bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardio‐Pulmonary Coupling I: Ejection Fraction Effects on Initiator Signals of Next Breathing
Authors: Sun Xingguo
Published: June 2021

INTRODUCTION

Since 2011 APS, we introduced new theory of breathing control. The lung breath generated O2, CO2 and [H+] oscillations as trigger of next breath.

HYPOTHESIS

We assessed the hypothesis that reduced left ventricle ejection fraction (EF) decrease the amplitude of arterial O2, CO2 and [H+] oscillations, due to the mixed‐chamber function of LV for these oscillation information.

METHODS

We recorded PO2, PCO2 and flow at mouth using 50Hz database; then based on dead space volume and functional residual capacity to calculate alveolar partial pressure oscillations of O2 and CO2 (same as blood). EF was used to calculate the magnitudes of arterial PO2 and PCO2 oscillation.

RESULTS

Calculated magnitudes of oscillation PO2 and PCO2 in alveolar were ~7mmHg. While 5:1 for ratio of heart rate to breathe, using EF=75% calculated magnitudes were ~5mmHg in arterial blood. But using EF=20%, the magnitudes decreased to <2mmHg in arterial blood. The lower EF, the weaker signal (magnitude) at artery. This will results that mean of O2 and CO2 at central chemical sensors is unstable, and then breath control ¡°gain¡± goes up and down.

CONCLUSIONS

Breathing lung generated O2 and CO2 oscillations magnitude decreased in arterial blood are influenced by EF is a mechanism of Cardio‐Pulmonary Intra‐Coupling
Changes in innate immune pathway and proteins of Caenorhabditis elegans during Cronobacter sakazakii infection
Authors: BALAMURUGAN KRISHNASWAMY , Sivamaruthi BhagavathiSundaram
Published: June 2021

Caenorhabditis elegans is a potent model system for the study of host‐pathogen interactions. C. sakazakii is an opportunistic pathogen that infects and cause mortality in C. elegans. The role of host immune regulatory pathways and proteomic changes in host during C. sakazakii infection was analyzed. Feeding based assay, bacterial colonization, Chemotaxis assay and Pharyngeal pumping assay were performed using MAPK mutant C. elegans. Total protein extracted from the infected host was analyzed by SDS‐PAGE. C. sakazakii infected MAPK mutants (sek‐1 and pmk‐1) died with the LT50 of 120 ± 6 h and 96 ± 6 h, respectively. Lawn avoidance behavior was not observed in the mutant worms exposed to C. sakazakii. Bacterial accumulation and Pharyngeal pumping rate was measured. SDS‐PAGE studies revealed the variation in C. elegans total proteins after exposure with C. sakazakii. Comparative analysis of host proteins from previous reports revealed that C‐type lectin and UN coordinated family members were regulated during infection. [This work has been financially supported by CSIR, DST, ICMR and DBT, Government of India, New Delhi, India].
Decreased expression and phosphorylation of ROK1, ROK2, MLCpS19, MYPT1pT696/pT853, and CPI‐17pT38 in gastric antrum smooth muscles of Lep ob/ob mice
Authors: Perrino Brian A , Bhetwal Bhupal P , An Changlong
Published: June 2021

Diabetic gastroparesis is a common complication of Type 1 and Type 2 diabetes, adversely affecting the patient's quality of life with unpleasant symptoms of abdominal discomfort, nausea, and vomiting. Its associated morbidities are a costly health care burden. The Lepob/ob mouse model of obesity and diabetes develops delayed gastric emptying, suggesting that this model may be used to investigate if smooth muscle dysfunction contributes to the pathophysiology of diabetic gastroparesis. This study's objective is to determine if the antral dysmotility of diabetic gastroparesis might be due to differences in expression and phosphorylation of regulatory contractile proteins in gastric antrum smooth muscles from Lepob/ob mice. Gastric antrum smooth muscles obtained from male Lepob/ob and control C57BL6 mice at 7, 12, and 20 weeks of age showed significantly decreased expression and phosphorylation of ROK1, ROK2, MLCpS19, MYPT1pT696/pT853, and CPI‐17pT38 as measured by SDS‐PAGE, western blotting, and enhanced chemiluminescent immunodetection. Carbachol (Cch)‐evoked contractions of Lep ob/ob antrum smooth muscle strips were also significantly decreased. These findings suggest that inhibition of MLCP may be impaired in antrum smooth muscles from Lepob/ob mice, and contribute to the antral dysmotility of diabetic gastroparesis. This work was supported by NIH grant RR08751.
Contributors to iodine status among children in the U.S.
Authors: Perrine Cria G. , Sullivan Kevin M. , Flores-Ayala Rafael , Grummer-Strawn Laurence M.
Published: June 2021

While pregnant women and some subgroups of reproductive age women may be at risk for iodine deficiency, data also suggest that iodine intake among children may be above requirements in the U.S. Our objective was to describe the association of iodine sources with iodine status among children. We analyzed 2007–2008 National Health and Nutrition Examination Survey (NHANES) data from urinary iodine (UI) spot tests for children 6–12 y (n=1150), and used WHO criteria for iodine status (median UI 100–199 μg/L=adequate; 200–299 μg/L=above requirements; ≥300μg/L=excess). Overall median UI was above requirements for children 6–12 y (213 μg/L, 95% CI 197–238). Median UI increased by quartile of dairy intake and ranged from adequate in the lowest quartile (156 μg/L, 131–192 μg/L), to above adequate in the highest quartile (293 μg/L, 248–369 μg/L). Median UI was 303 μg/L (253–401 μg/L) among the 15% of children taking a dietary supplement that contained iodine, compared to 205 μg/L (192–221 μg/L) among those not taking a supplement. In regression analyses adjusted for sociodemographic and other dietary factors, recent dairy intake, recent supplement use, and regular table salt use were significantly positively associated with UI levels among children. Public health strategies to reconcile low iodine intakes among pregnant women and above adequate intakes among children will need to consider dairy products, dietary supplements, and salt as important sources of iodine among children.
ApolipoproteinA‐1 expression attenuates Cigarette Smoke or Elastase‐generated Emphysema in Mice
Authors: Park Sung-woo , Lee Eun hee , Lee Eun-ju , Kim Hee jeong , Jang An soo , Uh Soo-taek , Kim Yong hoon , Park Choon-sik
Published: June 2021

Rationales

Apolipoprotein A‐1 (ApoA1) have anti‐inflammatory and antioxidant properties as well as cholesterol efflux.

Objectives

To determine if the expression of human ApoA1 within the lung protect against the development of emphysema

Methods

Transgenic human ApoA1 mice(ApoA1 TG) were exposed to CS for 6 month and compared to control transgenic mice. Other ApoA1 TG mice were treated with intratracheal elastase in order to generate emphysema. Measurement; Lung inflammation, oxidative injury was measured in the lung. Emphysema was determined by measuring the mean linear intercept(Lm). Proinflammatory cytokines in the BALF were measured by ELISA and analysis of apoptosis using the TUNEL assay.

Results

Compared with control TG mice, ApoA1 TG mice had significantly less lung inflammation, oxidative damage and apoptosis as well as decreased levels of proinflammatory cytokines. ApoA1 attenuated the development of emphysema in both the smoke‐induced and elastase‐generated models.

Conclusions

Overexpression of ApoA1 prevents CS and elastase induced emphysema in mice. Augmentation of ApoA1 in the lung could be effective for the prevention or treatment of emphysema/COPD.
Fatty acid‐mediated endoplasmic reticulum stress in the liver in vivo: Differential response to saturated and unsaturated fatty acids
Authors: Nivala Angela , Reese Lauren , Hemenway Erica , Gentile Christopher , Pagliassotti Michael
Published: June 2021

In cell systems, saturated fatty acids are generally more cytotoxic than unsaturated fatty acids. In the present study we examined hepatic cytotoxicity in response to unsaturated and saturated fats in vivo. Lipid emulsions containing glycerol, phosphatidylcholine, penicillin (CON, n=6) and either soybean oil (UNSAT, n=7) or lard oil (SAT, n=7) were infused intravenously into rats over a 4 hour period under conditions in which glucose and insulin levels were held constant. Free fatty acids levels were 0.5 ± 0.1 mM (mean ± SD) in CON and were increased to 1.7 ± 0.3 mM and 1.6 ± 0.3 mM in UNSAT and SAT, respectively. Glucose and insulin levels were not different among groups. Markers of endoplasmic reticulum (ER) stress and activation of inflammatory pathway signaling were increased in livers from SAT and UNSAT compared to CON, but were increased to a greater extent in SAT compared to UNSAT. Several genes linked to inflammation were significantly increased in adipose tissue of UNSAT and SAT compared to CON, but were increased to a greater extent in SAT compared to UNSAT. These data suggest that elevated free fatty acids can induce hepatic ER stress in vivo. In addition, SAT fatty acids appear to be more cytotoxic than UNSAT fatty acids in vivo.
MicroRNAs to Pathways in Stem Cells and Cancer
Authors: Blelloch Robert , Subramanyam Deepa , Melton Collin , Judson Robert , Belair Cassandra
Published: June 2021

Using a combination of global microRNA knockouts together with re‐introduction of individual microRNAs, we have been dissecting microRNA‐regulated pathways in embryonic stem cells and cancer. I will describe our latest findings in how microRNAs regulate the differentiation and de‐differentiation of stem cells. I will also describe recent results on the role of miRNAs in tumor progression using a mouse model of prostate cancer.
Repeat RNAs in Chromosome Regulation and Mis‐Regulation in Cancer
Authors: Lawrence Jeanne Bentley , Hall Lisa L , Carone Dawn M
Published: June 2021

This talk will discuss recent findings supporting broad roles of repeat RNAs in chromosome structure and regulation. Earlier we demonstrated that RNA hybridization using the “Cot‐1” (repetitive) human genomic fraction as a probe provides a convenient assay for transcriptional silencing of a chromosome, evident as a region lacking in Cot‐1 RNA signal. While the copious Cot‐1 RNA signal is widely assumed to reflect repeats in introns of expressed genes, our findings indicate otherwise. In dissecting the components of Cot‐1 RNA, we unexpectedly found that particular human satellites are silent in normal cells but grossly over‐expressed nuclear repeat RNAs in cancer. Other findings implicate RNA from particular types of interspersed repeats in the regulation of euchromatic versus heterochromatic chromosomes. Broad implications for the role of “junk” DNA/RNA will be discussed.
Moving science from the laboratory to the field
Authors: James Anthony Amade
Published: June 2021

Novel technologies for public health applications are fostering analyses and inquiry of the roles of communities in research and what they can expect to receive in exchange for their participation. Community engagement activities addressing the results of these analyses are challenging for new scientific approaches, especially those based on controversial strategies and those in which some risks are poorly understood or determined. For many applications, no explicit body of community engagement knowledge exists from which researchers can derive guidance about approaches most likely to be effective in different contexts. Frameworks have been developed recently that provide starting points for broader discussions of community engagement in global health research, particularly as it relates to the development, evaluation, and application of new technologies. Experiences in a number of countries will be presented highlighting unique and common features, and lessons‐learned.
Assessing school personnel knowledge of wellness policies
Authors: McWhinney Sharon , McDonald Andrea , Dawkins-Moultin Lenna , Outley Corliss , McKyer Lisako
Published: June 2021

Wellness policies were formulated to assist school districts in promoting student health and wellness, prevent and reduce childhood obesity, and provide assurance that school nutrition guidelines meet the minimum federal standards. For policies to be effective school personnel must know what they are and how they can participate in the implementation. Structured interviews were conducted among 39 fourth grade teachers, principals, nurses and food service directors, to determine their knowledge of the wellness policies being implemented in the local schools. Responses were audio recorded, transcribed and analyzed using Atlas Ti. Two or more similar responses were determined to be a theme. Participants indicated that nutrition and wellness were promoted primarily in the physical education classes and through the school cafeteria programs. Most were aware that policies related to wellness were mandated but did not know what the policies entailed. They overwhelmingly indicated that teachers, parents, community members and experts in nutrition should be involved in the policy making decisions. This study revealed that although many schools have wellness policies, not all personnel were knowledgeable about the details or its implementation. It is recommended that school districts provide a platform to educate personnel of the wellness policies thus making it easier to implement at the local school levels. Funding was made possible (in part) by Grant # 1P20MD0002295 from the National Center on Minority Health and Health Disparities
Food Insecurity and Healthcare Expenditures in Older Adults: Georgia Advanced Performance Outcomes Measures Project 2008 (GA POMP)
Authors: Lee Jung Sun , Bhargava Vibha , Jain Rahul , Johnson Mary Ann , Brown Arvine
Published: June 2021

Food insecurity is a persistent, growing, and clinically relevant problem in older adults, however its impact on healthcare expenditure is not known. This study examined the relationship of food insecurity with Medicare and out‐of‐pocket (OOP) expenditures in older Georgians enrolled in Medicare and meals services using two complementary datasets, GA POMP and 2008 Medicare claims data (n=903, mean age 76.9±7.8, 31.0 % male, 64.2% white). Due to the mixed distribution of healthcare expenditure data (e.g., high non‐users, right skewed distribution for users), two‐part models were used. More than half of the sample were food insecure (50.4%) and they were more likely to report poorer health status and to have chronic diseases than food insecure individuals. Food insecure older adults were less likely to incur any Medicare expenditure, but not any OOP expenditure than their counterparts. Among those who had any positive expenditure, food insecure compared with food secure individuals had similar Medicare expenditures, but lower OOP expenditures. In 2008, adjusted mean Medicare and OOP expenditures of food insecure individuals were $1,875 and $310 less than food secure individuals, respectively. These findings suggest complex relationships between food insecurity and healthcare expenditures in older adults reflecting unique healthcare access and usage patterns. This study was funded in part by US AoA and UGA.
Enhanced Metabolic Inactivation of PGE2 by Selenium in Macrophages is Mediated by the Up regulation of 15‐hydroxy‐prostaglandin dehydrogenase
Authors: KAUSHAL NAVEEN , Narayan Vivek , Patterson Andrew D , Prabhu Kumble Sandeep
Published: June 2021

15‐hydroxy prostaglandin dehydrogenase (15PGDH) is a prostaglandin‐degrading enzyme, which regulates the biological functions of pro‐inflammatory PGE2 leading to the formation of an inactive metabolite, 13,14‐dihydro‐15 keto PGE2. Recent and past studies in our laboratory have indicated the ability of micronutrient antioxidant selenium (Se) to regulate the production of PGE2, while increase the production of PGD2 arm of the arachidonic acid pathway, where selenoproteins play a pivotal role. The shunting of PGH2 to PGD2, instead of PGE2, upon endotoxin challenge by selenoproteins involves complex regulatory circuits involving the upregulation of H‐PGDS accompanied by the downregulation of mPGES‐1, which catalyzes the production of PGE2. Here we demonstrate the ability of Se to upregulate the expression of 15PGDH in a dose‐dependent manner in a murine macrophage model. Treatment of cells with sodium selenite increased the expression of 15PGDH mRNA; while those treated with organo‐Se compounds failed to upregulate 15PGDH suggesting the essential role of selenoproteins. Given that upregulation of 15PGDH is a critical component in the resolution of inflammation, we discuss the implication of upregulation of 15PGDH by Se in a DSS‐induced model of ulcerative colitis.

Grant Funding Source: NIH DK077152
Effects of Ferulic Acid Supplementation on Lipid Profiles, Oxidative Stress and Inflammatory Status in Hypercholesterolemic Subjects
Authors: Bumrungpert Akkarach , Pingeesakikul Tuangsap , Tirawanchai Nednapis , Tuntipopipat Siriporn , Lilitchan Supathra , Komindr Surat
Published: June 2021

Ferulic acid is the most abundant phenolic compound found in vegetables and cereal grains. In vitro and animal studies have shown that ferulic acid has anti‐hyperlipidemic, anti‐oxidative and anti‐inflammatory effects. The objective of this study was to investigate the effects of ferulic acid supplementation on lipid profiles, oxidative stress, LDL‐C oxidation and inflammatory status in hypercholesterolemia subjects. The study design was a randomized, double‐blind, placebo‐controlled trial. Volunteers with hypercholesterolemic were randomly divided into 2 groups. The treatment group (n = 24) was given ferulic acid and the control group (n = 24) was provided placebo 500 mg twice a day for 6 weeks. Ferulic acid supplementation demonstrated a statistically significant decrease of total cholesterol (8.1%), LDL‐C (9.3%), triglyceride (12.1%) and increase of HDL‐C (4.3%) compared with the placebo group. Ferulic acid also significantly decreased d‐ROMs (11.7%), MDA (24.5%) and increased BAP (11.8%), biomarkers of oxidative stress. Moreover, oxidized LDL‐C was significantly decreased in the ferulic acid group (7.1%) compared with the placebo group. In addition, ferulic acid supplementation demonstrated a statistically significant reduction of the inflammatory markers, hs‐CRP (32.66%) and TNF‐alpha (13.06%). These data suggest that ferulic acid supplementation could decrease the risk factors of cardiovascular disease. (Supported by National Research Council of Thailand)
Impact of dietary calcium concentrations on growth, bone development and the behavior of mesenchymal stem cells in neonatal piglets
Authors: Li Yihang , Seabolt B S , Stahl C H
Published: June 2021

The impact of dietary Ca on bone is well described in growing and mature mammals; however, less is known about Ca nutrition during the neonatal period. In order to further characterize the effects of neonatal Ca nutrition, we conducted a 14d Ca dose response feeding trial with 24 piglets (28±6 h of age). Pigs were limit fed liquid diets, containing either deficient, adequate, or excessive amounts of Ca (0.6, 0.9 or 1.3% Ca on a DM basis), in order to match the growth rate of sow‐reared controls. Blood was collected at d7 and d14 for determination of indicators of Ca status, and bones were collected for mineral content determination and for the isolation of MSC on d14. In vivo MSC proliferation was determined by an oral dose of BrdU 12h before tissue collection. Ca deficiency decreased growth rate, bone mineral content, and urinary Ca excretion (P<0.05). Excess dietary Ca had no effect on growth rate, but numerically increased bone mineral content, and increased (P<0.05) urinary Ca excretion compared to the Ca adequate group. Circulating PTH decreased (P<0.05) with increasing dietary Ca. Proliferation of MSC was greatest (P < 0.05) among pigs fed excess Ca. In vitro differentiation capabilities of MSC were significantly impacted based on Ca nutrition. The data suggest that neonatal Ca nutrition impacts bone development and may have long‐term consequences for bone health due to programming effects on MSC.
Regulated metabolism of Vitamin A by retinol dehydrogenase 10 is critical for embryonic development of the heart
Authors: Sandell Lisa L
Published: June 2021

Congenital heart disease is a serious human health issue, affecting as many as 1% of live births. For most cases of cardiac birth defect the cause is unknown, reflecting the limitations of our understanding of which environmental agents, genetic factors, and gene‐environment interactions contribute to cardiac abnormalities. The purpose of the current study is to investigate the mode whereby an embryo converts Vitamin A into the potent morphogen retinoic acid and to understand how disturbances in the production of retinoic acid may contribute to developmental malformations of the heart. Precise regulation of retinoic acid production is critical ‐ either excessive or insufficient levels result in cardiac birth defects ‐ yet very little is known about the mechanism whereby this process is controlled. We have demonstrated that the short chain dehydrogenase/reductase RDH10 is the primary enzyme responsible for the first step of embryonic Vitamin A metabolism. We show that embryos with mutations in Rdh10 have severe cardiac developmental abnormalities, including defects in heart looping, myocardial growth, aorticopulmonary septation and morphogenesis of the atria. Using transgenic reporter mice and RNA in situ hybridization we have determined that the Rdh10−/− cardiac phenotypes are associated with abnormal expression of Hox family A‐P patterning genes and also with defects in cell adhesion and abnormal distribution of extracellular matrix molecules. Finally, utilizing quantitative reverse transcriptase PCR we have demonstrated that Rdh10 gene transcription is a point for feedback control in regulation of retinoic acid production. These data suggest that Rdh10 may be a candidate gene for association with human cardiac abnormalities. Moreover, the data shed light on the molecular mechanism whereby disruptions in Vitamin A metabolism may contribute to congenital heart disease.

Grant Funding Source: NIH‐COBRE
Race, diet, and body size contribute to skeletal parameters in female adolescents
Authors: Martin Berdine , Whisner Corrie , Delany Lauren , Weaver Connie
Published: June 2021

Multiple parameters contribute to achieving peak bone mass especially during the adolescent growth spurt. Few studies have characterized the association of race/ethnicity, diet, and anthropometric characteristics with skeletal bone mineral content (BMC) of teen girls. This study analyzed data collected from a female multi‐racial population, age 11–15, who participated in 11 residential metabolic studies over a 20 year period. Bone parameters and body composition were measured by dual energy X‐ray absorptiometry (DXA). Habitual dietary intake was based on 3–9 day food records collected before the initiation of the studies. While body size and sexual maturation explained a major portion of the variation in total body BMC, race/ethnicity and diet explained 11 and 9%, respectively when considered as separate variables. When adjusted for body size, sexual maturation, and habitual dietary intake black female teens exhibited greater total body BMC than white, Asian, or Mexican American teens. Racial differences in BMC varied by skeletal site but race/ethnicity and variables representing body size, sexual maturation and diet remained significant at each site. Supported by NICHD RO1HD061908.
Relationship between Executive Function, Mood, and Eating Behavior in Preschoolers
Authors: Pieper Joy , Laugero Kevin
Published: June 2021

Decreased executive function has been linked to unhealthy eating behaviors and obesity in older children and adults, however little is known about this relationship in young children. The purpose of this research was to first determine this relationship, and second, to explore whether mood and emotional reactivity are related to executive function and/or eating behaviors. We conducted a pilot study in a research‐based preschool at the University of California‐ Davis with 30 three to five year‐old children. Executive function was measured via four tasks: flanker, task‐switching, delay of gratification, and the Children's Gambling Task. An eating in the absence of hunger (EAH) task was used to determine nonhomeostatic eating behavior, and parents filled out the Child Eating Behavior Questionnaire. Mood and emotional reactivity ratings were determined via parental reports on the Children's Behavior Questionnaire as well as direct measures of the children's mood and emotional reactivity with a visual analog scale, salivary cortisol and alpha‐amylase, and skin conductivity. Children who scored higher on the Children's Gambling Task ate significantly fewer calories from cookies in the EAH task. Higher scores on the task switching task, however, were associated with significantly more total calories consumed in the EAH task. No measures of mood or emotional reactivity were significantly related to calories consumed in the EAH task. Childrensˈ reports of mood prior to the Children's Gambling task were inversely related to performance on the task, such that a more negative mood was associated with riskier behaviors. Further studies are necessary to determine whether early interventions to improve executive function may also have the benefit of improving eating behaviors and decreasing risk of obesity in the long run.

Grant Funding Source: USDA‐WHNRC, UC Davis Jastro Graduate Student Research Award
A one year high protein, low fat weight loss diet improves body composition and cardiometabolic risk factors in overweight males
Authors: Wycherley Thomas , Brinkworth Grant , Clifton Peter , Noakes Manny
Published: June 2021

Objective

To evaluate the effects of two energy matched, low fat, hypocaloric diets differing in carbohydrate to protein ratio, on body composition and cardiometabolic health outcomes in overweight males.

Methods

120 males (age 50.8±9.3 yrs, BMI 33.0±3.9 kg/m2) were randomly assigned to a low fat, isocaloric, energy restricted diet (7MJ/day) with either high protein (HP; Pro:Carb:Fat % energy, 35:40:25) or standard protein (SP; 17:58:25). Body weight, body composition, and cardiometabolic risk factors were assessed at baseline and after one year.

Results

68 participants completed the study (HP n=33; SP n=35). Both groups experienced similar reductions in body weight (HP −12.3±8.0 kg [−12%]; SP −10.9±8.6 kg [−11%]) and fat mass (HP − 9.9±6.0 kg [−27%]; SP −7.3±5.8 kg [−22%]), P>0.11 time x group. Participants who consumed the HP diet lost less fat free mass (−2.6±3.7 kg [−4%] vs. −3.8±4.7 kg [−6%]), P<0.01. Both groups experienced a similar overall increase in HDL cholesterol (8%) and reductions in total cholesterol (−7%), LDL cholesterol (−9%), triglycerides (−24%), glucose (−3%), insulin (−38%), blood pressure (−7/−12%) and C‐reactive protein (−29%), P≥0.14.

Conclusions

In overweight and obese males, a HP and SP diet similarly reduce body weight and improve cardiometabolic health outcomes. A HP diet was more effective for improving body composition.

Research support provided by Meat and Livestock Australia.
Serum 25‐hydroxyvitamin D and breast cancer in the military: A nested case‐control study
Authors: Mohr Sharif Burgette , Gorham Edward D , Alcaraz John E , Kane C I , Macera Caroline A. , Parsons J Kelley , Wingard Deborah L , Horst R , Garland C F
Published: June 2021

The objective of this study was to test whether a relationship exists between prediagnostic serum levels of 25‐hydroxyvitamin D (25(OH)D) and risk of breast cancer in a U.S. military cohort. 600 incident cases of female breast cancer were matched to 600 controls in a nested case‐control study. Conditional logistic regression was used to test the relationship of 25(OH)D to breast cancer risk, controlling for race and age. There was an inverse association between serum 25(OH)D and odds of breast cancer that did not reach statistical significance overall. However, in pairs of white women (N = 122 pairs) whose blood was drawn < 90 d before diagnosis, those in the highest quintile of serum 25(OH)D had 70% lower estimated risk of breast cancer (odds ratio 0.30, 95% confidence interval 0.12–0.74, p < 0.01) compared to those in the lowest. The quintile cut points were < 15, 15–21.7, 27.4–35.1, and > 35.1 ng/ml. In this cohort, the timing of the inverse association of serum 25(OH)D with risk of breast cancer suggests that the effect of serum 25(OH)D on risk of breast cancer is strongest during a critical interval preceding diagnosis, although reverse causation should be ruled out. A model based on anti‐angiogenesis is described. Further research, including cohort studies of serum 25(OH)D status with breast cancer risk and timing, should be performed to confirm this association.
Nutrition education and cooking classes with teen and adolescent mothers
Authors: Scripa Ioana , Dobson Christina , Yamaguchi Erica , Taylor Martha
Published: June 2021

A pilot study evaluated the effect of nutrition education and cooking classes on nutrition knowledge, cooking knowledge, self‐efficacy towards cooking and healthy eating, and dietary habits of young mothers enrolled in life‐skill classes at the YWCA of Greensboro. This feasibility study is a two condition (group 1, and group 2) repeated measures (pretest, posttest, and follow‐up) design. The project used a convenience sample of 15 young mothers enrolled in the Teen Parent Mentor Program and Healthy Moms Healthy Babies program at the YWCA. Seven nutrition education and cooking classes were conducted at the YWCA facility as part of their programming. Class topics included information on kitchen safety/ sanitation, how to read a food label, fats, how to shop on a budget, portion control, meal planning, and feeding your child. Mothers helped prepare weekly recipes that included fruits, vegetables, and whole grains. Women received all educational handouts and recipes. Sixty‐four percent of the participants found the class topics in general to be very helpful, while 73% found the cooking activities to be very helpful. Also, 67% of them affirmed that the handouts were very helpful. Findings of this study will be used to continue develop culturally relevant nutrition interventions to improve the nutrition knowledge, eating habits, and cooking skills of young mothers in community‐based environments
Coordinated response of the fat and cellular content of breastmilk to the degree of fullness of the breast
Authors: Hassiotou Foteini , Filgueira Luis , Hepworth Anna , Trengove Naomi , Lai Ching Tat , Hartmann Peter
Published: June 2021

Breastmilk contains an array of biochemical and cellular components that provide nutrition and protection to the infant. It has been previously known that pre‐feed milk has lower fat and cell contents compared to post‐feed milk. To further elucidate the relationship between the degree of fullness of the breast and the fat/cell milk content, we collected 5 mL of milk from 6 breastfeeding women at specific time points around the first morning feed (immediately prior and after the feed, and then every 30 min for the next 3 hours). Each participant repeated this 2–4 times on different days. A 24‐hour milk production measurement allowed calculation of the degree of fullness of the breast at each time point. Cell viability was high in all samples (92±0.3%). Fat content varied from 1.3% (when the breast was full) to 16.6% (when the breast was empty), and similarly, cell content varied from 10.6×103 to 3.9×106 viable cells/mL milk. Remarkably, a concurrent response of fat and cell contents to the degree of fullness of the breast was observed. Although post‐feed milk had higher fat and cell contents compared to pre‐feed milk, as known previously, even higher fat and cell contents were obtained 30 min after the feed, with gradual reduction to return to pre‐feed levels at 3+ hours post‐feed. Ongoing work is examining the mechanisms behind this phenomenon and potential concurrent changes of biochemical and cellular breastmilk composition.

Grant Funding Source : Women and Infants Research Foundation, Medela AG
ZnT4 transports zinc to critical zinc‐dependent proteins in the trans‐Golgi network and exports Zn across the cell membrane in mammary epithelial cells
Authors: McCormick Nicholas , Kelleher Shannon L
Published: June 2021

The benefits of breastfeeding include optimized growth, neurological development and immune function in infants. However, sub‐optimal lactation occurs in ~15% of women and results in reduced milk volume, compromised milk composition or lactation failure. A mutation in the gene encoding ZnT4 (SLC30A4) is associated with sub‐optimal lactation in mice. These mice have smaller mammary glands (MG), decreased milk synthesis and ~35% less Zn secreted into milk. We hypothesized that ZnT4 plays a critical role in MG function. Genetic manipulation of ZnT4 abundance in mammary epithelial cells was positively correlated with Zn secretion. ZnT4 transported Zn into a labile Zn pool in the trans‐Golgi network (TGN) where it was made available for Zn‐dependent proteins. This was evidenced by ZnT4 attenuation which decreased carbonic anhydrase VI expression, and ZnT4 over‐expression which decreased galactosyltransferase activity. Additionally, ZnT4 exported Zn directly across the cell membrane. In summary, ZnT4 has a dual role involving 1) labile Zn accumulation in the TGN providing Zn to Zn‐dependent proteins; and 2) Zn transport across the cell membrane into milk. Our studies suggest that ZnT4 provides Zn to proteins critical for secretion and mammary gland function, thus understanding factors that regulate ZnT4 is important to increasing the incidence of lactation and improving the health of women and children.

Grant Funding Source: NIH R01 HD058614
Participant utilization and satisfaction with fruits, vegetables and jarred baby foods in the new Supplemental Nutrition Program for Women Infants and Children (WIC) food package
Authors: Kim Loan Pham , Whaley Shannon S. , Harrison Gail G.
Published: June 2021

In 2009 the WIC program made a major revision to the food package, representing a significant change in the resources available to improve diet quality for 50% of all infants born in the United States and their mothers. This study extends findings from a state‐wide survey of WIC participants which found the addition of fruits, vegetables and jarred foods to the infant food package was well received overall by participants. As babies got older, however, caregivers preferred the option to choose between jarred baby foods and cash value vouchers (CVV) for fruit and vegetable in order to prepare their own baby foods. The present study further examined cultural variations and preferences using qualitative methods. One‐on‐one interviews were conducted with participants from 5 ethnic groups (n = 47). The narratives revealed variations in feeding practices among latino, Vietnamese and Chinese participants, and thus caregivers’ utilization and satisfaction with the fruit and vegetable CVVs and jarred baby foods. We will suggest that ethnic group differences in infant feeding practices should be considered with regards to the new WIC food package.
Contribution of leading food sources, meals and presentations to dietary intake in government sponsored day‐care centers in Guatemala (SOSEP)
Authors: Hernández Liza , Montenegro-Bethancourt Gabriela , Kim Lydia , Bermudez Odilia I , Vossenaar Marieke , Solomons Noel
Published: June 2021

Objective

To determine the leading food sources of nutrients, principal mealtimes, and predominant presentation (solid/liquid) provided by the diet served in government sponsored day‐care centers (SOSEP).

Methods

The SOSEP 8‐week rotating menu, containing 102 items, was reduced to the content in gravimetric or IU units for 30 selected nutrients per menu cycle. The item, meal type (breakfast {B}/lunch {L}/snacks {S}) and presentation (solid/liquid) were ranked highest for each nutrient.

Results

5 items were the leading sources of 19/30 nutrients of interest (vegetable oil, 5; table sugar, 4; corn tortilla 4; oatmeal, 3; Incaparina®, 3). An additional 9 items were leading sources for 2 or 1 item each. 4 main items were of animal origin. L was the predominant source for 25 nutrients, B for 5, and S for 2 (2 nutrients were tied across 2 meal types). The solid form was predominant for 26 nutrients, and liquid for 6 (2 nutrients were tied across forms).

Conclusions

Number‐1 predominance of nutrient delivery to the SOSEP diet is limited to a few items, mostly of plant origin. As expected for Guatemala, L was the main meal type for most nutrients, which derived from solid foods.
New diagnostic approaches mediated by oligonucleotide aptamer (a revolutionary antibody?)
Authors: Zu Youli , Zeng Zihua , Zhang Peng
Published: June 2021

Aptamers, a class of small molecule ligands composed of short single‐stranded oligonucleotides, have emerged over the last several decades. Theoretically, the low nanomolar binding affinities and exquisite specificity of aptamers for their targets make them a versatile probe for disease diagnosis. In addition, the absence of immunogenicity or toxicity of aptamers makes them suitable also for in vivo use. However, their potential clinical value has not yet been explored. To investigate new aptamer‐mediated diagnostic approaches: 1) a tumor biomarker‐specific aptamer was synthesized and conjugated with fluorescent reporter for multi‐color flow cytometry. Comprehensive immunophenotyping of lymphoma cells by using aptamer probe showed identical cell binding pattern to that by a standard antibody. 2) to study formalin‐fixed and paraffin‐embedded tissues the aptamer was biotinylated for HRP‐streptavidin visualization system. Immunostains revealed that the aptamer specifically detected lymphoma cells with shorter probing time and less background staining in tumor tissues than antibody. 3) a real time tumor imaging was performed using a mouse model. Systemic administration of aptamer selectively highlighted lymphoma tumor, but not control tumor in the same mouse. In summary, our studies show first evidence that synthetic oligonucleotide aptamer are useful for both in vitro and in vivo tumor diagnosis.
The α7‐nicotinic receptor antagonist induces robust apoptosis in human SCLC
Authors: Brown Kathleen C. , Lau Jamie K. , Dom Aaron M. , Shiflett Brandon S. , Witte Theodore R. , Hardman W. Elaine , Luo Haitao , Chen Yi Charlie , Carpenter A. Betts , Dasgupta Piyali
Published: June 2021

Small cell lung cancer (SCLC) is characterized by rapid progression, early metastasis and low survival rates. Smoking is correlated to 90% of all reported SCLC cases, suggesting that tobacco components like nicotine contribute to the pathophysiology of this disease. Nicotine promotes the proliferation of human lung cancer cells via nicotinic acetylcholine receptors (nAChRs). Our data shows that long‐term exposure to nicotine stimulates the growth of the human SCLCs via the α7‐nAChR subtype. Therefore, we hypothesized that α7‐nAChR antagonists should be useful in attenuating the growth of human SCLCs. We observed that the small molecule α7‐nAChR antagonist MG624 induced robust apoptosis in human SCLC cells as measured by TUNEL and caspase‐3 cleavage assays. Furthermore, the administration of MG624 suppressed nicotine‐induced growth of H69 human SCLC xenografts in chicken chorioallantoic membrane and in athymic mice models. Immunohistochemical staining of the H69 tumors isolated from MG624‐treated athymic mice showed extensive apoptosis. Our data suggest that MG624 may have potential applications for the treatment of human SCLCs.
Fibroblast growth factor (FGF) 5 can inhibit the growth of hepatocellular cell line
Authors: YEH BYUNG IL , Namkung Jun , Jung Yu Jung , Rhee Sangmyung
Published: June 2021

We completed the quantitative profiles of FGFs and FGFRs in hepatocellular carcinomas (HCC) and hepatoblastomas compared with normal liver cells in the previous study. Several FGFs including FGF5 and its functional receptors were hightly expressed in hepatocellular carcinoma cell lines even though the FGFs are not checked from normal liver cDNAs. As FGF5 are known to have the mitogenic and cell survival activity in the cancer, we studied to check the inhibition effect for hepatocellular carcinogenesis by interfering FGF5 activity with its siRNAs in the HCC cell lines.

We knocked down the level of FGF5 using siRNA technology and measured the extent of cell proliferation and apoptosis in HepG2 cells. We checked the Erk1/2 activity in the FGF5 silencing cells comparing to that of control cell. We also investigated the addictive effect of FGF5 silencing on the cytotoxicity in the combination treatment of anti‐cancer drug, Cisplatin.

FGF5 silencing in HepG2 cell lines caused profound decrease the cell viability and Erk activation upon the serum stimulation. Cisplatin treatment in the FGF5 silencing cells showed dramatic increase the cytotoxicity resulting in the cellular apoptosis.

These results showed that hapatocellular carcinogenesis may due to specific expression of several FGFs and its counterpart receptors. We also propose impairment of FGF5 function in the HCC may critical for liver cancer therapy.
Vitamin D supplementation and insulin sensitivity in early pubertal children: results from the randomized controlled GAPI trial
Authors: Ferira Ashley Jordan , Laing Emma , Hausman Dorothy , Hall Daniel , Weaver Connie , McCabe George , Martin Berdine , Peacock Munro , Warden Stuart , Hill Kathleen , Lewis Richard
Published: June 2021

The dose‐response effect of vitamin D supplementation on insulin sensitivity was examined in healthy early pubertal children (aged 9–13 y), in the Georgia, Purdue, and Indiana University School of Medicine (GAPI) trial. 320 black and white males and females participated in this 12‐week triple‐masked, placebo‐controlled trial. Subjects were randomized to receive placebo or vitamin D3 (400, 1000, 2000, or 4000 IU/d). Anthropometry, pubertal maturation, body composition, dietary intake, and fasting biochemical indices (glucose and insulin) were assessed. Main time effects were significant (all p<0.004): glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA‐IR) increased, while quantitative insulin sensitivity check index (QUICKI) decreased. The effects of vitamin D supplementation over time were non‐significant for glucose (p=.780), insulin (p=.918), HOMA‐IR (p=.883), and QUICKI (p=.905). We report findings from the first pediatric vitamin D trial to examine insulin sensitivity. Our subjects’ pubertal, normo‐glycemic, and vitamin D sufficient status may explain our null findings. Future research should examine high‐risk pediatric populations, particularly during post‐puberty. Supported by NICHD RO1HD057126 and Allen Foundation grant 2.008.319.

Grant Funding Source: NICHD
Alcohol Exposure and Burn Injury Drive Acute Adipose Inflammation and Alterations in Glucose Transporter GLUT1
Authors: Qin Yuanyuan , Bird Melanie , Chen Micheal , Kovacs Elizabeth , Makowski Liza
Published: June 2021

Macrophages are central to the formation of obesity. Alcohol is a dietary modulator of the inflammatory response. The objective was to examine the role of inflammation in adipose tissue during trauma after an acute alcohol exposure. Mice were first exposed to saline or intraperitoneal ethanol (1.12g/Kg) and then subjected to a 15% total body surface area scald or sham injury 30 minutes later. qPCR and Bio‐plex protein arrays were used to evaluate the inflammatory response in serum and gonadal adipose. Alcohol alone caused little induction of inflammation in adipose over sham‐vehicle. Burn induced minimal elevations in interleukin‐6 (IL‐6) with dramatic elevations detected after combined acute alcohol and burn injury compared to either exposure alone or control. Serum IL‐6 levels were also elevated by burn, and 33% further induced with burn and alcohol exposure together. In addition, neutrophil chemokine KC (CXCL1), MCP‐1, and glucose transporter GLUT1 were dramatically increased in adipose tissue after burn trauma and further elevated after combined acute burn and ethanol exposure relative to either insult alone. Taken together, data suggest that the pro‐inflammatory response in adipose may play a role in systemic response to injury which is exacerbated upon alcohol exposure. R00 AA017376

Grant Funding Source : NIH‐NIAAA
A prospective study of blood pressure, BMI and immunity in breastfeeding and formula feeding women
Authors: Groer Maureen Wimberly , Sahebzamani Frances , Jevitt Cecilia , Beckstead Jason
Published: June 2021

The aims of this study were to follow trajectories of physiological variables across the postpartum and to determine if these variables differed by lactational status. Seventy health postpartum women were studied 7 times through the sixth postpartum months. Blood pressure, heart rate, and BMI were measured at each time point, along with demographic, lifestyle, stress and mood measures. Plasma cytokines and cytokines from mitogen stimulated ex vivo whole blood cultures, Natural Killer cell cytotoxicity, and plasma hormones were also measured. Results indicated significant differences in blood pressure and BMI for both exclusive and partial breastfeeders compared to formula feeders across time. Plasma and culture supernatant cytokines showed lower IL‐6 in breastfeeders. Dysphoric moods and stress perceptions were also lower in breastfeeders. Since lactational history is associated with reduced risk for a number of cardiovascular and metabolic midlife diseases, exploration of the systemic physiology of lactation may provide clues to mechanisms.

Supported by NIH RO1‐NR05000
Ontogeny of Mechanosensation During Vascular Development
Authors: Jones Elizabeth A.V. , Henderson-Toth Caitlin
Published: June 2021

Endothelial cells have the capacity to sense hemodynamic forces through the process of mechanotransduction. When blood flow starts in the embryo, many of the components required for sensing hemodynamic forces in the adult have not yet formed. We recently showed that hemodynamic forces were required for normal vascular development. In this work, we have been focusing on the development of a mechano‐sensory complex by studying the development of the glycocalyx. The glycocalyx forms extensions into the vascular lumen that are anchored directly to actin stress fibres of the cytoskeleton and transmit hemodynamic signals. By electron microscopy and immunohistochemical staining, we show that the glycocalyx is present as soon as blood flow starts. We then used selective enzymatic degradation to look at whether the glycocalyx has a functional role during vascular development. We found that during development, hyaluronan, but not other glycocalyx components, affected vascular permeability. We also found that degradation of heparan sulfate resulted in decreased expression of a subset of mechanotransduced genes.
Control of centrosomes and kinetochores by telomeres in meiosis
Authors: Cooper Julia Promisel , Bez Cécile , Fennell Alex , Klutstein Michael , Tomita Kazunori
Published: June 2021

While telomeres have well‐studied roles in preserving the integrity of chromosome ends, they play radically different and fundamentally important roles in meiosis; understanding these roles will not only shed light on mechanisms ensuring successful sexual reproduction but also on mitotic growth. During meiotic prophase, all the telomeres in the cell cluster at the nuclear periphery to form the highly conserved ‘bouquet’ structure. The fission yeast bouquet associates with the spindle pole body (SPB; the fission yeast centrosome equivalent) and can be specifically disrupted by mutating telomere proteins or meiosis‐specific proteins that connect the telomere complex with the SPB, allowing functional analysis. We have shown that the bouquet is required for proper meiotic spindle formation (Tomita & Cooper, Cell 2007). We find that while the SPB duplicates properly in the absence of the bouquet, the duplicated SPBs often fail to separate and show defects γ‐tubulin complex (γ‐TUC) localization to the spindle poles, suggesting that the bouquet modifies an SPB protein that controls γ‐TUC recruitment. Bouquet‐defective cells can overcome these challenges and form proper meiotic spindles if their SPBs become transiently associated with nontelomeric heterochromatin during meiotic prophase, highlighting the importance of chromatin‐SPB interactions for promoting spindle formation. Finally, we present data leading to the provocative idea that the bouquet influences meiotic kinetochore assembly and centromere‐spindle attachment.