bluuebunny/crossref_metadata_2025 huggingface dataset:
The 2008 Feeding Infants and Toddlers Study (FITS): Parents' perceptions and practices related to diet and weight
Authors: Briefel Ronette , Deming Denise , Fox Mary Kay , Condon Elizabeth , Reidy Kathleen
Published: June 2021

National data from the 2008 Feeding Infants and Toddlers Study (FITS) were analyzed to assess parents' perceptions of their children's diet and weight, and adherence to Healthy Active Living for Families recommendations for diet, physical activity, and screen time. Household interviews and 24‐hr dietary recalls were conducted by telephone w/parents or primary caregivers of infants 0–11 mo (n=887), toddlers 12–23 mo (n=925), and preschoolers 24–47 mo (n=1,461) (total n=3,273). Most parents think their child consumes enough fruits and vegetables, however, 1 in 4 preschoolers did not consume any distinct fruit and 1 in 3 did not consume any vegetable; almost half of toddlers (44%) and preschoolers (48%) consumed sugar‐sweetened beverages on a given day. Most parents considered their child's weight to be ‘about right’, but parents were 3–4 times more likely to think their child was underweight (8–9%) than overweight (2–3%) – a finding inconsistent with national U.S. data showing that 3% of 1–4 year olds are underweight and 10% are overweight. One in 4 preschoolers exceeded recommendations to limit screen time to 2 hrs or less per day, and 1 in 4 watched TV or videos in the room where they sleep. FITS data indicate that the toddler and preschool period is a critical time to help parents instill healthful, long‐term dietary and activity behaviors in their children and family to prevent childhood obesity. Research funded by Nestlé.
Multi‐vitamin supplementation during pregnancy alters in utero development of CD‐1 mice offspring
Authors: Szeto Ignatius Man Yau , Cho Daniel , Okubo Nobuhiko , Reza‐Lopez Sandra A. , Duan Jiuhua , Huot Pedro S.P. , Ward Wendy E. , Anderson G. Harvey
Published: June 2021

The effects of multi‐vitamin supplementation during pregnancy in CD‐1 mice on body weight, glucose regulation and the expression of appetite‐regulatory genes in the hypothalamus of the offspring were investigated. Pregnant dams were fed the AIN‐93G diet containing the recommended (1V), 2.5‐fold (2.5V) or 5‐fold (5V) the vitamin content during gestation. Offspring were weaned to a high‐fat obesogenic diet, and sacrificed at weaning or at 13 wk post‐weaning. No difference in birth weight or litter size was observed. Body weight (BW) and body fat were similar among groups at 13 wk post‐weaning. The 5V compared with the 1V gestational diet led to greater glucose disposal and insulin sensitivity, and bone mineral content relative to BW in offspring at 10 wk post‐weaning. It also resulted in lower expression of the leptin receptor (LepR), agouti related‐peptide (AgRP), and neuropeptide Y (NPY), but not pro‐opiomelanocortin (POMC), in both male and female pups at weaning. At 13 wk post‐weaning, LepR and NPY in males, AgRP in females, and POMC in males and females were lower. The 2.5V gestational diet reduced expression of LepR in both sexes and POMC in females. Cocaine‐and‐amphetamine‐regulated transcript (CART) expression was unaffected by the gestational diets. In utero development of regulatory processes are affected by modest increases in the vitamin content of the mouse diet during gestation.

Grant Funding Source: Canadian Institutes of Health Research (CIHR) ‐ Institute of Nutrition, Metabolism and Diabetes (INMD), OOP# 77980
Maternal DHA Supplementation Attenuates Newborn Hyperoxia‐Induced Lung Developmental Deficits into Early Adulthood
Authors: Rogers Lynette K , Dingess Kelly , Velten Markus , Heyob Kathryn , Valentine Christina J
Published: June 2021

Newborn mice exposed to hyperoxia demonstrate decreased alveolarization similar to preterm infants with bronchopulmonary dysplasia. We tested the hypothesis that docosahexanoic acid (DHA) administration to pregnant and nursing dams would decrease inflammatory responses and improve lung function. Dams were fed purified control or DHA‐supplemented diets beginning at E16. After birth, the pups were exposed to >85%O2 or room air (RA) for 14 days, then returned to standard diets and RA until 28 days. Lung development was assessed by morphometric analyses and pulmonary function. Protein levels of COX‐2 and sRAGE were analyzed by western blot. Mice receiving DHA and hyperoxia exposure during the newborn period demonstrated increased alveolarization (alveolar number, 103 vs 65; alveolar area, 1516 vs 2058 microns2) and improved lung function (tissue elastance, 24.9 vs 32.0 ml/cmH2O; tissue compliance, 0.042 vs 0.035 ml/cmH2O) compared to control diet, hyperoxia exposed mice. Levels of COX‐2 and sRAGE were higher in pups exposed to hyperoxia but were attenuated by DHA supplementation. Neonatal hyperoxia exposure caused sustained lung deficits in adulthood that were lessened by DHA supplementation and may be mediated through RAGE or COX‐2 signaling pathways. We speculate that maternal DHA supplementation will be beneficial in preventing lung disease in premature infants. Supported by ATS unrestricted grant.
Intrauterine Growth Restriction‐Associated Increase in Lung Elastin is Due to Protein Deficiency
Authors: Rehan Virender K. , Li Yishi , Sakurai Reiko , Torday John
Published: June 2021

Objectives

To determine 1) if increased lung elastin in intrauterine growth restricted (IUGR) infant is due to altered alveolar interstitial fibroblast (AIF) differentiation and 2) the specific nutrient deficiency that leads to increased elastin gene expression in the IUGR infant lung.

Methods

Pregnant rat dams were fed ad lib or on 50% food‐restricted diet. The pups were killed at 9 months and lungs were examined for elastin gene expression (RT‐PCR and Western blotting). Primary rat lung fibroblasts were cultured in DMEM ± fetal bovine serum (FBS), Vitamin D (VD), arachidonic acid (ARA) +doxohexanoic acid (DHA), or bovine serum albumin (BSA)‐ then the expression of elastin and activation of mTOR signaling were examined.

Results

With food restriction there was a significant increase in elastin gene expression. Culturing primary AIFs without FBS significantly increased the expression and protein levels of various elastin‐related genes, accompanied by mTOR activation. FBS‐restriction associated increase in elastin expression and mTOR activation were only partially blocked by VD and ARA+DHA, but completely blocked with BSA.

Conclusions

Elastin expression is significantly increased in the lungs of IUGR offspring; this increase is largely due to protein deficiency; and AIF mTOR signaling plays an important role in increased elastin levels in the IUGR offspring lung. (Grant: NIH (HD‐58948).
Demographic predictors of overweight and obesity among Colombian children and adolescents
Authors: Casanova Ines Gonzalez , Pratt Michael , Sarmiento Olga Lucia , Garcia Sandra , Stein Aryeh D.
Published: June 2021

We analyzed data for 15783 children ages 5 to 15 y from the Colombian 2005 National Nutrition Survey; computed overweight and obesity prevalence using WHO 2006, CDC 2000, and IOTF 2000 criteria; and compared the prevalence of combined overweight and obesity (Ow‐Ob) by age (5–10 vs 11–15 y), sex, residence (urban vs rural), and wealth quintile. The prevalences of Ow‐Ob in boys and girls were WHO: 15.7, 17.2%; CDC: 11.5, 13.7%; and IOTF 9, 13.1%, respectively. The prevalences of obesity in boys and girls were WHO: 3.8, 3.3%; CDC: 3.6, 3.5%; and IOTF 1.8, 1.9%, respectively. Among boys, the prevalence Ow‐Ob was 17.2% for ages 5–10 y and 13.4% in ages 11–15 y (P<0.01), using WHO criteria. Among girls, these prevalences were 15.0 and 19.7% (p<0.01; p for heterogeneity by gender <0.01). The prevalence was 18.5% in urban areas and 15.6% in rural areas (p<0.01) and increased across wealth quintiles (p for trend <0.01 for both boys and girls); yet, the greatest prevalence was observed among rural boys in the highest wealth quintile (34.7%). The prevalence of Ow‐Ob differed according to the criterion used, was higher among girls than boys and in urban as compared to rural areas, and patterns by age differed by sex. These differences may reflect differential effects by sex of cultural beliefs and puberty on behaviors associated with overweight. Funded by the CDC Foundation and CONACyT.
Characterizing beverage patterns among Alaska Natives living in rural, remote communities: the CANHR study
Authors: Bersamin Andrea , Herron Johanna , Nash Sarah , Maier Janne , Luick Bret
Published: June 2021

Caloric beverages, particularly sugar‐sweetened beverages (SSBs), have gained attention as a risk factor for obesity and its sequelae. The prevalence of obesity among AI/ANs exceeds the rates for all other ethnic groups, however little is known about beverage patterns in this group. Here, we characterize beverage intake among Yup'ik Eskimos and present public health and policy recommendations around beverage intake. Beverage and nutrient data, estimated with NDS‐R, are presented from 471 Yup'ik Eskimos (ages 14–92 years) who participated in the Center for Alaska Native Health Research (CANHR) Study. Beverages were classified as: Sugar sweetened soda and fruit drinks (SSBs), Artificially sweetened soda and fruit drinks (ASBs), Coffee, Tea, Milk, 100% juice, Other (beverages reported <10 times). Beverage patterns were strongly associated with age. Over 75% of beverages consumed by youth were SSBs, contributing on average 300kcals and 78g added sugar to daily intake. In contrast, SBBs represented less than 20% of beverage intake among older age groups. Intake of milk, 100% juice, and ASBs were low among all age groups. Reduction in SSB has the potential to reduce the burden of obesity in Yup'ik communities; a culturally and geographically relevant intervention, particularly one that takes a systems approach, should be pursued.

Supported by NIH grant (P20‐RR16430)
Growth patterns preceding mortality in the first 6 months of life among breastfed infants born to HIV infected women in Malawi
Authors: Brown Lauren Nami , Adair Linda S , Bentley Margaret E , van der Horst Charles M , Jamieson Denise J , Ellington Sascha R , Soko Alice , Kayira Dumbani , Chasela Charles
Published: June 2021

Poor infant nutritional status is a notable underlying cause of mortality. We examined growth patterns preceding death in 34 exclusively breastfed infants born to HIV infected women in the Breastfeeding, Antiretroviral and Nutrition study in Lilongwe, Malawi. Women were randomized to receive either a lipid‐based nutrient supplement during lactation or no supplement. These groups were further randomized to maternal antiretroviral (ARV) drugs, infant nevirapine or no postnatal ARVs. Infants were grouped by age at death (0< 1 mo, n=12; 1< 3 mo, n=11; and 3< 6 mo, n=11). These groups were compared to surviving infants using multinomial logistic regression. Low birth weight (LBW < 2.5 kg) strongly predicted early death (OR 10.27, 95% CI 3.27–32.27 in those 0–1 mo; OR 4.01, 95% CI 1.05–15.30) but not in the 3 < 6 mo group. Measures at regular follow‐up visits showed that lower mean weight, length, and BMI Z‐scores (based on WHO growth standards) more strongly predicted early death than they predicted death during 3< 6 mos. Declining anthropometric Z‐scores were evident in the weeks prior to death. Of the 34 infants who died, 8 were HIV infected and 5 of these 8 deaths occurred in 3< 6 mo. The analysis provides further evidence of the need to prevent LBW and optimize early growth in infants born in developing countries.

Supported by the Centers for Disease Control (U48‐DP000059‐01) and by the Bill and Melinda Gates Foundation (OPP53107).

Grant Funding Source: Centers for Disease Control (U48‐DP000059‐01) and by the Bill and Melinda Gates Foundation (OPP53107)
Production and Evaluation of Safety Index for Korean Children's Dietary Life
Authors: Kang Myung‐Hee , Hye‐Young P. Kim , Lee Jung‐Sug , Choi Young‐Sun , Kwark Dong‐Kyung , Chung Hae‐Rang , Choi Youn‐Ju , Lee Soon‐Kyu
Published: June 2021

This study was performed to produce and evaluate safety index for children's dietary life. The analytic hierarchy process (AHP) and Delphi method was used to develop evaluation indicators of the children's dietary safety. Three representative policy indicators, 9 strategy indicators and 20 detailed evaluation indicators were selected for the children's dietary safety index. Three representative policy indicators and nine strategy indicators are as followings: the children's food safety indicator (safety support by the local government, snack food safety control, institutional food safety control), the children's nutrition safety indicator (under‐nutrition and/or over‐nutrition control, snack food nutrition control, and institutional nutrition service control), and children's perception and practice indicator (food law perception level, sanitation perception and practice level, and nutrition balance practice). The collection of the raw data of children's food safety and nutrition safety indicators were made by the cooperation of the Korean Food and Drug Administration and the 16 local governments. The national survey was performed to collect the children's perception and practice indicator. (This research was supported by a grant (08082KFDA999‐203) from Korea Food & Drug Administration in 2010.)
Kaempferol inhibits chemokine expression and attenuates airway inflammation by suppressing STAT/JAK and NF‐kB activity in human airway epithelial cells
Authors: Gong JuHyeon , Kang Young‐Hee
Published: June 2021

Allergic asthma, a chronic inflammatory disease, is mediated by TH2 cells. Airway epithelial activation contributes to the inflammatory activities, the airway remodeling events and mucus secretion characteristics of severe asthma. Normally, the airway epithelial activation is caused by cytokines and chemokines. Kaempferol, a flavonoid which includes anti‐oxidative and anti‐tumor components, has been studied as an anti‐inflammatory agent. Thereby, in our study, we used a human airway epithelial cell (BEAS‐2B) to examine the effect of kaempferol on allergy‐connected airway inflammation. Kaempferol suppressed the lipopolysaccharide(LPS)‐induced eotaxin‐1 protein expression and IL‐8 secretion. Additionally, Kaempferol diminutioned the tumor necrosis factor‐a (TNF‐a)‐induced expression of ICAM‐1 and MCP‐1 with attenuating its monocyte‐epithelial adhesion. Furthermore, kaempferol blocked LPS‐triggered STAT/JAK TNF‐a‐induced nuclear translocation of nuclear factor‐kB (NF‐kB) Signaling respectively. Kaempferol decreases eotaxin‐1 up‐regulation by the LPS‐triggered Toll like receptors, and it was confirmed by a STAT/JAK signal. Therefore, kaemepferol is effective in ameliorating allergic and inflammatory airway diseases through its inhibitory interaction with STAT/JAK and NF‐kB signaling.
Despite High Use of Prenatal Supplements Suboptimal Vitamin D Status is Common in Pregnant Vancouver Women
Authors: Li Wangyang , Innis Sheila , Barr Susan , Whiting Susan , Green Tim
Published: June 2021

Obtaining adequate vitamin D during pregnancy is important for health of mother and child. Low circulating 25 ‐hydroxyvitamin D (25OHD) concentrations, a measure of vitamin D status have been described in pregnant women in several countries. We measured 25OHD in a multi‐ethnic group of pregnant women living in Vancouver (49°N) and explored the determinants of 25OHD. 336 pregnant women (16–47 y) between 20 and 35 weeks gestation provided a blood sample and completed questionnaires. Mean (95% CI) 25OHD was 67 (64, 69) nmol/L. Only 1% of women had a 25OHD concentration indicative of severe deficiency (<25 nmol/L). However, 24% and 65% of women were vitamin D insufficient based on cutoffs of 50 and 75 nmol/L, respectively. In multivariate analysis, mean 25OHD concentrations were 12 nmol/L higher in the Summer than Winter. Women of European (White) ethnicity had a 9–13 nmol/L higher mean 25OHD concentrations than women from other ethnic groups. Over 80% of women took vitamin D containing supplements containing ≥400 IU/d. However, 21% and 61% of these women were vitamin D insufficient based on cutoffs of 50 and 75 nmol/L, respectively. In conclusion, vitamin D insufficiency was common in this group of pregnant women. Season and ethnicity were determinants of 25OHD but the magnitude of their effect was not large. Most women took vitamin D containing supplements but this did not provide much protection against insufficiency.
Non‐canonical Wnt signaling during liver regeneration
Authors: Cusimano Antonella , Nejak‐Bowen Kari , Monga Satdarshan PS
Published: June 2021

Wnt signaling plays a central role in many processes during hepatic development and in adult liver homeostasis. Two distinct Wnt signaling pathways, the canonical and the non‐canonical pathway, have been described. Since the canonical Wnt/β‐catenin activation during liver regeneration has been previously identified and it has been demonstrated that non‐canonical Wnt pathways can antagonize the Wnt/β‐catenin pathway, we decided to study the involvement of non‐canonical Wnt during the process of liver regeneration. We used a model of 2/3rd partial hepatectomy (PH) in C57BL/6 mice, where after PH, three mice were sacrificed at 1, 2, 3, 7, 14 days and livers were harvested for paraffin embedding, protein and RNA analysis. qPCR analysis shows an increase in the expression of Wnt5a mRNA by 2‐ and 2.6‐fold after 24 and 48 hours, respectively. Fzd2 expression increases by around 2‐ and 3‐fold at 48 and 72 hours respectively, in PH samples vs sham controls. Despite modulation of Wnt5a and Fzd2, Western Blot analysis failed to show any significant differences in the activation of downstream PKC and CamKII kinases. In hepatocarcinoma cell lines Hep3B and HepG2, Wnt5a inhibits the transcriptional activity of beta‐catenin. Thus, Wnt5a may be involved in negatively regulating the Wnt/β‐catenin signaling and thus modulating hepatocyte proliferation during the liver regeneration through as yet unidentified mechanism.
Do acyl homoserine lactones (AHLs) compete with endogenous immunomodulators by acting as substrates for cyp450?
Authors: Castillo Gabriel , Haines Donovan C.
Published: June 2021

Pseudomonas aeruginosa (PA) is a major cause of fatalities in Cystic Fibrosis (CF) patients due to the virulence factors such as pyocyanin and toxins like cyanide that this organism produces. The expression of virulent genes occurs when the lipid signal acyl homoserine lactone (AHL) binds to transcription factors expressing a particular phenotype. Quorum sensing (QS) is the term given to the ability of bacteria to sense their own population density and therefore express certain phenotypes. QS is activated when AHLs reach a threshold concentration. The QSS‐regulated genes play an important role in the persistence of PA during the early infection phase. Preliminary data has shown that P450BM‐3 interacts with and can initiate inactivation of some AHLs. P450BM‐3 shares sequence homology with human P450s, including P450s that regulate immunomodulators such as leukotriene B4 (LTB4). LTB4 plays an important role in neutrophil trafficking and has been identified in large numbers in lung tissue of CF patients, and if the P450s that metabolize it also metabolize AHLs there is the potential for AHL‐mediated interference with immune regulation via this interaction. We are identifying the metabolites and which specific P450s in HLM are responsible for the hydroxylation of the AHLs. Assays were performed using human liver microsomes, NADPH and AHL but there is a need for hydroxylated AHL standards to confirm our results. Hydroxylated AHL standards where produced through an enzymatic reaction using a promiscuous mutant of P450BM‐3 in an aqueous turnover system. AHLs and their oxidation products were analyzed by GC/MS. Want to give thanks to the Robert A. Welch Foundation for the support.
PPIP5K1: A Kinase With A Cryptic Polyphosphoinositide‐Binding Domain (PBD1)
Authors: Gokhale Nikhil Arvind , Shears Stephen
Published: June 2021

The inositol pyrophosphates (InsP7, InsP8) are multifunctional signaling molecules that regulate cell and organismal energy homeostasis. Two mammalian kinases that synthesize InsP8, PPIP5K1 and PPIP5K2, were recently cloned. The kinase domain was mapped to the N‐terminal one‐third of these kinases, but unexpectedly, both enzymes were also found to contain a “phosphatase‐like” domain. In this study, we report that these “phosphatase‐like” domains are not catalytically active towards inositol phosphates. Instead, we now demonstrate using surface plasmon resonance, that these domains (we re‐designated them as polyphosphoinsoitide‐binding domains or PBDs) bind PtdIns(3,4,5)P3 with high affinity (PBD1 Kd = 96 nM; PBD2 Kd = 705 nM). PtdIns(3,4)P2 and PtdIns(4,5)P2 are 6‐fold weaker ligands and there is no significant binding of PtdIns(3,5)P2 or any of the monophosphorylated phosphoinositides. This ligand specificity is suggestive of the participation of a pleckstrin‐homology (PH) domain. Indeed, evidence from sequence alignments and site‐directed mutagenesis reveal that the PDBs consist of a partial PH domain fused to a catalytically‐inactive substrate‐binding motif from the acid‐phosphatase family. This novel domain mediates receptor‐dependent compartmentalization of PPIP5K1 at the plasma membrane where localized synthesis of InsP8 may modulate other signaling pathways.
In silico screening of chemical library for development of inhibitors of PCSK9 binding to the LDL receptor
Authors: Min Dong‐Kook , Lee Hyun‐Sook , Lee Chan Joo , Park Sahng Wook
Published: June 2021

PCSK9 is a secreted serine protease which promotes the degradation of the LDL receptor (LDLR) in liver. Inhibition of PCSK9 protein is currently being explored as a mean of lowering the plasma cholesterol level. Recently crystallographic study of PCSK9‐LDLR complex has provided the importance of the interaction between the catalytic domain of PCSK9 and the EGF‐A domain of the LDLR. In this study, a computational strategy to disrupt this interaction was used for selection of inhibitors of PCSK9 function from commercially available chemical libraries. The role of selected chemicals was evaluated in respect to the changes in expression of PCSK9 and LDLR, and the increase in the uptake of fluorescence‐labeled LDL in HepG2 cells. The preliminary data for inhibition of PCSK9‐LDLR binding in vitro were also provided. Further studies of functional evaluation in vivo to lower the plasma cholesterol level remains to be carried out for implication as a therapeutic modality to treat hypercholesterolemia. * This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2010‐0028363 and No. 2010‐0011550), and by the KHIDI‐AstraZeneca VRI Grant 2010.
The Mobile Embryo Application
Authors: Haseltine Florence Pat , Cork John , Gasser Ray , Lockett Elizabeth , Wilson Emily , Sun Ying
Published: June 2021

Embryologists worldwide use the Carnegie Collection of Embryology at the National Museum of Health and Medicine (NMHM) to define normal human embryo development. Scientists at Louisiana State University (LSU) have created 3D reconstructions and animations of the Collection. A new mobile application, called the Embryo App, incorporates information about embryos into a publicly‐available, interactive format.

The NMHM website delivers a manual of embryology that received 1450 page views in a three month period mostly from educational institutions. The Embryo App will allow for expansion of the user base and improve accessibility to existing users. Mobile devices give a tactile functionality to existing data.

The Embryo App includes movies on fertilization and in‐vitro fertilization, a pregnancy calculator, and a lab manual section. The lab manual presents photographs, 3D reconstructions, animations, reference labels, and information on the early stages (1 through 23) of embryonic development. The application links to social networks and to extended resources from the National Library of Medicine, LSU, National Museum of health and Medicine and other institutions.

The Embryo App provides a new venue for scientists, students, and the public to access and interact with the Carnegie Collection of Embryology for the first time. User evaluation will provide further information needed to improve the application and expand the outreach of NMHM.
Hydrodynamic forces regulate ECM protein expression and deposition during cardiac valve development
Authors: Biechler Stefanie , Tan Hong , Junor Lorain , Yost Michael , Potts Jay , Goodwin Richard
Published: June 2021

The primordia of atrioventicular (AV) valves are cushions that attenuate, elongate, and stiffen into fibrous tissues as they mature. It has been postulated that increasing hydrodynamic forces during development contribute to valve morphogenesis. To investigate the molecular mechanisms of flow‐generated force on valve maturation, we have utilized a novel 3D in‐vitro culture system. AV cushion explants were cultured inside a tubular collagen scaffold attached to a pulsatile pump. Estimated in‐vivo flows were applied to developing valve tissues. Data from RT‐PCR, confocal, and Western blot analyses show that flow regulates the expression and localization of ECM proteins in developing AV cushions. Further, the RhoA signaling pathway has been shown to be an important mediator of mechanical signals in endothelial cells. Our data show that RhoA mRNA levels in AV cushion explants are enhanced under flow conditioning. Additionally, compared to controls, cushion explants undergoing flow forces had increased expression of ECM proteins when treated with RhoA activator lysophosphatidic acid, while Y‐27632 Rho‐kinase inhibitor suppresses ECM protein expression. AFM studies confirm that flow and RhoA also regulate the material properties of developing valves. Our data indicate that hydrodynamic forces can drive expression and deposition of fibrous ECM proteins that are critical for proper valve morphogenesis.
Binding between IGF‐1 and IGFBP‐3 is not influenced by glucose or 2‐DG
Authors: Mireuta Matei , Hancock Mark A , Pollak Michael
Published: June 2021

A recent report details that 2‐deoxy‐D‐glucose (2‐DG), a well known inhibitor of glycolysis and a candidate antineoplastic agent, also induces insulin‐like growth factor 1 receptor (IGF‐1R) signaling through the inhibition of insulin‐like growth factor 1/ insulin‐like growth factor binding protein 3 (IGF‐1/IGFBP‐3) complex formation. The authors hypothesized that disrupted IGF‐1/IGFBP‐3 binding by 2‐DG led to increased free IGF‐1 concentrations and, consequently, activation of IGF‐1R downstream pathways. Since their report suggests unprecedented off‐target effects of 2‐DG, this has profound implications for the fields of metabolism and oncology. Using ELISA, surface plasmon resonance (SPR), and novel “intensity‐fading” mass spectrometry (MS), we now provide a detailed characterization of complex formation between IGF‐1 and IGFBP‐3. All three of these independent methods demonstrated that there was no effect of glucose or 2‐DG on the interaction between IGF‐1 and IGFBP‐3. While the mechanism implicated in 2‐DG induced increase in IGF‐1R signaling remains unresolved, our observations clearly do not support the hypothesis that 2‐DG inhibits IGF‐1/IGFBP‐3 complex formation.
DDB2, a critical mediator of reactive oxygen species
Authors: Roy Nilotpal , Kopanja Dragana , Bagchi Srilata , Raychaudhuri Pradip
Published: June 2021

Oxidative stress is an imbalance between free radical formation and anti‐oxidant defense. Reactive Oxygen Species (ROS) have been implicated in several pathological disorders. Here, we reveal a novel function of the nucleotide excision repair protein DDB2 in ROS accumulation. DDB2 deficient cells fail to accumulate ROS following DNA damage. The lack of ROS accumulation in DDB2 deficiency results from high‐level expression of the anti‐oxidant genes, in vitro and in vivo. In the absence of DDB2, the antioxidant genes MnSOD and Catalase are expressed at high levels leading to an inhibition of ROS accumulation. DDB2 represses the expression of these anti‐oxidant genes by recruiting Cul4a and Suv39h and by increasing Histone‐H3K9 tri‐methylation. Moreover, expression of DDB2 also is induced by ROS. Together, our results show that upon oxidative stress, DDB2 functions in a positive feedback loop by repressing the ROS scavenger genes, such as MnSOD and Catalase, to cause a persistent accumulation of ROS in the cell.
CINOBUFATALIN IMPAIRS FIRST TRIMESTER CYTOTROPHOBLAST FUNCTIONS VIA CELL CYCLE ARREST AND APOPTOTIC SIGNALING
Authors: Uddin Mohammad Nasir , Allen Steven R , Zawieja David C , Kuehl Thomas J
Published: June 2021

Preeclampsia is a hypertensive disorder unique to pregnancy in which marinobufagenin (MBG) is increased. We demonstrated that MBG impairs the cytotrophoblasts (CTB) functions critical for placental development. Cinobufatalin (CBT) is an analog of MBG. The aim of this study is to measure the effect of CBT on CTB cell function. The effect of CBT on CTB cell functions including proliferation, migration and invasion were investigated utilizing first trimester extravillous CTB cells. To elucidate the mechanisms by which CBT impairs CTB function, cell cycle progression and apoptotic signaling were evaluated by FACS analysis of CTBs stimulated with CBT (0.1, 1, 10 and 100 nM). The phosphorylation of p38 was evaluated by ELISA in CTB cells stimulated with CBT (0.1, 1, 10 and 100 nM). Apoptosis was evaluated by annexin‐V staining. CBT ≥1.0 nM significantly inhibited CTB cell proliferation (80%), migration (70%) and invasion (60%), whereas 0.1 nM CBT had no effect. There was a significantly higher percentage (80%) of cells in the G0/G1 phase in the cells treated with ≥1.0 nM CBT compared to basal and to 0.1 nM treated cells (55%). CBT stimulated a significant increase in dead cells by apoptotic bleb assay, increased the activation of p38 and a positive annexin‐V staining indicating the activation of apoptosis. CBT‐induced impairment of CTB cell function occurs via cell cycle arrest, p38 activation, and the activation of apoptosis.
Differential substrate selectivity and stability with different forms of protein kinase CK2
Authors: Tarrant Mary Katherine , Rho Hee‐Sool , Xie Zhi , Qian Jiang , Zhu Heng , Cole Philip A.
Published: June 2021

Protein Kinase CK2 is a highly conserved, constitutively active protein kinase with over 300 known substrates that plays a key role in cell proliferation. Others have shown that CK2 is post‐translationally modified on its C‐terminal tail with phosphorylation and O‐linked GlcNAc sites. To determine the role of these modifications on the regulation of CK2, we used protein semisynthesis techniques to generate homogenous samples of CK2α possessing the site‐specific post‐translational modifications or non‐hydrolyzable mimics of these modifications. Phosphorylation of CK2α at Thr344 enhances it cellular stability and the presence of O‐GlcNAc at Ser347 decreases the extent to which Thr344 on CK2α is phosphorylated. This enhanced cellular stability requires the phosphorylation‐dependent interactions with Pin1 protein. Inhibiting phosphorylation of CK2α or increasing the extent to which CK2α is O‐GlcNAc‐modified both result in a decrease in CK2α protein levels in cells. Kinase assays on human proteome microarray chips with the semisynthetic CK2 proteins bearing different modifications indicate that these modifications, in addition to the β regulatory subunit, lend substrate selectivity to the kinase for some of its substrates.
Effect of B‐hydoxy‐ B‐Methylbutyrate (HMB) and Resistance Training on Body Composition and Functionality in Elderly Women (65–89 yrs)
Authors: Smith Abbie E , Stout Jeffrey R , Kendall Kristina L , Fukuda David H , Moon Jordan R , Rea Marshall L , Johnson Catherine D , Cramer Joel T
Published: June 2021

HMB has been shown to slow muscle protein degradation. The effects of HMB and RT on body composition and strength in elderly women were evaluated. Ninty‐seven subjects (49 women, 48 men) consumed either a placebo (200 mg Calcium) or treatment (1.2g HMB‐200 mg Calcium) twice daily and were enrolled into a no‐training placebo group (NT); treatment (NT‐HMB), RT; or treatment plus RT (RT‐HMB), 3 d·wk−1 for 24‐weeks. Dual‐energy X‐ray absorptiometry (DXA)‐derived appendicular lean‐soft tissue was used to evaluate changes in muscle and fat mass (MM, FM).

RESULTS

At 12‐weeks there were significant increases (p<0.05) in Arms, Legs and Total Body MM (0.11–1.04 kg) for both RT groups. At 24‐weeks, RT‐HMB was significantly greater than NT and RT‐PL for upper body MM (p<0.05). Leg extension strength increased (p<0.01) for the RT and NT‐HMB groups. Handgrip and get‐up‐and go improved over time (p<0.01).

CONCLUSION

12‐weeks of HMB supplementation resulted in a possible increase in upper body lean mass and right side/dominant improvements in arm MM. At 24‐weeks, the addition of HMB to resistance training had a significant effect on increasing upper body MM. There seems to be little synergistic effect of RT with HMB on functionality. RT improved MM, but failed to elicit changes in FM. The addition of HMB, for 24‐weeks, may offer an additional advantage for increasing upper body MM in elderly women. Supported by Abbott Nutrition Grant.
Nutrition composition and antioxidant measure (ORAC) of Brazilian Camu camu fruit (Myrciaria dubia)
Authors: Wildman Robert , Jalili Thunder , Bruno Richard S
Published: June 2021

Camu camu (Myrciaria dubia) is a small bushy tree that grows in the riverside vegetation along the Amazon in Brazil and Peru and bears a reddish purple cherry‐like, sour fruit. There is growing health interest in Camu camu because of it's high levels of vitamin C, fiber and antioxidant potential, and its content of anthocyanins, vitamins and minerals. In this study, Camu camu fruit from the Amazon region of Brazil was fresh‐picked, frozen and later processed to puree and analyzed for physiochemical properties, sugars, vitamin C, β‐carotene, minerals, anthocyanins and ORAC. Results of measurements of chemical properties included: Brix (6.35), TA (3.648), pH (2.61), SG (1.024) and moisture (91%). Measurements levels (mg/100g) of key nutrients included: vitamin C (1130.0), dietary fiber (2.46), Cyanidin 3‐O‐Glucoside (3.47), Cyanidin 3‐O‐Rutinoside (7.61) and Total Anthocyanins (11.1). Antioxidant potential was assessed as Total ORAC (69.2) μmol TE/g and separable into lipophilic (1.25) and hydrophilic (67.9) ORAC μmol TE/g. Additional study is needed to better understand growing environment and seasonality on Camu camu nutrient levels as well as bioavailability and nutritional benefit to humans.
Dietary fat and carbohydrate intake during early pregnancy and risk of gestational diabetes
Authors: Ley Sylvia H , Hanley Anthony J , Retnakaran Ravi , Sermer Mathew , Zinman Bernard , O'Connor Deborah L
Published: June 2021

Dietary intake is known to influence gestational diabetes (GDM), but there is a little consensus on the optimal distribution of dietary fat and carbohydrate intake during pregnancy for GDM prevention. We aimed to investigate the impact of macronutrient intake distribution during the second trimester on the risk of GDM. Women who were with singleton pregnancies and without pre‐existing diabetes were included. Participants were asked to recall second trimester dietary intake using a validated food frequency questionnaire and in addition underwent a 3‐hour oral glucose tolerance test. Of 205 participants, 46 (22.4%) had GDM assessed at 30±2.6 (mean±SD) weeks gestation. Women who had GDM compared to those free of GDM consumed higher % intake of total fat (mean±SD: 37±5.2 v. 34±5.3 %, respectively) and lower % intake of carbohydrate (49±6.2 v. 52±6.2 %) (both p=0.01). After adjustment for age, ethnicity, family history of diabetes, prepregnancy BMI, and pregnancy weight gain, % total fat and % carbohydrate intake were individually associated with GDM (odds ratio per 5% increase 1.54 [95% CI 1.04–2.29] and 0.68 [0.49–0.93], respectively). In conclusion, dietary intakes higher in total fat and lower in carbohydrate, potential modifiable behavioral determinants, during early pregnancy were associated with increased risk for GDM later in pregnancy.
The role of neural crest progenitor number in establishing species‐specific differences in jaw size
Authors: Fish Jennifer , Schneider Richard
Published: June 2021

Objective

To test the hypothesis that differences in jaw size are dependent upon the number of neural crest progenitor cells in two morphologically distinct birds, duck and quail.

Methods

Brain regionalization and NC population were established by performing whole mount in‐situ hybridization. Neural crest progenitor number was altered by surgical manipulation.

Results

Brain regionalization markers reflect differences in the shape of the midbrain, a NC precursor domain known to contribute to the jaw, showing that duck embryos have a wider midbrain than quail embryos. This morphological difference correlates with a slight increase in the number of Sox10‐positive migrating neural crest cells at HH10, but not in the number of Pax7‐positive neural crest precursors at HH8. Surgical ablation of neural crest precursors at HH9 leads to a reduction in Sox10‐positive migrating neural crest. Depletion in migrating neural crest contributes to asymmetric development of the jaw. Jaw asymmetries decrease as development proceeds, suggesting a compensatory response of post‐migratory neural crest within the mandibular arch environment.

Conclusion

Our data indicate that a combination of factors, including neural crest cell biology and epithelial‐mesenchymal interactions, determine species‐specific differences in jaw size.

Supported by: HFSP Long‐Term Fellowship LT01061/2007‐L and NIH grant NIDCR R01 DE016402.
Appropriate Waist Circumference Cutoff Values for the Diagnosis of Metabolic Syndrome in Mexican American Adults
Authors: Jackson Robert Thaddeus , Sarafrazi Neda , Momen Bahram
Published: June 2021

Background

Metabolic syndrome (MS) increases the risk of cardiovascular disease and diabetes. The International Diabetes Federation (IDF) recently proposed new criteria for the diagnosis of the MS, which requires the presence of central obesity as measured by ethnic specific waist circumference (WC) cutoff values. Currently, no specific WC thresholds for central obesity are available in Hispanics.

Objective

To determine appropriate gender specific WC thresholds for diagnosis of central obesity in Mexican American adults and to estimate the prevalence of MS using the IDF definition with and without our modified WC in this population.

Design

Data from 3265 Mexican American adults aged 20–80 years who participated in the National Health and Nutrition Examination Survey 1999–2006 were used.

Results

ROC curve analysis suggested that yielding at least 80% sensitivity, the WC value of 90 cm in both genders was more appropriate in predicting the presence of two or more MS risk factors in this population. Based on our cutoff, there was 34% reduction in the prevalence of central obesity in women (82.5% to 54.2%). The age adjusted prevalence of MS decreased from 58.4 to 48.2%. The MS was more common among Mexican American men than women (55.8% in men versus 37.8% in women, P =0.0003).

Conclusion

Our findings provide practical guidance in the assessment and screening of central obesity and MS in Mexican Americans.
Use, perceptions and acceptability of a lipid‐based nutritional supplement for adults living with HIV – a qualitative substudy to a randomized intervention trial in Jimma, Ethiopia (ARTfood)
Authors: Olsen Mette , Tesfaye Markos , Holm Lotte
Published: June 2021

Effects of 3 months supplementation with lipid‐based nutritional supplements (LNS) in HIV patients initiating ART are investigated in a trial in Ethiopia. However, LNS does not resemble usual foods consumed in this area and little is known about it is experienced by those who receive it. The objective of this qualitative study was to investigate the use, perceptions and acceptability of the supplement among trial participants. 22 open‐ended interviews were conducted. Participants were generally happy to receive the supplement, although they found it unfamiliar and difficult to consume due to nausea in the first weeks of ART. A few left the study at this time, but most adapted to the supplement and were soon able to consume the daily dose (200g/day). Some described worries of HIV disclosure due to lack of privacy for taking LNS. Participants were generally very motivated to use it and had high expectations to its effects. Weight gain was largely attributed to LNS and it was described as a mean to rebuild and recover the body. Despite the large quantity, LNS was mainly seen as a snack and eaten separately from ordinary meal situations. Some left their normal food share for family members but the majority used it as an additional food with little influence on other food intake. LNS was described as a “special” or “medical” food, which meant that many social and religious conventions that normally pertain to food did not apply to it. Therefore, in this setting, fasting and expectations of sharing were not problematic for the acceptability of LNS. Trial funded by USDEC
Burden of Sickle Cell Disease and Alpha‐Thalassemia among Young Children in Western Kenya
Authors: Suchdev Parminder Singh , Ruth Laird , Williams Thomas N.
Published: June 2021

Background

Although hemoglobinopathies such as sickle cell hemoglobin and alpha‐thalassemia are common in Africa, there are limited data on their prevalence or their contribution towards childhood anemia.

Objective

To determine the prevalence of hemoglobinopathies in preschool children in western Kenya and understand their contributions to anemia.

Methods

We conducted a cross‐sectional survey of 860 children aged 6–35 months randomly selected from 60 villages in western Kenya. Hemoglobin (Hb), ferritin, transferrin receptor, malaria, C‐reactive protein (CRP), retinol binding protein (RBP) and hemoglobin genotype were measured.

Results

Of 828 children with sufficient blood samples, 430 (51.9%) were negative for the ‐3.7kb alpha‐thalassaemia deletion while 319 (38.5%) were heterozygous, and 79 (9.5%) were homozygous. Sickle cell trait and disease were found in 134 (17.2%) and 14 (1.8%) of children, respectively. After excluding 607 children with malaria parasitemia, inflammation (CRP>10 mg/L), iron deficiency (iron stores<0), or vitamin A deficiency (RBP<0.7 mmol/L), there remained a significant difference in the prevalence of anemia among those without alpha‐thalassemia (36.6%), heterozygotes (44.3%), and homozygotes (67.9%, p=0.01).

Conclusions

Hemoglobinopathies are prevalent among pre‐school children in western Kenya and are an important contributor to anemia.
Effects of endothelin antagonism on VEGF and NO levels in penile tissues in type 1 diabetic rat model
Authors: Jesmin Subrina , Mowa Chishimba , Zaedi Sohel , Sultana Sayeeda Nusrat , Yamaguchi Naoto
Published: June 2021

Erectile dysfunction (ED) affects about 50% of males with diabetes, possibly due to the vascular and neuropathic complications. The pathogenic significance of Vascular endothelial growth factor (VEGF) in different diabetic complications have been extensively documented and we have previously reported that its (VEGF) signaling is greatly diminished in the penis a type II diabetic rat model at the insulin‐resistant stage. In the present study, we used a rat model that was treated for three weeks with streptozotocin (STZ), a chemical that induces diabetes, in order to assess the expression patterns of VEGF and the NO system in penile tissue and the effects of endothelin antagonism on these changes. Male Sprague‐Dawley rats (weight, 450±26 g) were administered citrate saline vehicle or STZ (65 mg/kg IP). Diabetes was confirmed by hyperglycemia and after 1 week of diabetes, animals were either treated with endothelin‐A (ET‐A) receptor antagonist (TA‐0201, 1 mg/kg) or saline for 2 weeks by osmotic mini pump and then sacrificed. Levels of glucose levels in DM rats were found to increase significantly (405±103 mg/dL) compared to non‐DM rats (120±8 mg/dL) and ET‐1 levels in DM penis was found to be higher by 20%. A 30% decrease in VEGF levels was observed in penile tissue of DM rats and ET‐A antagonist did not attenuate the observed decrease in VEGF levels. Lastly, penile levels of NO and eNOS decreased in DM rats, but were almost restored back to normal by ET‐A receptor antagonist. We conclude that ET antagonism is not effective in restoring the down‐regulated levels of VEGF, but is effective in reversing the decreased levels of NO and eNOS in DM penis.
Role of diabetes induced arginase in coronary vascular proliferation, enhanced collagen formation and fibrosis
Authors: Bhatta Anil , Toque Haroldo A Flores , Yao Lin , Alkilany Alaaldin M , Romero Maritza J , Caldwell Ruth B , Caldwell R. William
Published: June 2021

Excess arginase activity can contribute to vascular dysfunction by competing with NOS for their common substrate L‐arginine and decreasing NO production. Overactive arginase can also alter vascular function by activating the ornithine decarboxylase (ODC) and ornithine aminotransferase (OAT) pathways. This can increase cell growth and fibrosis via increased synthesis of polyamines and proline/collagen, respectively. We hypothesize that diabetes/high glucose (HG) alter coronary artery structure and enhance collagen formation/fibrosis by activating the arginase, ODC and OAT pathways. Coronary arteries of 8‐week diabetic WT mice showed vascular wall thickening and perivascular fibrosis, suggesting increased activity of ODC and OAT. Coronary artery structure in arginase I knockout diabetic mice (AI+/−) was comparable with non‐diabetic controls. Aortas of diabetic WT mice also exhibited a marked reduction in maximum endothelium‐dependent relaxation to acetylcholine compared to WT mice. This impairment was significantly reduced by treatment with an arginase inhibitor. Treatment of cultured cells with HG (25mM, 48hr) or Ang II (1.0uM, 48hr) resulted in increases in arginase activity, ODC expression and cell proliferation, suggesting increased polyamine formation. In conclusion, our data suggest important roles of arginase, ODC and OAT in diabetes‐induced vascular dysfunction and fibrosis.
Selective modulation of the endocannabinoid system for targeted protection in kainic acid models of excitotoxicity
Authors: Naidoo Vinogran , Karanian David A , Nikas Spyros P , Graves Emily E , Wood JodiAnne T , Makriyannis Alexandros , Bahr Ben A
Published: June 2021

The endocannabinoids anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG) have been implicated in neuroprotective responses against excitotoxic events linked to seizure activity and associated neurodegeneration. Related to such responses to injury, excitotoxic kainic acid (KA) injections increase AEA levels in the brain. To study the modulation of this response in vitro and in vivo, we utilized new‐generation compounds (AM5206 and AM6702) that selectively inhibit the AEA deactivating enzyme fatty acid amide hydrolase (FAAH), as well as a dual inhibitor (AM6701) that blocks FAAH and the 2‐AG deactivating enzyme monoacylglycerol lipase (MAGL). AM5206 protected against the KA‐induced degenerative cascade in hippocampal slices assessed 24 h post‐insult. Cultured slice data also suggest AM6701 elicits more protection than AM6702 by ameliorating cytoskeletal breakdown and declines in synaptic markers and neuronal integrity. In vivo, KA administration induced seizures and the same neurodegenerative events exhibited in vitro. Protection by AM5206 and AM6701 was evident with respect to cytoskeletal damage, pre‐ and postsynaptic markers, seizure scores, and behavioral deficits. Our study has identified and characterized new‐generation inhibitors of endocannabinoid‐degrading enzymes to enhance cannabinergic signaling, and in turn prevent excitotoxic progression that cause brain damage.