in PGC1‐α in white adipose tissue (p=0.04) and a 344% increase in UCP1 expression (p<0.05). These data demonstrate that leucine‐polyphenol combinations stimulate irisin release and browning of adipose tissue.