bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell Surface Localization and Shedding of the Candidate Tumor Suppressor Ligand Ecrg4 after Neutrophil Activation and Polarization
Authors: Lopez Nicole , Dang Xitong , Krzyzaniak Michael , Eliceiri Brian , Baird Raul Coimbra Andrew
Published: June 2021

We identified fresh human leukocytes as an abundant source of the candidate epithelial tumor suppressor gene, Ecrg4; an epigenetically regulated gene that, unlike other tumor suppressor genes, encodes an orphan secreted ligand‐like protein. In cultured human cell lines, Ecrg4 gene expression was low, the Ecrg4‐ encoded protein undetectable and Ecrg4 promoter hypermethylation was high (45–90%). Low gene expression was also reversible by incubation with the methylation inhibitor 5‐Aza‐ Cytidine. In contrast, Ecrg4 gene expression in fresh normal human peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) was 600–800 times higher than cultured cells, the protein was readily detected in cell lysates and Ecrg4 promoter hyper‐methylation in normal leukocytes was low (<3%). Immunoblotting, cell surface biotinylation, immunofluorescent staining and cell flow analyses also established that the Ecrg4‐encoded protein was not constitutively secreted but instead exists as an extracellular, membrane‐anchored protein on the surface leukocytes. Its presence on the surface however is dynamic and upon leukocyte activation by 5 min incubations with fMLP, cell surface Ecrg4 protein is shed in concordance with fMLP‐activation of neutrophils and polarization. In light of these findings, we propose that the pathological sequelae of losing Ecrg4 expression in cancer may reflect a more global physiological response that links Ecrg4 to the biology of leukocytes in cancer surveillance, innate immunity, injury and inflammation.
Secondary lymphoid organs and CCR7 are dispensable for intestinal Th17 and Foxp3+ Treg cell differentiation
Authors: Geem Duke , Medina Oscar , Kim Wooki , Huang Clifton , Newberry Rodney , Denning Timothy Luke
Published: June 2021

The intestinal immune system maintains homeostasis by promoting tolerance to the microbiota and food antigens while mounting inflammatory responses towards pathogens. Effector and Foxp3+ Treg cells are enriched in the intestinal lamina propria (LP) and are believed to be generated in the mesenteric lymph nodes (mLN) upon instruction by migrating CCR7+ LP dendritic cells. Herein, we demonstrate using multi‐color flow cytometry normal frequencies and cell numbers of Th17 cells and functional Foxp3+ Treg cells in the intestinal LP of mice deficient in lymphotoxin (LT)α, LTβR, and CCR7. In the absence of secondary lymphoid organs due to LTα deficiency, CD4+ T cell differentiation was not simply shifted to the spleen since splenectomized LTα‐deficient mice exhibited no defects in intestinal Th17 or Foxp3+ Treg cells. Using an OT‐II adoptive transfer system, naïve OT‐II CD4+ T cells differentiated into induced Foxp3+ Treg cells in the intestine in response to the feeding of ovalbumin to LTα‐deficient mice. Collectively, these data suggest that secondary lymphoid organs including mLN are not required for the differentiation of resident intestinal Th17 and Foxp3+ Treg cells and implicate the intestinal LP as a potentially important site for this process.

Supported by NIH grants (AA01787001, AI083554), Career Development Award from CCFA, and Emory Egleston Children's Research Center seed grant to T.L.D.
Absence of microRNA‐155 protects against pressure overload‐induced cardiac inflammation and failure
Authors: Schroen Blanche , Corsten Maarten , Janssen Ben J , Creemers Esther E , Pinto Yigal M , Zacchigna Serena , Giacca Mauro , vigorito elena , Thum Thomas , carmeliet peter , Mayr Manuel , de Windt Leon , Lutgens Esther , de Winther Menno , Papageorgiou Anna , Heymans Stephane
Published: June 2021

Cardiac hypertrophy, accompanied by progressive inflammation, and consequent heart failure (HF) continue to burden Western society. We show that miR‐155, a microRNA expressed by cardiac macrophages, stimulates the secretion of pro‐hypertrophic and ‐ inflammatory factors by macrophages and thereby causes adverse inflammation and HF.

We subjected miR‐155 knockout (KO), wild type (WT) and antagomiR‐treated mice to pressure overload by angiotensin II or transverse aortic constriction to induce cardiac hypertrophy, inflammation and failure. Absence of miR‐155 inhibited the cardiac hypertrophic response and hampered cardiac macrophage activity. Bone marrow transplantation with miR‐155 KO and WT mice confirmed that miR‐155 in the macrophage mediates cardiac hypertrophy. It does so by repressing its direct target Suppressor of Cytokine Signalling‐1, leading to increased cytokine secretion and STAT3 activity, both implicated in cardiac inflammation and hypertrophy.

These findings demonstrate the causative relation between inflammatory signalling and HF, and implicate microRNA‐155 as a therapeutic target in heart failure.
The proton pump inhibition removes alcoholic fatty liver disease via inactivation of TLR signaling pathway
Authors: Matsumoto Hiroshi , Okazaki Shunichiro , Tateda Kenji , Mizuo Keisuke , Katada Ryuichi , Ishizaka Atsushi , Watanabe Satoshi
Published: June 2021

Pathogenesis of alcoholic fatty liver disease has never been established. It has been that TLR‐signaling pathway plays an important role in the development. What primes TLR‐signaling pathway and any prevention remains unclear. The proton pump exists in endosome in macrophage. Endosome includes TLR4, TLR7 and TLR9, which may contribute to innate immune response in macrophage. We hypothesized that inhibition of proton pump reduces alcoholic fatty liver disease. To clarify the hypothesis, we evaluated fatty liver injury in alcohol‐fed rats after treatment with a proton pump inhibitor. Male Wistar rats were fed with Lieber‐DeCarli alcohol liquid diet for 4 weeks. Lansoprazol, a proton pump inhibitor, was treated to alcohol liquid diet‐fed rats. Immunohistochemical staining for TLR7 and TLR9 was performed in formalin‐fixed, paraffin‐embedded liver sections. ER stress markers were analyzed by quantitative real‐time PCR. Alcohol feeding caused expression of TLR7 and TLR9 and accumulation of ER stress. Inhibition of proton pump results in reduction of fatty liver change, especially lipid droplets in hepatocytes and no staining for TLR7 and TLR9. However, accumulation of ER stress was not changed by inhibition of proton pump. Therefore, chronic alcohol consumption causes developing fatty liver disease via TLR7 and TLR9, which expression can be reduced by inhibition of proton pump.
The Virtual Human Embryo Project: A Resource for the Study of Human Embryology
Authors: Cork R. John , Gasser Raymond F.
Published: June 2021

The Virtual Human Embryo Project (VHE) began in 2000 with the goal of producing image databases of serially sectioned human embryos. Each database would include a set of labeled sections, a 3D reconstruction of the embryo's surface morphology and some basic information about the stage of development. The sections were to be aligned ready for further 3D reconstructions and could also be used to produce a variety of animations. The specimens used for the image databases were selected from the best representative examples in the Carnegie Collection at the Human Developmental Anatomy Center (HDAC) in Washington DC. All of the image capture was done at HDAC using an automated stage, and the images sent to LSUHSC for ‘tiling’, restoration, and alignment. After establishing ‘proof of concept’, funding for the project was provided by the National Institute for Child Health and Human Development and the databases were made available on a set of DVDs and CD‐ROMs. Additional funding was provided by the National Library of Medicine to produce more detailed 3D reconstructions, flythrough animations and to make the image databases available on the Web. As of May 2011 we have completed 27 databases, at least one for each of the 23 Carnegie stages. The databases are available on disk or accessible on the website http://virtualhumanembryo.lsuhsc.edu. Funded by NIH grants; HD37811 to R.F. Gasser and LM007591 to R.J. Cork
A Designer Artificial Transcription Factor Stably Reprograms Cancer Cells by Targeted DNA Methylation
Authors: Rivenbark Ashley G , Stolzenburg Sabine , Strahl Brian D , Blancafort Pilar
Published: June 2021

The ability to stably alter gene expression states via epigenetic reprogramming hold significant implications for controlling breast cancer and other cancers. Herein, we describe a novel approach using artificial transcription factors (ATFs) to epigenetically target and stably down‐regulate genes that are aberrantly expressed in breast cancer. Our objective was to develop ATFs that contain zinc finger proteins coupled with DNMT3a to target and epigenetically repress Maspin (tumor suppressor) and SOX2 (oncogene). Upon ATF transduction in SUM159 cells that express Maspin at a moderate level, we significantly down‐regulate Maspin expression levels and repression was directly associated with ATF‐mediated DNA methylation adjacent to the ATF binding site. ATF‐transduced cells formed colonies in soft agar and selected clonal populations expanded from these colonies displayed persistent, heritable silencing of Maspin over many cell generations due to promoter methylation. Upon ATF transduction in MCF7 cells that overexpress SOX2, we observed a significant down‐regulation of SOX2 followed by cell arrest and death. These observations combine to strongly suggest that this technology will enable directed DNA methylation that can be utilized to modify the epigenetic status of any target gene in any cancer cell type. A.G.R. supported by ACS Postdoctoral Fellowship 116066‐PF‐08‐166‐01‐GMC.
Detection and quantification of 7,12‐dimethylbenzanthracene (DMBA) in the liver and adipose tissue by HPLC
Authors: Jesus Patricia , Gonçalves Nuno , Costa Joana , Pereira Felipe , Pereira Mariette , Cabrita Silvério
Published: June 2021

DMBA is an environmental pollutant present in cigarette smoke, automobile exhaust, grilled food, woodsmoke, etc[1]. It is the one of the most potent carcinogenic polycyclic aromatic hydrocarbons, can induce in experimental animals not only skin tumors, but also lung and mammary cancers[2]. The objective of this study is the morphological and molecular evaluation in the experimental administration of 7,12‐dimetilbenzantraceno (DMBA). These evaluations were performed in liver and adipose tissue because the toxic is metabolized in the liver and appear to accumulate in adipose tissue.

Ten Wistar male rats, 8 weeks old were submitted to a quarantine period of one week, and then distributed by two groups: the test group, submitted to the oral administration of DMBA 20mg/kg/day, three times a week (Monday, Wednesday and Friday), for four weeks and the control group, kept on the standard conditions.

The results of this study, lead us to think that DMBA can become stored on the adipose tissue, with a correlation with the concentration on the liver.
Global Gene Expression Changes In Regenerating Mouse Liver Following Concurrent Inhibition of MET & EGFR
Authors: PARANJPE SHIRISH , Bowen William , Bhave Vishakha , Luo Jianhua , Orr Ann , Michalopoulos George
Published: June 2021

The HGF receptor MET and the EGF receptor (EGFR) are the only two mitogenic receptor‐tyrosine kinases for hepatocytes. We now report the results on liver regeneration in mouse following concurrent inhibition of kinase activity of MET & EGFR by using Gefitinib and JNJ 38877605 respectively. Mice were administered two doses of Gefitinib (300 mg/kg) and JNJ 38877605 (100 mg/kg) by oral gavages. Combined inactivation of both receptors coupled with partial hepatectomy leads to massive hepatocyte death and liver failure. Western blot analyses revealed significant inhibition of both phosphoMet and phosphoEGFR. Analyses of proliferative indices indicated significant suppression of mitoses and Ki67 staining in treated animals compared to vehicle treated controls. Global changes in gene expression, particularly down regulation of genes associated with cell cycle and prosurvival pathways and up regulation of proapoptotic genes was apparent by gene array analyses. Array data was confirmed by Real time RTPCR analyses of genes associated with the apoptosis pathway. TUNEL assays also revealed significant staining in treated animals compared to controls. We are currently investigating the mechanisms and the pathways activated by combined inhibition of the two receptors that lead to hepatocyte death and liver failure.
Enabling Xenopus oocytes and embryos to perform RNAi
Authors: Sheets Michael , Lund Elsebet , Imboden Susanne Blaser , Dahlberg James
Published: June 2021

Although Xenopus laevis is a powerful model organism that has provided critical mechanistic insights into vertebrate development, cell biology and neural biology its utility has been limited by a lack of genetic analysis and gene manipulation. Other organisms that are difficult to manipulate genetically have often been studied by the use of RNAi, the inactivation of specific genes through the use of small interfering RNAs (siRNAs) that target the mRNAs of these genes for degradation. However, RNAi does not work in Xenopus oocytes or early embryos, making it impossible to use siRNAs in the analysis of early stages of Xenopus development. Thus new methods or tools that would support the study of these events are greatly needed.

Recently, we discovered that Xenopus oocytes and early embryos lack functional Ago2, the nuclease containing protein that is guided to targeted mRNAs by siRNAs, which would explain why these cells are unable to carry out RNAi. Fortunately, we have also found that exogenous Ago2 generated from injected in vitro synthesized mRNA overcomes this deficiency. Thus we can now perform RNAi in Xenopus oocytes and early embryos, potentially making them amenable to genetic analysis through inactivation of specific gene products.
A new class of intron‐derived long noncoding RNAs
Authors: Carmichael Gordon , Yang Li , Chen Ling-Ling
Published: June 2021

RNAs can be physically classified into poly(A)+ or poly(A)− according to the presence or absence of a poly(A) tail at their 3′ ends. Current deep sequencing approaches largely depend on the enrichment of transcripts with a poly(A) tail, and therefore offer little insight into the nature and expression of transcripts that lack poly(A) tails. We have used deep sequencing to explore the repertoire of both poly(A)+ and poly(A)− RNAs from HeLa cells and H9 human embryonic stem cells (hESCs). Using stringent criteria, we found that while the majority of mRNAs are poly(A)+, a significant portion of mRNAs are either poly(A)− or bimorphic, being found in both the poly(A)+ and poly(A)− populations. In addition to the demonstration that many mRNAs may not contain classical long poly(A) tails, we also identified a number of new long noncoding RNAs (lncRNAs) that are derived from excised introns and accumulate to high levels in cells. Several especially striking examples of this class of noncoding RNAs were discovered in hESCs. These lncRNAs (named sno‐lncRNAs) are expressed from introns that contain two snoRNA genes. They are uncapped and non‐polyadenylated and appear to depend on snoRNAs at both ends for proper processing. The most abundant sno‐lncRNAs are associated with the human disease Prader‐Willi Syndrome and are highly expressed in brain, ovary, and prostate as well as in cell lines derived from these tissues. In addition, they are nuclear retained but do not accumulate in nucleoli or colocalize with a marker for Cajal bodies. We will discuss current work on the characterization and processing mechanism of these snolncRNAs.
Regulation of Form and Function in the Nervous System of Honey Bees
Authors: Fahrbach Susan E
Published: June 2021

The honey bee, Apis mellifera, has long been a focus of researchers interested in pollination, behavioral ecology, and evolution of sociality. A distinct academic tradition rooted in the work of ethologist Karl von Frisch used the honey bee to explore learning, memory, and social communication. Humans have engaged in beekeeping for thousands of years. The separate perspectives of ecology, ethology, and apiculture provide a sturdy foundation for contemporary honey bee neurobiology. The first comprehensive study of the honey bee brain in English was published in 1896 by F.C. Kenyon. Studies in the early 1990s revealed that the brains of forager honey bees can be distinguished from those of nestmates working inside the hive by volume of neuropil associated with the protocerebral mushroom bodies. These neuropils are organized around the axons and dendrites of neurons called Kenyon cells. Subsequent studies of mushroom body plasticity documented that foraging experience drives growth of the mushroom body neuropil by promoting branching of Kenyon cell dendrites. Experience‐dependent changes in volume of mushroom body neuropils of adults have been documented in the brains of other insects, including but not limited to other social hymenopterans. The persisting challenge is to relate this striking example of structural plasticity in the adult brain to functional changes in sensory integration and behavior.
Specific N‐glycans on SynCAM Ig proteins regulate synaptic adhesion and synapse development
Authors: Biederer Thomas
Published: June 2021

Neurons communicate at specialized cell junctions called synapses. The protein complexes that span the synaptic cleft not only hold synapses together but also guide synapse development. SynCAMs (Synaptic Cell Adhesion Molecules) are a family of four homo‐and heterophilic immunoglobulin (Ig) proteins that contribute to these trans‐synaptic interactions. SynCAM 1 first participates in axo‐dendritic contacts of pre‐ and postsynaptic neurons and SynCAM proteins then drive the formation of excitatory synapses. Interestingly, the site‐specific N‐glycosylation of SynCAMs is a novel mechanism to regulate synapse development. Our mass‐spectrometric, crystallographic, and functional analyses of SynCAM 1 and 2 demonstrate that they carry N‐glycans adjacent to and within the first Ig domain that provides their extracellular binding interface. The glycosylation of these two SynCAM family members serves different roles. While N‐glycans within the Ig1 binding interface of SynCAM 2 reduce its binding, glycosylation at the SynCAM 1 Ig1 domain promotes its adhesion. Consequently, the ability to N‐glycosylate SynCAM 1 increases its trans‐synaptic interactions and synapse‐inducing activity. Together, N‐glycans modulate the adhesive interactions and synapse‐organizing functions of SynCAMs. Our findings support the notion that glycosylation plays important roles in synaptic surface interactions.
New Frontiers: Science and Science Education in “Emerging” Countries
Authors: Shenolikar Shirish
Published: June 2021

Singapore, a city‐state with limited natural resources, has invested heavily in the development of its human capital with the goal of building a sustainable knowledge‐based economy. This has required a highly educated workforce that acquires and applies knowledge to generate innovative technology and products for the 21st century. In addition to the outstanding undergraduate education available at local universities, Singapore is also blessed with a very high standard of healthcare, making it a magnet for medical tourism in South‐East Asia. In 2005, the collaboration between National University of Singapore (NUS) and Duke University led to the formation of Duke‐NUS Graduate Medical School, Singapore, whose principal focus is to train physician‐scientists that can aid and attract the growing R&D efforts of major international pharmaceutical companies in Asia. In delivering on its research and education goals, Duke‐NUS has adopted a novel Team‐LEAD curriculum that places significant emphasis on students to learn and teach each other as well as provides a forum for discussion and debate not often seen in medical schools in Asia. One goal of this education system is to encourage innovation and entrepreneurship while exploring the full potential or educational capabilities of our students. The excitement of embarking on a new educational venture in Asia and the challenges of training clinician scientists for the new information age will be discussed.
Prediagnostic Serum Carotenoid Levels and the Risk of Non‐ Hodgkin Lymphoma: The Multiethnic Cohort
Authors: Maskarinec Gertraud , Ollberding Nicholas J , Conroy Shannon M , Morimoto Yukiko , Franke Adrian A , Cooney Robert V , Wilkens Lynne W , Le Marchand Loic , Goodman Marc T , Hernandez Brenda Y , Henderson Brian E , Kolonel Laurence N
Published: June 2021

A diet rich in fruits and vegetables has been associated with a lower risk of non‐Hodgkin lymphoma (NHL) in several reports. The objective of this analysis was to examine prospectively whether circulating levels of several carotenoids found mainly in these foods are consistent with this association. We conducted a nested case‐control analysis within the Multiethnic Cohort for 271 NHL cases and 538 controls matched on sex, ethnicity, location (Hawaii or Los Angeles), age at blood draw, date and time of blood draw, and hours fasting prior to blood draw. Plasma carotenoid levels were obtained by HPLC/photodiode‐array detection. Conditional logistic regression was used to calculate odds ratios (OR) for the risk of NHL according to tertiles of serum carotenoids. Total carotenoids (OR=0.66 [0.46–0.96] T3 vs. T1; ptrend=0.05), lycopenes (OR=0.54 [0.38–0.78] T3 vs. T1; ptrend=0.001), and α‐cryptoxanthin (OR=0.53 [0.36–0.78] T3 vs. T1; ptrend=0.002) were associated with a lower risk of NHL. Risk estimates remained unchanged with adjustment for NHL risk factors and were similar in analyses stratified by sex, ethnicity, and NHL subtype. Other carotenoids, including α‐ or β‐carotene, lutein, and zeaxanthin showed no association with risk. These data provide support for a protective role of carotenoid‐rich fruits and vegetables in the etiology of NHL.
Mammalian selenocysteine tRNA Um34 methylase and its role in selenoprotein synthesis
Authors: Chen Fang , Hofmann Peter , Carlson Bradley A , Tobe Ryuta , Schomburg Lutz , Gladyshev Vadim N , Schweizer Ulrich , Hatfield Dolph L
Published: June 2021

Selenocysteine (Sec) tRNA plays a key role in recoding the UGA stop codon to insert the 21st amino acid, Sec, into selenoproteins (SPs). The mammalian Sec tRNA population consists of two isoforms that differ by a single methyl group, 2’‐O‐methylribose, at the nucleotide 34 wobble position in the anticodon (designated Um34). Um34 synthesis is a highly specialized event in mammalian Sec tRNA maturation and is involved in the synthesis of a subgroup of SPs implicated in stress‐related phenomena. We used a comparative genomic approach and knockdown/knock‐in techniques to uncover a purported Um34 methylase. Knockdown of Um34 methylase in NIH3T3 cells resulted in decreased glutathione peroxidase 1 (GPx1, a stress‐related SP) expression. Over‐expression of this methylase led to an increase in GPx1 synthesis. Um34 methylase synthesis is regulated by selenium status. The data suggest that Sec tRNA Um34 methylation is carried out by the purported methylase. Further investigation of this methylase may provide new avenues to modulate SP synthesis, and further assess its role in disease including certain cancers. Funding: Intramural Research Program, NIH, NCI, CCR and DFG grants to U.S. and L.S.
Habitual calcium intake and vitamin D status during adulthood through estrogen deficiency have few interactions on calcium kinetics and bone
Authors: Park Clara , Lee WangHee , Allen Matthew , Fleet James , McCabe George , Weaver Connie
Published: June 2021

Eating patterns do not change as rapidly as the physiological changes that accompany the menopause. As such, habitual nutrition status may strongly affect post menopausal bone health in the general population. To test how dietary calcium (Ca) and vitamin D (VD) interact to influence bone during the menopause, we studied 70 female Sprague Dawley rats from young adulthood through ovariectomy (OVX)‐induced estrogen deficiency. Weanling rats were housed in a UV‐free environment and fed an AIN93G diet with 0.4% Ca and 100 IU VD/kg diet for 5 weeks. At 8 weeks of age, rats were randomized to AIN93M diets containing 0.2 or 1.0% Ca and 50, 100, or 1000 IU VD/kg diet. OVX was performed at 12 weeks of age. At 24–28 weeks of age, Ca kinetics was performed with a 45Ca tracer (oral Ca dose: 15 mg) up to 48 hours. Kinetics was modeled using WinSAAM software. A Ca and VD interaction was seen in the soft tissue compartment, but each nutrient independently increased endogenous Ca secretion. Bone formation was not affected by either nutrient. However, rats on the 1% Ca diet had lower fractional Ca absorption, higher net Ca absorption and higher bone balance due to reduced bone resorption, regardless of VD intake. Habitual Ca intake and VD status during adulthood throughout estrogen deficiency have few interactions on Ca kinetics and bone. Rather, Ca intake may be more influential to benefit bone than VD status at levels relevant to the general population.
Improving vitamin D status in home‐bound elders
Authors: Houston Denise K , Tooze Janet A , Demons Jamehl , Davis Brooke , Shertzer-Skinner Rachel , Kearsley Linda , Gottlieb Richard , Williamson Jeff
Published: June 2021

Home‐bound older adults are at particularly high risk of having vitamin D insufficiency. We conducted a 5‐month randomized, controlled pilot study to assess the feasibility of delivering vitamin D supplements to home‐bound elders receiving Meals on Wheels (MOW) in Forsyth Co, NC, and the effectiveness of the vitamin D supplements to improve 25‐hydroxyvitamin D (25(OH)D) concentrations and reduce falls (n=68; mean age, 77.8 yrs; 72% women; 75% black). 25(OH)D was measured at baseline and follow‐up and falls assessed by monthly fall calendars. Participants received 100,000 IU vitamin D3 (n=38) or placebo (n=30) once a month along with their MOW meal. 25(OH)D concentrations (mean±SD) at baseline were 22.5±12.2 and 18.9±10.6 ng/mL in the intervention and control group, respectively (p=0.22). 25(OH)D concentrations improved significantly in the intervention group compared to the control group (LS means±SE: +20.4±1.8 vs. −2.2±2.1 ng/mL adjusted for age, gender, race, randomization group, and baseline 25(OH)D, p<0.0001). There were also significantly fewer falls in the intervention group compared to the control group (LS means±SE: 0.3±0.3 vs. 1.1±0.3, p=0.05). In summary, providing supplemental vitamin D through the MOW program is feasible and effective in improving 25(OH)D concentrations and reducing falls. Supported by the Wake Forest School of Medicine Translational Science Institute.
Formative research to inform the development of a community‐based intervention for chronic disease prevention in Guatemalan school‐age children
Authors: Letona Paola , Gittelsohn Joel , Ramirez-Zea Manuel , Caballero Benjamin
Published: June 2021

Objective

Chronic disease risk factors have increased in children, even in developing countries. Preventive interventions that address modifiable risk factors are needed. Formative research was conducted to assess perceptions about health concerns for children; factors that influence their diet, physical activity and tobacco use; and community resources available for the promotion of healthy lifestyles.

Methods

A convenience sample of 6 schools located in 3 low‐income urban communities of Guatemala City was studied. At each school, focus group discussions, semi‐structured interviews, home visits, and direct observations of the surroundings were conducted, with the participation of children (10–12 y old), teachers, parents, school administrators, food vendors and community leaders.

Results

All groups expressed similar concerns about modifiable risk factors in children, including high violence rates, food advertising, mother's employment, family customs, bullying and negative emotions that seem to increase unhealthy behaviors. Adults were more concerned with tobacco and alcohol use compared to unhealthy diet and physical inactivity. Government programs and religious groups were identified as community resources.

Conclusions

These findings were used to develop the first community‐based intervention for chronic disease prevention in Guatemala.

Grant Funding Source : NHLBI ‐ HHSN 268200900028C
Maternal fat gain modulates insulin response among overweight/obese women
Authors: De Haene Jessica , Murphy Elizabeth , Stotland Naomi , Barros Viviana Ruiz , Hernandez Gabriela , Rodriguez Marcela Perez , Castaneda Diana , Havel Peter J , King Janet C
Published: June 2021

Gestational weight gain recommendations for varying pre‐pregnancy body mass indexes (PPBMI) are based on healthy pregnancy outcomes. However, among overweight/obese women, the composition of weight gain might be a better indicator of underlying metabolic alterations (i.e., insulin resistance (IR) and/or inflammatory processes). We compared indicators of IR and inflammation between overweight/obese pregnant women, divided into 2 groups: 1) Low fat gain (LFG) ≤0.5 kg and 2) High fat gain (HFG) >0.5 kg, @ 20–34wk gestation. Body composition was estimated using body density. Women were normoglycemic. Weight gain was 3.9±3.0kg in the LFG group (n=24) and 6.9±2.9 kg in the HFG group (n=30); p<0.001. The LFG group lost − 1.2±1.5 kg of fat mass and the HFG group gained 2.9±1.8kg. Glucose & insulin areas under the curve (AUC) were calculated from a 100g OGTT completed at 20 and 34wk gestation. Fasting leptin, cortisol and CRP were also determined. Birth outcomes were obtained from medical records. Increases in leptin, and insulin AUC were significantly greater in the HFG group vs the LFG after controlling for PPBMI: Leptin (−1.1±1.8 vs 1.9±1.3 ng/mL; p<0.017); insulin AUC (51.9±25.6 vs 120.2±30.0uU/hr/mL; p<0.048). No differences were found between changes in CRP, cortisol or glucose AUC between groups. Newborn weight and gestational age at birth were not different between groups. In conclusion, lower fat gain among overweight/obese women during the last half of pregnancy may improve maternal insulin sensitivity without affecting fetal growth. Funded by NIH grant # R01HD46741
The most frequently reported foods and beverages differ by age among participants of NHANES 1999–2008
Authors: Eicher-Miller Heather A. , Boushey Carol J.
Published: June 2021

Technology assisted methods of dietary assessment are evolving. Limited screen space of mobile devices necessitates abbreviated food lists for rapid identification. Thus, knowledge of frequently reported foods and beverages is critical for tailored search tools. National Health and Nutrition Examination Survey (NHANES) analysis identifying top contributors to energy does not inform the frequency of such items as diet soda. The purpose of this study was to determine the most frequently reported foods or beverages for individuals aged 11–14y, 15–21y, and 22–65y. Data were from the NHANES 1999–2008, a nationally representative cross‐sectional survey. Diet was assessed by 24‐hour dietary recall using USDA's Food and Nutrient Database for Dietary Studies. Adults differed from adolescents by variety of reported foods. Only 1.6% of all foods were reported ≥100 times among 11–14y group compared with 2.2% among the 15–21y and 5.9% among adults. Candies were itemized 4 times among the top 100 reported foods for adolescents and only once among adults. Soft drinks captured 1st and 2nd most frequently reported foods for the 15–21y group and appeared twice in the 11–14y top 10 reported foods but only once in the adult list. Beverages featured heavily in all three groups’ top 10 list of foods, capturing ≥5 places. Age is an important characteristic to consider for developing a concise food list to describe the US diet. NIH & NIDDK
Gestational Weight Gain Trends among WIC Participants in Los Angeles County
Authors: Koleilat Maria , Whaley Shannon , Gee Denise
Published: June 2021

Among the gaps identified in the 2009 revision of the Institute of Medicine (IOM) recommendations for gestational weight gain (GWG) was the paucity of GWG data on women from racial or ethnic minority groups. The objective of this study was to examine GWG trends among participants of the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) in Southern California, 84% of whom are Hispanic. We examined WIC administrative data on 27,646 women with full term pregnancies who enrolled in WIC in the first trimester and had their last prenatal WIC visit within one month of their expected delivery date. We examined trends in excessive GWG according to the 2009 IOM guidelines for total weight gain during pregnancy, based on pre‐pregnancy BMI. Overall, 24.6% of women gained above the IOM recommendations, and this percentage varied greatly by race/ethnicity. Among Hispanic English speakers, 30% gained above the IOM recommendations compared to 18.7% of Hispanic Spanish speakers (for all Hispanics, the rate was 23.9%). Among Hispanic mothers less than 20 years of age, 28.9% gained above the IOM guidelines compared to 19.8% of Hispanic mothers aged 35 or older. Rates of excessive GWG were lowest among Asians (16.6%) and highest among, Whites (37.3%), African Americans (37.6%) and Native Americans (38.8%). Among those who started pregnancy overweight or obese, 61.4% gained above the IOM recommendations vs. 13.6% of those who entered pregnancy at a normal BMI. Given the wide reach of the WIC program, WIC administrative data have significant potential to help fill the existing gaps in GWG surveillance. Funding for this research was provided by the USDA FNS through a grant for WIC administered by the CA DPH.
A rapid automated method for detecting likely errors among sequential clinical measures recorded during clinical care
Authors: Schwenke Dawn C.
Published: June 2021

Data recorded during clinical care (CC) are increasingly available for research. However, such data include errors. This study aimed to develop methods to identify errors among sequential measures recorded during CC. Data source were outpatient weights (W, n=1,630,712), heights (H, n=930,282), pulses (P, n=2,124,968), and temperatures (T, n=1,750,158) recorded in electronic medical record from 2000–2010 for 134,948 Veterans receiving care by Phoenix VA Health Care System. Errors were identified by comparing individual values with three within‐person metrics: 1. median (PMed), 2. interquartile range (PIQR), and 3. modified IQR [ModPIQR: PMed + / − smaller of (PMed – 25th percentile) and (75th percentile – PMed)]. Values exceeding cut‐points (>99th or <1st population percentile) for ≥ 2 metric were considered errors. High errors (0.47% W, 0.31% H, 0.52% P, 0.53% T) were median 139%, 109%, 159%, and 103% of PMed; median 4.8, 2.5, 2.8, and 2.2 fold above PIQR; and median 6.9, 30, 3.4, and 2.6 fold above ModPIQR for W, H, P, and T, respectively. Low errors (0.46% W, 0.30% H, 0.45% P, 0.53% T) were 72%, 85%, 62%, and 97% PMed; median 4.2, 7.0, 1.9, and 2.6 fold below PIQR; and median 6.2, 50, 2.4, and 3.0 fold below ModPIQR for W, H, P, and T. This automated method for detecting likely errors in data recorded during CC could be applied to study longitudinal trends in weight/BMI or other clinical measures. Funded by VAHSR&D IIR 02‐286.
A Worksite‐based Weight Loss Intervention for Obesity Prevention
Authors: Salinardi Taylor , Batra Payal , Das Sai Krupa , Robinson Lisa , Lichtenstein Alice H. , Deckersbach Thilo , Roberts Susan
Published: June 2021

Worksites are increasingly being used as locations for implementing healthy diet and weight loss interventions. Hence, there is an urgent need to identify programs that are both successful and sustainable. We conducted a 6‐month pilot randomized controlled trial in overweight and obese employees at 4 worksites (2 intervention; 2 delayed intervention sites) to examine the effects of a worksite‐based intervention on weight loss and changes in cardiovascular risk factors. The intervention combined recommendations to consume a high fiber, low glycemic load diet with education on nutrition and behavior change. Fasting body weight, cholesterol, glucose, and blood pressure were measured at baseline and 6 months in 118 subjects. Results were analyzed using an ANCOVA model with baseline values as covariates. Participants at the intervention sites (n=82) lost significantly more weight (−8.0±6.7 vs. +0.6±2.8 kg, p<0.0001) and had greater decreases in fasting total cholesterol (−13.2±25.0 vs. −2.4±24.2 mg/dl, p=0.0423), fasting glucose (−6.4±13.2 vs. +5.7±18.0 mg/dl, p=0.0006), systolic blood pressure (−8.6±12.6 vs. +5.5±10.8 mmHg, p<0.0001), and diastolic blood pressure (− 8.2±10.9 vs. −0.5±6.7 mmHg, p=0.0007) as compared to participants at control sites (n=33). This worksite intervention resulted in significant weight loss and improvements in cardiovascular risk factors relative to no intervention.

Grant Funding Source: USDA Human Nutrition Research Center
Association between total water intake, micronutrient intakes and serum nutrient profile among U.S. adults
Authors: Yang Meng , Park Sohyun , Chun Ock K.
Published: June 2021

Given the paucity of investigations on nutrient status by water intake, we examined water intake by sociodemographic factors and its association with dietary and serum micronutrient levels among 3,189 US adults (≥20 y). We used two 24‐h dietary recalls and serum nutrient data from NHANES 2005–2006. The daily mean total water intake was 3.1 L, with 68% adults under Adequate Intake (AI) level. Total water intake was higher in adults aged 31–50 y, non‐Hispanic whites, adults with higher BMI, education and physical activity, those taking supplements, alcohol consumers, and current smokers. In multivariate regression analyses, plain water intake was positively associated with food moisture and negatively with beverage moisture (excluding plain water, P<0.001). Beverage moisture was negatively associated with food moisture (P<0.05). Plain water and food moisture intakes were positively associated with Ca, Fe, Mg, vitamin A, C, E, K, B6, niacin and carotenoids (P<0.05), but beverage moisture was unrelated (Ca, Mg, vitamin B6, niacin, α‐carotene) or negatively (Fe, vitamin A, C, E, K, β‐carotene) associated (P<0.05). Concentrations of serum B12, C, E, and carotenoids increased with plain water and food moisture intake (P<0.05) and decreased (P<0.01) or were unrelated with beverage moisture. Various contributors of total water intake differed in their associations with micronutrient intake in adults.

Grant Funding Source : Self‐funded
Quercetin and chlorogenic acid affect butyrate excretion, NF‐ κB activity, and cell proliferation in DSS treated rats
Authors: Piefer Leigh Ann , Weeks B R , Carroll R J , Byrne D H , Ambrus A , Turner N D
Published: June 2021

We previously showed quercetin was protective against colon carcinogenesis via inhibition of pro‐inflammatory molecules. The goal of this study was to explore effects of quercetin and chlorogenic acid (CA), stone fruit bioactives, on short chain fatty acid (SCFA) excretion and cell proliferation regulation in a colitis/injury model. Rats (n=63) received diets (basal, 0.05% CA, or 0.45% quercetin) for 3 wk before dextran sodium sulfate (DSS, 3%, 3x, 2 wk separation, n=11/diet) or control (no DSS, n=10/diet) treatments. SCFA concentration and fecal moisture were measured in feces collected pre‐ and post‐DSS treatments and on day 62. Colons were assessed for injury, inflammation, and proliferative index (PI), and mucosal scrapings for NF‐κB activity. DSS increased fecal moisture by 38.7% and SCFA concentration by 139.6% (p<0.0001). Quercetin, a butyrate uptake inhibitor, tended to increase 24 h butyrate excretion in DSS rats relative to basal (p=0.07) and CA (p=0.09). Quercetin and CA diets increased NF‐κB activity and PI (p<0.05) in control rats. Compared to non‐DSS rats, CA decreased NF‐κB activity and PI in DSS rats (p<0.05). Although quercetin and CA affected butyrate excretion, NF‐κB activity, and proliferation, and had no effect on injury, it may be possible these compounds would mitigate injury if given a longer recovery period. Funded by USDA/NIFA 2008‐34402‐19195 and 2009‐34402‐19195.
Estimated energy intake and energy loss among low‐income formula‐fed infants: Mid‐point analysis of Phase 1 of the “Baby‐Mine” study
Authors: Kavanagh Katherine F , Nicklas Jennifer C , Burney Janie L , Greer Betty P
Published: June 2021

Phase 1 of the Baby‐Mine study focuses on how infant‐feeding practices impact rate of weight gain among 2‐to 4‐month‐old formula‐feeding infants. Low‐income mothers of healthy, term infants < 3 mo of age, who report using reconstituted infant formula, were recruited via fliers distributed to the local health department, pregnancy resource centers, social media websites, and a birth registry. At ~ 2 and ~ 4 months of age, infant intake (and estimated spit‐up) was recorded for 48 hrs, and infant weight and length measured. Mid‐point evaluation was performed using data from the 31 mothers completing both data collection points. Of the 31 infants, 18 were male and 13 female and average birth weight was 3229.3g. At time point 1 (TP 1), infants were, on average, 2.3 months old, weighed 5603g, offered 4.8 oz of formula (consuming 4.3 oz), consumed 624 kcal/d, lost an estimated 8.1 kcal/d via spit‐up, and 29% were offered cereal in the bottle at least once. At time point 2 (TP 2), infants were, on average, 4.1 months old, weighed 7039g, were offered 5.8 oz of formula (consuming 5.1 oz), consumed 700 kcal/d, lost an estimated 8.3 kcal/d via spit‐up, and 54.8% were offered cereal in the bottle at least once. Rate of daily gain, from TP 1 to TP2, was 27.4g, which is higher than the recommended daily gain. Estimated energy loss and inappropriate rate of weight gain are likely to be important targets for nutrition education among new parents. Funds: USDA/NIFA/AFRI Award‐2010‐85215‐20663.
Alpha‐1 antitrypsin reduces ovariectomy‐induced bone loss in mice
Authors: Cao Jay J , Gregoire Brian R , Song Sihong
Published: June 2021

Bone loss occurs in menopause due to the decreased estrogen and increased proinflammatory cytokine production. Alpha‐ 1antitrypsin (AAT) is a multifunctional protein with proteinase inhibitor and anti‐inflammatory activities. To determine whether AAT mitigates bone loss induced by estrogen deficiency, thirty‐eight female C57BL/6J mice (7‐wk‐old), were either ovariectomized or sham‐operated. Ovariectomized animals were randomly assigned to AAT‐injected (n=13; 2 mg/mouse, every 3 days for 30 days) or phosphate buffered saline (PBS)‐injected group (n=12), while sham‐operated mice (Sham; n=13) were injected with PBS and used as controls. Ovariectomy resulted in decreased wet uterus weight (P<0.01), bone loss, increased serum leptin concentrations, and higher body weight (P<0.01) compared to sham. AAT treatment increased tibial trabecular bone volume/total volume and trabecular thickness relative to PBS treatment in ovariectomized mice (P<0.01). Ovariectomized mice with AAT‐injection had higher uterus weight (P<0.01), lower serum osteocalcin levels (P<0.05), fewer bone marrow TRAP‐positive osteoclasts (P<0.05) and less expression of calcitonin receptor (P<0.01) in bone than mice injected PBS. These data demonstrate that AAT reduces ovariectomy‐induced bone loss in mice possibly through inhibiting osteoclast activity and bone resorption.
Racial Differences in Plasma Omega‐3 Long Chain Fatty Acid Levels in a Cohort of African Americans and European Americans with Diabetes and Metabolic Syndrome
Authors: Wilson Bryan Anthony , Sergeant Susan , Ainsworth Hannah , Mathias Rasika , Chilton Floyd H.
Published: June 2021

Background

We have shown that polymorphisms in the fatty acid desaturase 1 gene (FADS1) are associated with racial differences in omega‐6 long‐chain polyunsaturated fatty acid (LC‐PUFA) metabolism. We thus examined whether racial differences also exist in omega‐3 (ω3) LC‐PUFA metabolism.

Methods

We used GLC to measure levels of the LC‐PUFA precursor α‐linolenic acid (18:3, ALA) and the major ω3 LC‐PUFAs eicosapentanoic (22:5, EPA), docosapentaenoic (24:5, DPA) and docosahexanoic (24:6, DHA) acids in fasting plasma from 63 African Americans (AfAm) and 166 European Americans (EAm) with diabetes or metabolic syndrome.

Results

Compared to EAm, AfAm had significantly lower ALA (2.0 ± 1.2 vs 3.1 ± 2.1, p<0.001) and DPA (1.7 ± 0.5 vs 2.0 ± 0.8, p=0.006) levels, whereas DHA levels were significantly higher (6.8 ± 2.6 vs 5.6 ± 2.2, p<0.001). EPA levels were no different. Compared to EAm, fatty acid product:precursor ratios were significantly higher in AfAm for DHA:ALA, 3.8 ± 1.6 vs 2.1 ± 0.9, p<0.001; EPA:ALA, 1.2 ± 0.9 vs 0.8 ± 0.6, p<0.001, and DHA:DPA, 4.1 ± 1.4 vs 3.0 ± 1.0, P<0.001.

Conclusions

As product:precursor ratios of circulating ω3 PUFAs provide a surrogate measure of substrate flux through the LC‐PUFA synthesis pathway, these data suggest that AfAm display enhanced conversion of ω3 precursors to LC‐PUFA, which may be due to genetically‐determined increased activity of the FADS1 desaturase and elongase genes.

Grant Funding Source : NIH Grants: 5P50AT002782‐07, 3P50AT002782‐07S1
Advancing nutrition policy: Challenges and strategies
Authors: Pelletier David , Frongillo Edward A , Gervais Suzanne , Hoey Lesli , Menon Purnima , Stoltzfus Rebecca J , Ahmed Shamshir , Ahmed Tahmeed
Published: June 2021

The Lancet Nutrition Series estimated that global nutritional stunting could reduced by 36% with full implementation of current evidence‐based interventions but little systematic research exists concerning the political and systemic factors that inhibit or enable such implementation. These factors were studied in Bolivia, Guatemala, Peru, Vietnam and Bangladesh through participant‐observation, document review and interviews. Key findings are: a) high‐level political attention to nutrition was generated through varied strategies but political commitment and system commitment remained elusive; b) mid‐level actors from ministries and external partners had difficulty translating political opportunities into concrete implementation plans due to capacity constraints, disagreements over priority interventions, delivery strategies, ownership, roles, and responsibilities; and c) field implementation was severely hampered by capacity constraints from national to front‐line levels. These findings suggest that investments to identify evidence‐based nutrition interventions are unlikely to reduce malnutrition unless there are commensurate investments to understand and address political and systemic capacity constraints that influence implementation. Supported by a grant from The World Bank.
Impacts of RegIIIβ inactivation on murine hepatic protein nitration induced by acetaminophen
Authors: Yun Jun-Won , Lum Krystal , Lei Xin Gen
Published: June 2021

As the mouse homologue of human hepatocarcinoma‐intestine‐pancreas/ pancreatic‐associated protein, RegIIIβ is involved in liver regeneration. Because knockout of RegIIIβ rendered mice susceptible to acetaminophen (APAP) toxicity, we conducted a series of experiments to determine if the protein affected the APAP‐induced hepatic nitrotyrosine formation. At 5 h after mice (8‐wk old, n = 5/group) were injected with APAP (300 mg/kg, ip), the knockout group exhibited stronger hepatic protein nitration than the wild‐type (WT). Meanwhile, pre‐treating the knockout mice with a recombinant RegIIIβ protein (6 mg/kg, ip) at 6 h prior to the APAP treatment greatly attenuated (P < 0.05) the APAP‐induced hepatic protein nitration, hepatic glutathione depletion, and plasma alanine transaminase activity rise. Subsequent characterization of hepatic protein nitration by nitrotyrosine immunoprecipitation followed by mass spectrometry identified 170 unique nitrated protein candidates involved in 48 biological processes in the knockout mice, compared with the WT. In conclusion, RegIIIβ exerted an important role in the APAP‐induced hepatic protein nitration (NIH DK 53018).