bluuebunny/crossref_metadata_2025_split huggingface dataset:
Citrobacter rodentium Infection Alters Murine Colonic microRNA Signature
Authors: Wen Bijun , Chen Jianmin , Taibi Amel , Comelli Elena 
Published: June 2021

MicroRNAs (miRs) have been suggested to play a part in the interaction between pathogenic bacteria and host cells. Citrobacter rodentium is a murine pathogen causing transmissible colonic hyperplasia and colitis with similar pathogenicity as the foodborne enterohaemorrhagic Escherichia coli O157:H7 in humans. This study aimed to examine if colonic microRNA signature is altered during C. rodentium infection. C57Bl6/J male mice were randomized to C. rodentium‐infected or control group, and sacrificed at the peak of infection (10 days post‐infection). Crypt hyperplasia and intestinal inflammation were confirmed by histology and in vivo permeability test. Colonic RNA was used to profile 578 miRs by NanoString technology. Statistics and hierarchical clustering were performed in R. Gene targets of the differentially expressed miRs were identified in silico by prediction algorithms and cross‐matching with experimentally verified targets databases. Ninety‐four miRs were differentially expressed (p<0.05), with 42 downregulated and 52 upregulated vs control (0.2‐8.6 fold), and infected samples clustered together and separately from the controls based on their expression profile. Many of these miRs, including miR‐21, miR‐148a, and miR‐152, are known to regulate barrier function, cell proliferation and inflammatory pathways. Moreover, prediction analysis revealed that globally gene targets are mainly involved in cell cycle and immune response. This study shows that C. rodentium infection alters the colonic microRNA signature; differentially expressed miRs may be involved in the pathogenicity mechanism and serve as targets of nutritional or therapeutic interventions.Funding: NSERC, JP Bickell Foundation, and NSERC Alexander Graham Bell Canada Graduate Scholarship
Quantity and Variety in Fruit and Vegetable Intake and Cardiovascular Disease (CVD) Risk: The Women's Health Initiative (WHI)
Authors: Bhupathiraju Shilpa , Tinker Lesley , Dubowitz Tamara , Johnson Karen , Seguin Rebecca , Manson JoAnn , Hu Frank 
Published: June 2021

Epidemiological data have shown a protective effect of fruit and vegetable (FV) intake on CVD. Consequently, dietary guidelines recommend increasing FV intake and, most recently, have also suggested increasing variety. We examined the independent roles of quantity and variety in FV in relation to incident CVD among 88,249 women in the WHI. Diet was assessed at baseline using a validated FFQ. Variety was defined as the number of FV consumed in the past 3 months. Potatoes, starchy vegetables, and fruit juice were not included. During 18 years of follow‐up, we documented 5672 incident CVD cases. In multivariable analyses, after adjusting for dietary and non dietary covariates, those with the highest FV intake (median=3.9 servings/d) had a 12% lower CVD risk (95% CI 4%‐20%) compared to those with the least intake (median =1 serving/d). Higher fruit intake was associated with 34% (95% CI 19%‐48%) lower coronary heart disease risk while higher vegetable intake was associated with a 15% (95% CI 3%‐25%) lower stroke risk. Conversely, quantity‐adjusted variety was not associated with CVD (HR=0.97, 95% CI 0.86‐1.10). Our data suggest that quantity, rather than variety, in FV intake is associated with lower CVD risk. Policy efforts should continue to focus on increasing overall FV intake in the population.Supported by NIH, NHLBI, HHS grants/contracts HL60712, K01HL10880705, HHSN268201100‐046C/‐001C/‐002C/‐003C/‐004C and AHA grant 13POST14370012.
ATP7a Silencing Impairs Iron Transport in Fully‐Differentiated Rat Intestinal Epithelial (IEC‐6) Cells
Authors: Ha Jung‐Heun , Gulec Sukru , Doguer Caglar , Flores Shireen , Han Yi , Wang Xiaoyu , Collins James 
Published: June 2021

Intestinal iron absorption is tightly regulated since no active excretory pathways for iron exist in mammals. Iron homeostasis isintertwined withthat of copper (Cu), but specific molecular interactions are yet to be defined. To further evaluate iron‐copper interplay in the mammalian intestine, low, control, or high‐iron diets (3, 50and 10,000 ppm, respectively) were fed to weanling rats ad libitum for 5 weeks. Rats fed the low‐iron diet developed iron‐deficiency anemia, and genes involved in duodenal Fe homeostasis increased significantly as compared to the other groups. Interestingly, genes encoding proteins involved in Cu homeostasis were also upregulated in the low Fe group, including copper‐transporting ATPase 1 (ATP7a) and metallothionein

Low iron
Control iron
High iron

Hemoglobin
2.8 (0.29)****
13.09 (0.64)
13.14 (0.64)

Hematocrit (%)
14.05 (2.58)****
50.61 (4.78)
50.47 (1.15)

Atp7a mRNA
6.34 (2.69)****
1.03 (0.28)
2.18 (1.31)

Metallothionein 1a
12.59 (15.81)*
1.85 (2.40)
1.30 (0.94)

Dmt1 mRNA
179.89 (84.5)****
1.07 (0.42)
1.67 (0.88)

Dcytb mRNA
6939.76 (4386.76)****
1.70 (1.88)
17.56 (21.17)

Ferroportin1 mRNA
3.95 (1.55)****
1.15 (0.62)
1.66 (1.13)

Transferrin receptor 1 mRNA
10.67 (2.83)****
1.09 (0.47)
0.71 (0.25)

We thus hypothesized that ATP7a function is important for intestinal iron metabolism. To test this postulate, we blocked ATP7a expression in rat IEC‐6 cells by shRNA‐mediated gene silencing. Notably, ATP7a knock down (KD) impaired Fe uptake and efflux in fully‐differentiated cells. Moreover, ATP7a KD decreased doudenal cytochrome b and ferroportin 1 mRNA expression, while conversely, hephaestin (Heph) gene expression increased significantlyimageConsistent with Heph induction, ferroxidase (FOX) activity in total cell lysates increased in the KD cellsimageThese observations demonstrate that ATP7a activity is necessary for iron absorption in IEC‐6 cells. Altered expression of iron transport‐related genes in the KD cells could be the underlying molecular mechanism by which ATP7A alters iron flux. Furthermore, increased Heph expression and FOX activity may be a compensatory response to increase iron transport.
TNFα Post‐Translationally Targets ZnT2 to Lysosomes to Activate Lysosomal‐Mediated Cell Death and Mammary Gland Involution
Authors: Hennigar Stephen , Kelleher Shannon 
Published: June 2021

Mammary epithelial cells undergo widespread lysosomal‐mediated cell death (LCD) during early mammary gland involution. Recently, we demonstrated that TNFα, a cytokine released during early involution, redistributes the zinc (Zn) transporter ZnT2 to accumulate Zn in lysosomes and activate LCD and involution. The current objective was to determine how TNFα retargets ZnT2 to lysosomes. We hypothesized that TNFα signaling dephosphorylates ZnT2 to uncover a highly conserved dileucine motif (L294L) in its C‐terminus, allowing adaptor protein complex‐3 (AP‐3) to bind and traffic ZnT2 to lysosomes. Confocal micrographs showed that TNFα redistributed wildtype (wt) ZnT2 from late endosomes (Pearson's coefficient=0.202±0.05 and 0.097±0.03; P<0.05) to lysosomes (0.292±0.03 and 0.649±0.03; P<0.0001), which increased lysosomal Zn (P<0.0001) and activated LCD (P<0.0001) compared to untreated cells. Mutation of the dileucine motif (L294V) eliminated the ability of TNFα to redistribute ZnT2 from late endosomes to lysosomes, increase lysosomal Zn, or activate LCD. Moreover, TNFα increased (P<0.05) AP‐3 binding to wt‐ZnT2 but not to L294V. Finally, using phospho‐ and dephospho‐mimetics of predicted phosphorylation sites (T281, T288, and S296), we found that dephosphorylated S296 was required to target ZnT2 to accumulate Zn in lysosomes and activate LCD. Our findings suggest that women with variation in ZnT2′s C‐terminus may be at risk for inadequate involution and breast disease due to the inability to target ZnT2 to lysosomes.Supported in part by R01HD058614.
High‐Protein Diet during Gestation Promotes Adiposity and Food Intake in Female Rat Pups in the Longer Term
Authors: Desclée de Maredsous Caroline , Oosting Annemarie , Delteil Corine , Blachier François , Barbillon Pierre , Mary‐Huard Tristan , Tomé Daniel , Oozeer Raish , Davila Anne‐Marie 
Published: June 2021

Dietary proteins during perinatal period are an important nutritional factor for later life metabolic health and disease risk (Michaelsen et al, 2012). The aim of this study is to determine the effect of maternal high‐protein (HP) diet during gestation or lactation on offspring metabolic response to a western diet challenge after weaning. Three groups of Wistar rat dams received either control diet (20% proteins) during gestation and lactation (C group), HP diet (55% proteins) during gestation (HPgest group), or HP diet during lactation (HPlact group). From weaning until the age of 10 weeks, female pups were fed either control or western (W) diet.When compared to C and HPlact pups, HPgest pups have less visceral adipose tissue (AT) at weaning (p=0.02) but have at 10 weeks‐old a higher free fatty acids plasma concentration (p=0.04), more subcutaneous AT (p=0.02) and more adipocytes (p=0.007).In addition, when compared to C pups and to HPlact pups, HPgest pups fed W diet have a higher weight gain (gestation diet*diet after weaning*time effect: p<0.0001), an increased food intake (gestation diet*diet after weaning effect: p=0.01) and a higher adiposity at 10 weeks (gestation diet*diet after weaning effect: p=0.006 in absolute weight and p=0.02 in % body weight).These results show that maternal HP diet during gestation, but not lactation, leads to a higher sensitivity of female pups to obesity. The programming effect induced by HP diet during gestation promotes an enhanced differentiation and/or proliferation of adipocytes, thus increases the capacity of pups to store fat.
The acute effects of protein quantity and distribution on appetite control, satiety, and food intake in overweight young women
Authors: Leidy Heather , Roenfeldt Connor , Alwattar Ammar , Shafer Rebecca 
Published: June 2021

PurposeTo examine the acute effects of protein quantity and protein distribution on appetite control, satiety, and daily food intake in overweight young women who habitually eat breakfast.Design20 young women (age: 19±1y; BMI: 28.9±0.6kg/m2) completed 4 meal patterns in which the protein content of the breakfast and lunch meals varied.

Normal Protein Breakfast +Normal Protein Lunch(NPB‐NPL)
High Protein Breakfast + High Protein Lunch (HPB‐NPL)
Moderate Protein Breakfast + Moderate Protein Lunch (MPB‐MPL)
High Protein Breakfast + High Protein Lunch (HPB‐HPL)

Protein at Breakfast (g)
10
30
20
30

Protein at Lunch (g)
15
15
25
30

Sum of Protein at Breakfast and Lunch (g)
25
45
45
60

The women followed each pattern for 3 acclimation days. On the 4th day of each pattern, the respective 10‐h testing day was completed. Blood samples and assessments of perceived appetite and satiety were assessed at specific times throughout the day. Prior to dinner, a brain scan was completed using fMRI to identify brain activation in response to food stimuli. Ad libitum dinner and evening snacks were also provided.ResultsOnly the HPB‐HPL pattern led to daily reductions in hunger, desire to eat, and prospective food consumption as well as daily increases in PYY concentrations vs. NPB‐NPL (all, P<0.05), whereas the HPB‐NPL and MPB‐MPL did not. In addition, the HPB‐HPL and MPB‐MPL patterns led to blunted pre‐dinner cortico‐limbic neural activation vs. NPB‐NPL (both, p<0.01). No other differences in appetite control and satiety were detected between patterns. Lastly, no differences in evening snack behavior or daily food intake were detected between patterns.ConclusionsAlthough a high protein breakfast in combination with a high protein lunch led to improved appetite control and satiety, these responses did not translate into reductions in evening snacking or daily intake in women who habitually consume breakfast. Further, no protein‐related dose‐responses or protein distribution effects were detected.Funding Egg Nutrition Center & The Beef Checkoff
Protecting a woman's right to breastfeed: the extension of maternity leave in Vietnam
Authors: Hajeebhoy Nemat , Nguyen Tuan , Nguyen Phuong , Mannava Priya , Phan Linh , Vu Ha , Mathisen Roger , Do Phuong 
Published: June 2021

Exclusive breastfeeding in the first six mo of life is critical to child development and health. Effective from May 1, 2013, Vietnam became one of the first lower‐ to middle‐income countries to offer 6‐month paid maternity leave (6mo‐PML). We analyzed data from different sources to 1) describe the process of adopting the 6mo‐PML policy, 2) examine perceptions of employed women about this policy, and 3) assess the association between maternity leave and the exclusive breastfeeding practice. Five key components leading to policy change were the establishment of partnerships, consensus building among various stakeholders, evidence‐based policy advocacy, development of messages and materials, and engaging the media. An online survey (n = 1,005) showed employed women believed that 6mo‐PML was beneficial for infant's health (72%), mother's health (59%), society (45%) and family (34%). To avail of 6mo‐PML, mothers needed support from employers to maintain positions (80%) and hire temporary staff (48%). Findings from an onsite survey (n = 6,240) show that the percent of mothers who returned to work when the infant was < 4 mo, 4 mo and 5 mo were 5%, 15% and 22%, respectively. Mothers who returned to work had a statistically lower prevalence of exclusive breastfeeding than those who did not in the overall sample (20% vs. 34%) and for all age groups (< 4 mo: 35% vs. 42%; 4 mo: 19% vs. 26%; and 5 mo: 9% vs. 15%). Adjusted OR for returning to work was 0.65 (95%CI 0.53, 0.80). With increasing numbers of women entering the labor force, adoption of maternity protection policies is critical to enabling working mothers to optimally breastfeed their children.Funding: Bill & Melinda Gates Foundation, through Alive & Thrive, managed by FHI 360
EFFECT OF LOW GLYCEMIC INDEX DIET ON APOLIPOPROTEIN B AND LDL PARTICLE SIZE
Authors: Srichaikul Korbua , Ireland Chris , Kendall Cyril , Sievenpiper John , Lamarche Benoit , Jenkins David 
Published: June 2021

BackgroundApolipoprotein B (Apo B) and small LDL particles have been strongly associated with increased coronary artery disease while low glycemic index diets (GI) may reduce risk. We have therefore assessed the effect of consumption of a low GI diet on Apo B and LDL particle size.Methods155 type 2 diabetic subjects treated with antihyperglycemic agents were randomized and completed either 6 months of high fiber or low glycemic index dietary advice in a parallel design. Serum samples were obtained pre‐treatment and at the end of the 6 month study period.ResultsThere was no significant treatment difference in Apo B but a significant reduction in estimated small dense LDL cholesterol (sdLDL‐C) on the low GI diet by ‐0.15 ± 0.08 mmol/L compared to the high fiber diet (p=0.048). No significant treatment differences were seen in LDL particle size distribution. Dietary glycemic load, not glycemic index, correlated positively to serum levels of sdLDL‐c (Rho=0.17, p=0.036), while correlated negatively with serum levels of medium LDL particles (Rho=‐0.17, p=0.042) and large LDL particles (Rho=‐0.18, p=0.026).ConclusionThese findings suggest a benefit of low glycemic index diets in reduction of sdLDL‐c levels in type 2 diabetes.Funding Canadian Institutes of Health Research, Canada Research Chair Endowment of the Federal Government of Canada, and Barilla (Italy).
Proteomic analysis of plasma in adult active pulmonary tuberculosis patients with diabetes mellitus
Authors: Zhang Xiulian , Ma Aiguo , Sun Shuangling , Sun Yongye 
Published: June 2021

Abstract:There is a high burden of both diabetes and tuberculosis in China. Althoug both diabetes and tuberculosis have been the objects of intensive study the association between the two diseases is not fully understood. The aim of this study was to determine whether thetqualitative and quantitative differences in expression of some protein expression in plasma could be related to active pulmonary tuberculosis complicated with diabetes. Using two‐dimensional gel electrophoresis and mass spectrometry we analyzed expression of the proteins associated with active pulmonary tuberculosis complicated with diabetes. Results showed that under the baseline condition, the levels of a‐1 antitrypsin precursor, vitamin D‐binding protein precursor, CD5 antigen like precursor, clusterin precursor, apolipoprotein A‐I precursor, haptoglobin and fibrinogen g‐chain differed between patients with active pulmonary tuberculosis and active pulmonary tuberculosis complicated with diabetes. Western blott results confirmed differential expression of clusterin. These results suggest that active pulmonary tuberculosis complicated with diabetes may be associated with specific protein expression pattern in plasma. C‐terminal haptoglobin is a possible candidate protein of interest, which might be a link between active pulmonary tuberculosis and diabetes. The dynamics of protein expression during disease progression may improve our understanding of the pathogenesis of active pulmonary tuberculosis complicated with diabetes.Supported by NSFC‐81172662
Regulatory Role of Endothelial CD47 during Leukocyte Transmigration
Authors: Leick Marion , Azcutia Veronica , Newton Gail , Luscinskas Francis 
Published: June 2021

The vascular endothelium plays a critical role in inflammation and leukocyte recruitment by expression of adhesion molecules and leukocyte chemoattractants. Adhesion molecules bind leukocytes and transmit signals to the endothelial cells (EC) required for transendothelial migration (TEM). An important unanswered question is how ECs integrate the signals arising from leukocyte engagement of multiple adhesion molecules. CD47, also known as Integrin Associated Protein, is a broadly expressed glycoprotein and binds thrombospondin‐1 and leukocyte expressed Signal Regulatory Proteins (SIRPα and SIRPg). Besides these “in trans” interactions, CD47 also interacts “in cis” (in the same plasma membrane) with multiple integrins. We previously reported that endothelial CD47 plays a role in TEM and transmits intracellular signals upon engagement. Interestingly, CD47 signals phenocopy those occurring after engagement of ICAM‐1. We hypothesized CD47 interacts with ICAM‐1 to form a protein complex in EC plasma membrane and that this complex binds leukocytes and transmits intracellular signals during leukocyte TEM. Here we report CD47 associates with ICAM‐1 in EC by Fluorescence Lifetime Imaging Microscopy of Förster Resonance Energy Transfer (FLIM‐FRET). Furthermore, ICAM‐1 crosslinking‐induced signaling through pyk2 and src kinases was impaired in CD47‐/‐ mouse heart ECs (MHEC) as compared to WT MHEC. This was also demonstrated in HUVEC silenced for CD47. Understanding how CD47 interacts with different molecules will clarify its role in leukocyte recruitment and EC dependent mechanisms that regulate TEM.Supported by grants from National Research Fund of Luxembourg (FNR, Award # 4800397) and NIH HL‐36028.
Measuring Child Length and Height: Assessing the Accuracy of a Portable Infrared‐based Digital Tool
Authors: Baxter Jo‐Anna , Roth Daniel , Zlotkin Stanley , Yin Shi , Milgram Paul , Mouzaki Marialena 
Published: June 2021

Accurate measurement of growth in infants and children is important, as it reflects a child's nutritional status and overall health. Conventional methods of measuring length and height are challenging due to limited access to appropriate tools, poor tool quality, and lack of child cooperation. Pediatric Platform for Anthropometry (PePA) is a portable, computer‐assisted infrared‐based tool that measures length/height without direct child contact. This study investigated PePA's accuracy by comparing length/height measures to the gold standard (length board or stadiometer). The precision and acceptability of PePA and the gold standard were also assessed. In a preliminary analysis of 316 eligible children (0‐18 years), 278 participants' PePA and gold standard measures met the study criteria for inclusion in the analysis. For 6% of those eligible, no successful PePA measures were obtained. The overall intraclass correlation (ICC) [95% CI] between PePA and the gold standard was 0.9988 [0.9985, 0.9991]. The ICC for length only (n=16) and height only (n=262) was 0.9840 [0.9286, 0.9951] and 0.9981 [0.9976, 0.9985], respectively. The mean (±SD) time to obtain a PePA measure was less than the standard tool (8.4±3.2 versus 14.1±5.3 seconds, respectively; p<0.05). Preliminary results suggest that PePA has a very high concordance with the gold standard and is faster in obtaining a measure.Research support was provided by a Hospital for Sick Children Innovation Grant.
Dietary Predictors of Growth in Vulnerable Young Children from Four Low‐Resource Countries: a Longitudinal Study
Authors: Lander R , Krebs N , Mazariegos M , Garces A , Westcott J , Goco N , Tshefu A , Pasha O , Chomba E , Hambidge M ,   First Bites Study Group
Published: June 2021

Longitudinal associations between dietary factors and growth patterns were examined in infants/toddlers from Zambia, DRC, Guatemala and Pakistan in a secondary analysis of a previously published large randomized efficacy trial of daily meat vs fortified cereal supplements as complementary foods. Growth (i.e. z‐scores for length (LAZ), weight (WLZ)), diet (i.e. infant/young child feeding practices (IYCFP), food groups consumed), and SES data were collected from 929 breastfed children aged 6‐18 mo (arms combined). Diet at 9 and 12 mo were correlated with growth measures at 12 and 18 mo, respectively, using adjusted IYCFP (terciles), multiple linear regression and logistic regression analyses. Significant findings (p<0.05) include: 1) no dietary meat/fish/insects (MFI) and no milk/dairy (MD) at 9 mo were associated with reduced LAZ at 12 mo; 2) increased risk (OR) of stunting (LAZ<‐2SD) at 12 mo was found in boys (1.9) and low SES (1.7) and associated with low dietary diversity (DD) (3.2), no MFI (1.9), and no MD (2.3) at 9 mo; 3) low DD and no MD at 12 mo were associated with decreased LAZ at 18 mo, while low food variety, low DD and no MFI with reduced WLZ; 4) increased risk of stunting at 18 mo was found in boys (1.8) and associated with no MD (1.7) at 12 mo. This longitudinal study emphasizes the critical role of the quality of complementary feeding on growth in the first 2 years of life in children from low‐resource settingsFunded by NIH/NICHD/ODSAcknowledgement: LL Wright, NICHD, Rockville, MD
Selective Carotenoid Growth Inhibition in Breast Cancer: Independence of Hormonal Sensitivity
Authors: Smith Joshua , Gong Xiaoming , Rubin Lewis 
Published: June 2021

BackgroundCarotenoid intake has been associated with ↓ed cancer risk, including breast cancer. We tested if specific carotenoids inhibit cancer cell proliferation or induce apoptosis and interaction with chemotherapeutic agents.MethodsHormone sensitive and triple negative breast cancer lines and immortalized breast cells were treated with carotenoids (β‐carotene, lycopene [LYC], lutein [LUT] or astaxanthin; 0.5‐2.0 µM) singly or in combination with taxanes. Cell proliferation was analyzed by MTT and EdU assays; intracellular ROS, cell cycle and apoptosis were assayed by flow cytometry. RT‐PCR arrays were used to evaluate gene expression ± carotenoid exposure. Carotenoid‐drug combinatorial effects were determined using the Chou‐Talalay method.ResultsLUT and LYC significantly ↓ed cancer cell proliferation (threshold, < 0.5µM) with little dose‐dependency; β‐carotene and astaxanthin had no significant effects. LUT‐, LYC‐mediated growth inhibition was similar to that induced by taxanes. LUT + taxane synergistically inhibited cancer cell proliferation. LUT also ↑ed intracellular ROS and G1 arrest and expression of apoptosis‐related genes.ConclusionLUT and LYC inhibit breast cancer cell growth independent of cell hormone receptor status and additively‐synergistically with taxanes. These carotenoid‐mediated effects appear to involve inducing cell cycle arrest and increasing apoptosis. LUT (best known for effects on eye and brain health) and LYC may be important adjuncts to breast cancer chemotherapy.