bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EVOLUTION OF INSECT BRAINS AND WHY BIG MAY BE BETTER
Authors: Strausfeld Nicholas James
Published: June 2021

Hennigian cladistics, employing neural character sets, corroborating molecular phylogenies, strongly supports the origin of Hexapoda from a marine ancestral stem taxon that is likely to have shared more features with crown Malacostraca than with crown Branchiopoda. Comparative studies of corresponding brain regions show fascinating examples of evolutionary modification and divergence of those centers recognized as supporting multijoint movements, multimodal integration, and allocentric memory. Particularly those brain centers associated with the first true segment of the brain reveal enormous diversity across the Insecta, with some larger species possessing centers comprising hundreds of thousands of neurons and centers that show greatly expanded circuits accommodating novel inputs. The largest and most elaborate brains belong to solitary Hymenoptera, both predatory species and parasitoids. It is these taxa whose survival may be dependent on the ability to counter novel situations with novel behavioral strategies.
Lung developmental biology: an important key to regeneration in apparently adult onset disease
Authors: Warburton David
Published: June 2021

Chronic lung disease is the 4th most common cause of death in adults world wide and the disease burden is increasing, in contrast to cancer and heart disease that are coming under control. Therefore research devoted to finding innovative ways to prevent or treat chronic lung disease should be a major public health priority. The lung develops as an anterior endodermal derivative of the foregut, which undergoes stereotypic rounds of branching morphogenesis in response to complex mesenchymally derived inductive signals. Crosstalk between between the compartments of the lung including mesothelium, mesenchyme, endothelium and nerves need to be correctly coordinated in time and space for morphogenesis to occur in the proper sequence. The same principles apply during alveolarization and postnatal growth of the lung. Severe disruption of this complex program results in absence of the lung, or if somewhat milder, neonatal lethality. Milder yet disruptions interfere with completion of alveolarization, and as a consequence of this confer susceptibility to disease and environmental exposures such as cigarette smoke and particulates. Since lung function falls inexorably past middle age in humans, the original functional endowment determines the starting point for decline. Correct integration of lung progenitor cell function during development is therefore key to prevention of apparently adult onset lung disease, while exogenous stem/progenitor cells, by enhancing regeneration, may be able to stave off the decline or even correct lung function.
USP1 inhibition: a differentiation strategy for Osteogenic Sarcoma
Authors: Dixit Vishva Mitra
Published: June 2021

Inhibitors of DNA binding (IDs) antagonize basic helix‐loop‐helix (bHLH) transcription factors to inhibit differentiation and maintain a stem cell fate. The ID repressor proteins are degraded in differentiated tissues by the ubiquitin‐proteasome system, permitting unimpeded activity of the bHLH family. ID protein expression is elevated in many undifferentiated anaplastic neoplasms, suggesting a mechanism by which ID proteins can escape degradation. Here, we show that the deubiquitinating enzyme ubiquitin‐specific protease 1 (USP1) promotes ID protein stability and stem cell‐like characteristics in osteosarcoma. USP1 knockdown precipitated acute destabilization of ID proteins, cell cycle arrest, and remarkably, induction of an osteogenic differentiation program. Consistent with USP1 functioning in normal mesenchymal stem cells, mice lacking USP1 displayed impaired skeletogenesis, with a pronounced reduction in bone mineralization and total bone volume. In sum, our observations implicate USP1 in preservation of the stem cell state that characterizes osteosarcoma. This malignancy is recalcitrant to traditional chemotherapies so inhibition of USP1 protease activity could represent a novel differentiation therapy.
Changing the Course of America Through Mentoring
Authors: Jones Lovell Allan
Published: June 2021

Over forty years ago, as a new director of the National Institute of General Medical Sciences, Dr. Ruth Kirschstein formed a partnership with Dr. Geraldine Woods and Congressman Louis Stokes to create two ground breaking program, The Minority Biomedical Research Support Program (MBRS), and later, the Minority Access Research Careers (MARC). These stellar programs were the foundation programs to diversify science in America. Yet, forty years later, we are still taking about diversifying science. When I was informed that I was the 2012 Ruth Kirschstein Diversity in Science Honoree, I wonder what she and Dr. Woods would say today about the status of diversity in Science in America. Why has these programs been both successful in raising the numbers, but unsuccessful in changing the landscape of science in our academic institutions. That will be focus of my presentation. The focus will also be on a least one option we should pursue.

In 2002, I realized that I was mining a depleted field. I was taking the survivors of the K – 12 battleground and not enriching the number of underserved students we lose between K ‐ 12. Not changing the fact that we lose between 80 to 85% of our kids interested in science between the 3rd and 4th grade. The object of The Science Centered Inquiry‐Based Educational Activities iN Collaborating Elementary Classrooms (SCIENCE) Project, our early childhood educational component of the PIPELINE Program, is to develop a model to reverse this lost that can be replicated. To link this program with other components of the pipeline that makes science exploration relevant to the underserved. Not that all of these students will become physicians, other health care providers or scientists, but at least they will form the basis for a science education populous.
Hormonal and cellular control of hepatic lipid metabolism
Authors: Rutter Jared
Published: June 2021

We are interested in the mechanisms whereby the body senses its nutrient environment and responds to adapt cellular and organismal metabolism to this changing environment. One maladaptive response to excess feeding is excess fat storage driven by the Sterol Response Element Binding Protein‐1c (SREBP‐1c) transcription factor. SREBP‐1c is activated at multiple levels in response to insulin signaling and stimulates the expression of the entire de novo lipogenesis and triglyceride biosynthesis program. The signaling pathway whereby insulin stimulates SREBP‐1c activity includes the canonical PI3K‐Akt module, but has recently been shown to also depend on the Akt‐dependent activation of the mTOR Complex 1 (mTORC1). We have recently characterized a novel component of this pathway that sheds additional light on how feeding‐induced lipogenesis is controlled.

PAS kinase (PASK) is a highly evolutionarily conserved protein kinase that we have shown to be metabolically regulated and to control glucose‐responsive processes in pancreatic beta‐cells. A mouse lacking PASK, in addition to modest beta‐cell defects, has a profound resistance to the pathological effects of a high‐fat diet. Specifically, PASK−/− mice are protected from the obesity, insulin resistance and dyslipidemia observed in wild‐type mice on a high‐fat diet. The most striking effect that we observed was a loss of the massive hepatic lipid accumulation that occurs on a high‐fat diet. This was accompanied by decreased expression of many of the genes that promote lipid uptake and synthesis in the liver. We demonstrated that PASK strongly regulates SREBP‐1c in cultured cells using a combination of loss‐of‐function and gain‐of‐function approaches and genetics, cell biology and biochemistry. Based on these observations in vitro, we went back to the mouse model and showed that, indeed, the entirety of the SREBP‐1c transcriptional program was decreased in PASK−/− mice. Our preliminary data suggests that PASK regulates SREBP‐1c at the level of proteolytic maturation.

In parallel, we observed that PASK was strongly activated post‐translationally by insulin and that mTORC1 activation was necessary and sufficient for this effect. The current evidence suggests that mTORC1 activates PASK through direct interaction with and phosphorylation. Having found that insulin/mTORC1 activates PASK and PASK activates SREBP‐1c, we then tested whether PASK is a required mediator of the acute insulin/mTORC1 effects on SREBP‐1c and found that it is. My laboratory is now focused on understanding the mTORC1‐PASK‐SREBP‐1c pathway, both the mechanisms of signal transduction and the physiological importance of this pathway.
NAD Metabolism: Mechanisms of lifespan extension in yeast and nicotinamide riboside utilization in a healthy 50 year old man
Authors: Brenner Charles , Trammell Samuel , Mei Szu-Chieh , Migaud Marie
Published: June 2021

More than 100 years after the discovery of the co‐enzyme requirement for glycolysis, more than 70 years after the discovery of niacins, more than 50 years after the discovery of the Preiss‐ Handler pathway of nicotinate utilization, and more than 10 years after the connections between NAD biosynthesis, calorie restriction and aging were discovered in yeast, we continue to find and attempt to fill major gaps in understanding of yeast and human NAD metabolism. In this paper, we will use LC‐MS and genetic analysis to dissect a surprising role for intercellular communication in yeast lifespan extension. We will also present a new chemical synthesis and a first‐in‐man clinical use of nicotinamide riboside, which reveals surprising differences in bioavailability from nicotinamide.
Pilot Study on the Management of Childhood Overweight: A Pound of Cure
Authors: Anzeljc Samantha Ann , Murray Robert
Published: June 2021

Primary care clinicians (PCCs), despite regular access to families with young children, lack a cohesive model for approaching office visits regarding excess weight. Using the 2007 Expert Committee's Recommendations, a set of clinician guidelines on the standard of care for managing childhood obesity, we developed high quality intervention tools for PCC use to direct behavior modification in families with children 2 to 11 years old. We piloted modularized counseling sessions with accompanying educational handouts. To date, we have interviewed 77 families on the counseling sessions and resources. The feedback we obtained guided development of office visit modules and of parental educational materials. On average, motivated families that returned to the clinic needed to complete only 3 to 4 modules, setting 3 goals per visit, to successfully incorporate recommendations into the child's daily life. Of families that returned for follow up visits 41.5%, 37.7%, 13%, and 5.2%, of families completed 2, 3, 4, or 5 office visits respectively. Additionally, of families that attended follow up visits 50%, 37.9%, 60% and 75% of children reduced their BMI percentile as they attended the 2nd, 3rd, 4th, and 5th office visits, respectively. In total, 47% of children attending office visits have either maintained or reduced their BMI.

Grant Funding Source : Medical Mutual of Ohio
ApoER2‐Mediated Endocytosis of Long‐Isoform Selenoprotein P (Sepp1) Supplies Skeletal Muscle Cells with Selenium
Authors: Kurokawa Suguru , McDonald W. Hayes , Hill Kristina E. , Burk Raymond F.
Published: June 2021

Sepp1 transports selenium from the liver to tissues such as testis, brain and kidney. Apolipoprotein E receptor‐2 (apoER2) and megalin, both members of the low‐density lipoprotein receptor (LDLR) family, have been identified as Sepp1 receptors in those tissues. The mechanism of selenium acquisition by skeletal muscle cells is not known. We studied selenium uptake by a rat myoblast cell line. L8 cells took up Sepp1 from the medium and utilized its selenium for the synthesis of glutathione peroxidase (Gpx). However, L8 cells did not take up Gpx3 or the Sepp1 isoform that lacked the selenium‐rich C‐terminal domain. To identify Sepp1 receptors on L8 cells, a solubilized membrane fraction from them was passed over a Sepp1 column. ApoER2 and Lrp1, another LDLR family member, were identified in the column eluate by mass spectrometry. RNAi experiments showed that knockdown of apoER2 inhibited 75Se uptake from 75Se‐labeled Sepp1 while knockdown of Lrp1 had no effect on it. Inhibition of clathrin‐mediated endocytosis suppressed 75Se uptake. Blocking of lysosome acidification did not inhibit uptake of 75Se from 75Selabeled Sepp1 but it suppressed development of Gpx activity by blocking digestion of the endocytosed Sepp1. We conclude that long‐isoform Sepp1 binds apoER2 on L8 cells and is endocytosed and digested in lysosomes to provide selenium to the cells. Supported by NIH grants ES02497 and DK82813.

Grant Funding Source: NIH
Antibiotics induce mistranslation of selenocysteine residue in selenoproteins
Authors: Tobe Ryuta , Naranjo-Suarez Salvador , Turanov Anton A , Carlson Bradley A , Tsuji Petra A , Yoo Min-Hyuk , Everley Robert A , Gladyshev Vadim N
Published: June 2021

Doxycycline (Dox), chloramphenicol (Cp) and Geneticin (G418) are antibiotics which block polypeptide synthesis by inhibiting the elongation step in prokaryotic and/or eukaryotic cells. Tetracyclines, including Dox and Cp have been recently reported to participate in the proliferation of mammalian tumor cells. However, their mechanism in cancer progression remains unclear. The effect of these three antibiotics on cell viability was measured in EMT6 breast cancer cells. After treatment, the expression levels of thioredoxin reductase 1 (TR1), glutathione peroxidase 1 (GPx1) and glutathione peroxidase 4 (GPx4) were analyzed by 75Se and western blot analysis. His‐tagged recombinant TR1, GPx1 and GPx4 were purified from treated cells, specific activity measured, and mass spectrometry analysis used to detect modified sequences. All three antibiotics induced the expression of TR1 by western blot analysis, whereas 75Se‐labeling and enzymatic assays showed a decrease in TR1 expression and activity in treated cells. Mass spec analysis revealed that selenocysteine residues were replaced by other amino acids in an antibiotic dependent manner. These data, along with the results from analysis of GPx1 and GPx4, show that these antibiotics inhibit selenoprotein biosynthesis by replacement of selenocysteine residues. This research was supported by the Intramural Research Program of the NIH, NCI, CCR.
PNPLA3 Gene Expression is Regulated by Carbohydrates and Unsaturated Fatty Acids in vitro and in vivo
Authors: HAO LEI , Ito Kyoko , Wray Amanda E , Mueller Natalie M , Atluri Mokshasree , Ross Catharine A
Published: June 2021

A polymorphism of the patatin‐like phospholipase‐3 (PNPLA3, adiponutrin) gene is strongly associated with non‐alcoholic fatty liver disease. However, the functions of PNPLA3 are not well understood. To examine mechanisms by which nutrients regulate PNPLA3 gene expression, C57BL/6 male mice were fed a normal chow diet (control), a high‐carbohydrate liquid diet, or the same diet with lipid emulsion for 4 weeks. PNPLA3 gene expression was increased ~22‐fold in the high‐carbohydrate diet fed group compared to the control group. However, lipid emulsion completely reversed PNPLA3 induction by the high carbohydrate diet. In HepG2 cells that were cycled between 5.5 and 25mM glucose (starvation and refeeding conditions), PNPLA3 was significantly decreased ~5‐fold by glucose starvation and increased ~2.5‐fold by glucose refeeding, while insulin had no effect. Carbohydrate response element binding protein (ChREBP) expression correlated with PNPLA3 expression. Unsaturated fatty acids, oleic acid and linoleic acid (400 μM, 24 h), each significantly decreased PNPLA3 mRNA by ~50%, but linolenic acid did not, although Oil Red O staining was similar for all fatty acids. We conclude that PNPLA3 is regulated by carbohydrates and certain types of unsaturated fatty acids both in vitro and in vivo, and suggest a role for PNPLA3 in lipogenesis. (NIH CA‐ 90214)

Grant Funding Source : NIH CA‐90214
Female mice lacking active NADPH‐oxidase enzymes are protected against “Western Diet”‐‐induced obesity and metabolic syndrome
Authors: Ronis Martin J , Sharma Neha , Badeuax Jamie , Ferguson Mat , Badger Thomas M
Published: June 2021

NADPH oxidase (Nox) enzymes, have been implicated in regulation of adipocyte differentiation and inflammation in a variety of tissues. We examined the effects of feeding AIN‐93G or a “Western diet” (WD) (45% fat, 0.5% cholesterol) on development of obesity and “metabolic syndrome” in wild type (WT) mice or p47phox −/− mice in which Nox enzymes 1–3 are inactive. Diets were fed between ages 4 and 12 wk. In both male and female WT mice, weight gain, fat pad weight and % adiposity were greater in WD‐fed mice compared to AIN‐93G (P< 0.05). In p47phox −/− mice, while the males behaved similarly to WT, the females were completely protected against the development of obesity and mean adipocyte size was lower than in WT females fed either diet (P<0.05). WD feeding resulted in hyperglycemia and hepatic triglyceride accumulation in WT, but not knockout mice of either sex (P< 0.05). p47phox −/− had reduced hepatic SREBP‐1c and downstream targets: fatty acid synthase and acyl CoA carboxylase mRNAs (P<0.05). These data suggest that signaling through reactive oxygen species derived from Nox enzymes plays an important role in development of obesity and metabolic syndrome particularly in females. USDA, CRIS 6251‐51000‐007‐03S.
Activation of brown adipose tissue by acute and chronic administrations of capsinoids in humans
Authors: Yoneshiro Takeshi , Aita Sayuri , Matsushita Mami , Saito Masayuki
Published: June 2021

Objective

Capsinoids, nonpungent capsaicin‐related substances, are known to increase brown adipose tissue (BAT) thermogenesis and whole‐body energy expenditure (EE), and reduce body fat in small rodents. The objective of this study was to clarify whether BAT is involved in the thermogenic effects of capsinoids in humans.

Results

Eighteen male volunteers underwent fluorodeoxyglucose‐ positron emission tomography after 2‐h cold exposure at 19 °C, and were divided into BAT‐positive and ‐ negative groups. Thermogenic responses to orally ingested capsinoids (9mg) or placebo were examined by indirect calorimetry at 27 °C. Thermogenic responses to cold at 19 °C (CIT) were also examined before and after daily ingestion of capsinoids for 6 weeks.

Results

Oral ingestion of capsinoids increased EE in 1 h by 15.2 ± 2.6 kJ/h in the BAT‐positive group, more than in the BAT‐negative group (1.7 ± 3.8 kJ/h). Placebo ingestion produced no significant change in either group. CIT in the BAT‐negative group was much lower than that in the BAT‐positive group, but it increased after 6‐week capsinoids ingestion.

Conclutions

Oral ingestion of capsinoids increases EE by stimulating and recruiting BAT in humans.
Carbohydrate restriction favorably affects HDL metabolism in men and women with Metabolic Syndrome. Addition of egg yolk further increases large HDL particles
Authors: Andersen Catherine J , Blesso Christopher N , Park Youngki , Barona Jacqueline , Pham Tho , Lee Jiyoung , Fernandez Maria Luz
Published: June 2021

We investigated the effects of carbohydrate restriction (CR) and whole egg consumption on HDL‐cholesterol (HDL‐C), HDL particle size/diameter, and peripheral blood mononuclear cell (PBMC) ATP‐binding cassette transporter A1 (ABCA1) mRNA expression in men and women (n=18) classified with Metabolic Syndrome (MetS). Participants followed a carbohydrate‐restricted diet (25–30% carbohydrate) in addition to daily consumption of either 3 eggs (EGG group) or the equivalent amount of egg substitute (SUB group) for 12 wk. All participants decreased body weight (p < 0.001) and BMI (p < 0.001) over time with no differences between groups. There were also increases in plasma HDL‐C (P < 0.010) over the 12 wk, whereas no changes were observed in either plasma total or LDL‐cholesterol despite greater daily cholesterol intake by the EGG group (p < 0.001). Decreases in body weight and BMI correlated with increases in mRNA expression of ABCA1 (r = −0.587; p< 0.025 and r = −0.579; p< 0.025, respectively). In addition, changes in ABCA1 mRNA expression highly correlated with changes in HDL size (r = 0.763, p= 0.001). There was an increase in both the number of HDL particles and large HDL over time with greater increases in the EGG group (P< 0.05). All participants also had decreases in the atherogenic medium‐sized HDL particle (p< 0.01). These studies support the role of CR and whole egg consumption in improving HDL metabolism in people with MetS.

Grant Funding Source: Egg Nutrition Center
Dietary quercetin supplementation alleviates disease related muscle injury in dystrophic muscle
Authors: Hollinger Katrin , Snella Elizabeth , Shanely R. Andrew , Selsby Joshua T.
Published: June 2021

Duchenne muscular dystrophy is the most common, fatal, X‐linked muscle disease and is modeled by the mdx mouse. Dystrophic muscle shows signs of progressive necrosis and fibrosis leading to a loss of muscle function. Peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) up‐regulation has been shown to alleviate some aspects of dystrophic pathology. Quercetin (QCN), a natural polyphenolic compound derived from foods such as red apples and red onions, is a potent sirtuin 1 (SIRT1) activator capable of entering muscle cells via oral delivery. SIRT1, in turn, activates PGC‐1α by deacetylation. To determine the extent to which a diet containing QCN could alter the progression of disease related muscle injury 3 mo old mdx mice were fed a diet containing 0% or 0.2% QCN for 6 mo, sacrificed, and diaphragms removed. Control and treated mice ate similar amounts of food and grew at a similar rate during the study period. Dietary QCN reduced the number of extracellular nuclei/mm2 by 37% (p<0.05). The number of muscle cells/mm2 was increased by 20% (p<0.05) and muscle cells with centralized nuclei were reduced by 33% (p<0.05) in diaphragms from treated animals compared to control. Fibrosis was similar between groups. These data suggest that dietary QCN is beneficial to dystrophic muscle and warrants greater exploration as a potential therapeutic agent. Partially supported by the Martin Fund.
EGCG protects against 6‐OHDA induced neurotoxicity in a cell culture model
Authors: Chen Dan , Kanthasamy Anumantha G , Reddy Manju B
Published: June 2021

Disruption of iron metabolism may involve in the progression of Parkinson's disease. Our objective was to test whether the protective effect of (−)‐epigallocatechin‐3‐gallate (EGCG) against 6‐hydroxydopamine (6‐OHDA) induced neurotoxicity was by regulating iron homeostasis in N27 cells. EGCG pretreatment significantly protected against 6‐OHDA‐induced neurotoxicity (MTT, SYTOX Green and Caspase‐3 activity assays). EGCG with 6OHDA treatment significantly increased (p<0.0001) TH+ cell count (3.1‐fold) and neurite length (12.5‐fold) compared with 6‐OHDA alone in primary mesencephalic neurons. 6‐OHDA treatment significantly (p<0.05) increased divalent metal transporter‐1 (DMT1), hepcidin, transferrin receptor‐2 (TfR2), H‐ferritin and decreased ferroportin‐1 (Fpn1), TfR1 mRNA expressions. The protein expressions of DMT1, hepcidin and Fpn1 matched with the gene expression data. However, EGCG significantly reversed the effect of 6‐OHDA on above genes and proteins expression. The increased ~2‐fold (p<0.001) 55Fe cell uptake with 6‐OHDA and normalization with EGCG pretreatment confirmed iron burden associated with neurotoxicity and protection by EGCG. In conclusion, EGCG protected against 6‐OHDA induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis. However, further studies are warranted to determine the mechanism of that regulation.

Grant Funding Source : Nutrition Wellness and Research Center
Trends in sources of empty calories for 2–18 year olds in the US: 1977–2008
Authors: Slining Meghan M , Popkin Barry M
Published: June 2021

Much emphasis is placed on reducing consumption of empty calories from added sugars and solid fats. Our objective was to study 30‐year trends in food and beverage sources of empty calories among US 2–18 year olds. One day of nationally representative dietary intake data for each period was examined. We categorized foods with excessive added sugars (≥13% of energy from added sugars), excessive saturated fat (≥9.1% of energy from saturated fat) or both as key sources of empty calories. All analyses use sample weights that reflect the US population aged 2–18 y. The percent of energy consumed by children and adolescents from foods and beverages classified as empty calories remained stable from 1977–2005 (80% of total energy from empty calorie foods), with a slight decrease to 76% by 2008. A concurrent decrease it total calories consumed was observed over the same time period (2003–2008). While per capita consumption decreased, the top sources of empty calories remained consistent across time, namely sugar sweetened beverages, excess fat pizza, excess fat milk beverages, excess fat processed meats, excess fat pasta dishes, excess fat poultry and excess fat cakes, cookies and pies. Substantial increases in intake were observed from 2003‐ 2008 for excess fat tortilla based dishes and cheese. These findings provide important insights on recent improvements in child diet as well as areas that can still be enhanced.

Funding comes from the Robert Wood Johnson Foundation (Grant 67506).
Comparing actual caloric value of food purchases with NHANES: what is missing?
Authors: Piernas Carmen , Ng Shu Wen , Popkin Barry M.
Published: June 2021

Surprisingly little is known about the actual food and beverage choices that US individuals make as reflected in the food and nutrient values of NHANES.

We explored and contrasted total energy intake and energy from beverage groups from two sources of data that monitor food choices in the US: measures of yearly food purchases from 67,570 US households (adults >19 y old) from the Nielsen Homescan Longitudinal dataset from 2005–2008; and intake data from store foods from one 24‐h recall from 10,333 U.S. adults >19 y from NHANES 2005–2008. We developed multiple methodological approaches to derive per‐capita estimates of daily energy intake and kcal from beverages from the Homescan dataset: a per capita, an adult equivalence scale, and a regression‐based marginal consumer approach. Survey commands were implemented in STATA 12 to account for survey design and weighting.

Per‐capita daily energy intake from NHANES surveys is 300 kcal lower than per capita estimates of caloric value of food/beverage purchases from Homescan. We will explore specifics of beverage over/underreporting in depth in the analysis with a focus on rapidly increasing categories such as energy drinks. This study is the first to compare actual purchases of each specific beverage categories with NHANES. Our results add new evidence of the potential effect of recall bias on estimates of caloric intake when using national surveys in nutritional research.

Grant Funding Source : UNC (R01‐CA109831, R01‐CA121152); the Robert Wood Johnson Foundation (Grant 68793) and the National Institutes of Health (R01 HL104580)
Physical activity and protein intake are associated with feelings of energy and fatigue in overweight black and white women
Authors: Ward Christie L , McConnell Whitni J , Larson Rebecca D , O'Connor Patrick J , Evans Ellen M
Published: June 2021

The aim of this study was to examine associations among self‐reported feelings of energy, diet components, physical activity (PA) and adiposity (%Fat) in overweight (BMI: 28.6±2.7 kg/m2) black (B; n=24) and white (W; n=29) women (35.4±5.2 y). Measures included diet via nutritional analysis of 3‐day food records, PA with Godin questionnaire, %Fat via DXA and prior 7‐ day feelings of energy (VIG) and fatigue (FTG) with the Profile of Mood States (Brief) scale. B and W were similar (all p>0.05) in age, PA, %Fat (B=40.0±2.9%, W=41.7±5.0%), energy intake (B=1766±483 kcal, W=1815±450kcal), protein intake (B=71±18 g, W=71±22 g), fat intake (B=63±27 g, W=63±27 g; B=34±5%, W=35±7%) and fruit and vegetable servings per day (B=3.5±1.5, W=3.7±2.9). Fiber intake was lower in B vs. W (14.8±4.2 g vs. 18.9±6.3 g, p=0.01). Though FTG was not different between groups (B=1.7±2.2, W=3.1±3.7, p=0.09), VIG was higher in B vs. W (9.6±5.6 vs. 6.5±5.0, p=0.03). Higher daily protein intake was associated with higher VIG (r=0.3, p=0.04) and lower FTG (r=− 0.3, p=0.02); no other dietary components were related to VIG or FTG (all p>0.05). Higher PA was associated with higher VIG (r=0.3, p=0.04) and lower FTG (r=−0.3, p=0.03). The association of protein and FTG remained after controlling for PA and race (p=0.04) whereas VIG did not (p=0.07). Our data suggest that PA and protein intake may be effective targets to improve feelings of energy and fatigue.
Effects of Ginger (Zingiber officialis L) on Inflammation‐Induced Bone Loss
Authors: Funk Janet L. , Frye Jennifer B. , Wright Laura E. , Timmermann Barbara N.
Published: June 2021

Having previously demonstrated that polyphenolics in turmeric prevent bone resorption in arthritis and osteoporosis, the bone protective effects of structurally‐related polyphenols (gingerols) isolated from the rhizomes of ginger (Zingiber officialis L) were examined using the same experimental rat models. Three extracts were isolated: 1) a crude extract containing gingerols, essential oils and polar compounds, normalized to 26 mg gingerols/kg/d; 2) a gingerol fraction (26 mg/kg/d) and 3) an essential oil fraction (26mg/kg/d). All three extracts were bone protective in streptococcal cell wall (SCW)‐induced arthritis, preventing bone mineral density (BMD) loss as determined by dual energy absorptiometry (PIXIMUS). The crude extract was more effective than the gingerol‐only extract (80% vs. 51% inhibition, p < 0.05). The isolated essential oils were also bone protective (14% inhibition, p < 0.05). Preservation of BMD correlated with antiarthritic efficacy, suggesting that blockade of bone resorption occurred secondary to inhibition of joint inflammation. To test this hypothesis, crude extract was tested in a rat model of ovariectomy‐induced bone loss and found to be without effect. These data suggest that preservation of bone in an experimental model of arthritis occurs secondary to the anti‐inflammatory effects of both the polyphenols and essential oils of ginger. Research funded by NIH (NCCAM/ODS).
The Mother‐Infant Dyad Study: A grounded theory inquiry into the day‐to‐day experiences between first‐time mothers and their infants that influence feeding practices.
Authors: Helvey Jennifer Jean , Bower Katherine M , Kavanagh Katherine F
Published: June 2021

The purpose of this grounded theory study was to explore the experiences that influence infant feeding practices between first‐time mothers and their infants in a low‐income population in the Southeastern United States. Mothers were recruited, via printed flyers and social media websites, and screened for eligibility. Eligibility criteria included first‐time mothers of infants ≤ 12 months of age living in urban areas. In‐depth phone interviews were audio‐recorded, transcribed, and entered into QDA Miner text‐analysis program to facilitate coding. Using grounded theory strategies and emergent coding techniques, transcripts were coded by two independent researchers and coding agreement compared on a predetermined schedule. Interviews were conducted until reaching saturation (n=12). Major, emergent themes include: 1) actions motivated by being perceived as a “good mom” in one's circle, 2) adoption of a feeding schedule until controlled cues are exhibited by the infant (2–4 months of age), and 3) strategies driven by maternal projection that may influence feeding practices. These results will be discussed in detail and offer valuable insight for future programs targeting this population. Funds: University of Tennessee, Knoxville, Professional Development Fund.

Grant Funding Source: University Professional Development Fund
Diet quality of preschoolers and their mothers enrolled in an obesity prevention program
Authors: Laster Leigh Ellen Ruth , Lovelady Cheryl A. , West Deborah G. , Wiltheiss Gina A. , Brouwer Rebecca J.N. , Ostbye Truls
Published: June 2021

Children of obese parents are more likely to become obese than children of normal weight parents. The aims of this study were to determine: 1) diet quality of preschoolers (2–5 y) and their overweight/obese mothers (n=177); 2) if maternal and child diet quality were correlated; and 3) if child's diet quality predicted their BMI. Weights and heights were measured, and two 24‐hr diet recalls were collected. The Healthy Eating Index (HEI)‐2005 was used to measure diet quality. Only 13% of children and 7% of mothers had HEI‐2005 scores ≥ 80, indicating a healthy diet. The majority of children did not meet recommended intake for fruits, vegetables, whole grains, meat and legumes, sodium, saturated fat, and energy from solid fat and added sugars. Child HEI‐2005 scores correlated with maternal HEI‐2005 scores (R2=0.19, p <0.001). However, children and mothers differed in the degree to which they met food group recommendations. Children versus mothers: total vegetables (6% vs. 19%), milk (63% vs. 23%), meat and legumes (33% vs. 61%), and fruits (50% vs. 14%). Child HEI‐2005 scores and energy intake were not correlated with child BMI; only maternal BMI (p=0.02) and education (p=0.03) were significantly related to child BMI. While diet quality was not associated with preschooler BMI, future research is needed to determine if long‐term inadequate diet quality may contribute to excessive weight gain. (NIDDK # R01‐DK075439)
At‐home sugar sweetened beverage consumption in minority, low‐income children and caretakers
Authors: Ferris Ann M , Wei Stephanie , Wakefield Dorothy B
Published: June 2021

Sugar sweetened beverages (SSBs) and over consumption of 100% fruit juice (FJ) add unneeded calories to diets of young children. This study evaluated the amount of SSBs available in the home and the consumption by child and caretaker. Home food inventory and food security assessments of 55 WIC and SNAP eligible caretakers were completed. Caretakers provided food recalls for themselves and their preschool child 3 times at 10‐day intervals at the same time as the home food inventory. The same researcher conducted the food recalls. SSBs recalled were checked against actual home inventory to insure correct identification and analyzed using the Nutrition Data System for Research v. 4.0. Caretakers and children consumed 80% of calories at home. SSBs accounted for 12% (7% from soda) of caretakers and 8% (1% soda) of child's at home intake. Adding FJ increased the daily calories from these beverages to 17% for caretaker and 14% for child. Children's SSB consumption positively correlated with caretaker SSB consumption (r=0.46, p<0.001). Children who consumed SSB with snacks consumed more calories for SSBs and FJ than children who only consumed SSBs at meals, (T (48) =.13, p=.01). The same was not true for caretakers. The significant consumption of SSBs in the home and the parallel between caretaker and child consumption lend credence to targeting the parent as the agent of change for the reduction of SSBs.
Sodium levels in hospital patient menus exceed recommended levels
Authors: Arcand JoAnne , Katherine Steckham , Klin Lori , Nairn Jaclyn , Tzianetas Roula , Newton Gary , L'Abbe Mary R.
Published: June 2021

One strategy to lower population sodium intakes is to develop food procurement policies for publically funded institutions such as hospitals. It is unknown if hospital patient menus contain sodium levels that fall within recommendations. We analyzed hospital patient menus to quantify sodium levels and to determine if these are in agreement with sodium recommendations. We evaluated menus for four diet prescriptions: Regular and Diabetic diets, and 3g‐Sodium and 2g‐Sodium therapeutic sodium diets. We included 84 standard, unselected patient menus and 2234 patient‐selected menus from three acute care hospitals. The sodium content of the Regular, Diabetic, 3g and 2g sodium menus was 2.9±0.6, 3.4 ± 0.5, 2.4±0.4, and 1.5±0.3 g/day for the standard, unselected menus; and 3.0±0.9, 3.6±0.9, 2.5±0.7, and 2.0±0.9 g/day for the patient‐selected menus, respectively. More than 76% of patient‐selected and 86% of standard Regular menus, and 95% of patient‐selected and 100% of standard Diabetic menus exceeded the tolerable upper level (UL) of 2300 mg sodium/day. Most therapeutic sodium menus met prescribed levels; however a higher proportion of menus exceeded the UL when patients self‐selected their menu (p<0.001). In conclusion, the majority of hospital menus contain sodium levels exceeding recommendations, suggesting that hospitals and hospital food manufacturers should participate in sodium‐reduction initiatives.
Extent, intensity and quality of CARE‐India's INHP II/ ICDS program exposure and infant feeding practices in rural Uttar Pradesh, India
Authors: Singh Veena , Ahmed Saifuddin , Dreyfuss Michele , Srivastava Vinod , Chaudhery Deepika , Ahuja Ramesh , Santosham Mathuram , West Keith
Published: June 2021

Evidence of the effectiveness of a scaled‐up nutrition intervention on breastfeeding (BF) and complementary feeding (CF) outcomes is limited. This study provides empirical evidence of the effectiveness of an International non‐government organization (NGO) CAREˈs program in a rural area of India. Utilizing a quasi‐experimental design, a district of CARE program was selected as the intervention and a non‐CARE district with the Government of Indiaˈs Integrated Child Development Services program as the comparison arm. A cohort of 942 mother‐child dyads was followed from birth to 18 months of age. The intervention district showed significant improvement in program coverage of outreach visits by the anganwadi worker (AWW) (40.3 vs. 26.2 at 6 mo), and auxiliary nurse midwife (ANM) (45.4 vs. 30.3 at 6 mo) at all the time periods. Frequency of contacts (¡Ý3) with AWW, and ANM, however, remained low in both arms (<15 vs. <11%). Contact with either of the health care providers showed a positive association with breastfeeding initiation (OR: 2.04–3.08, p=<0.001), adjusted for socio‐demographic and parental education, and caste. An examination of the dose‐response effects suggests that an increase in the number of visits imparts a stronger effect on improving BF initiation. Thus, it is important to improve the operational capacity of nutritional intervention before expecting any improvement in infant feeding practices.
Child food consumption patterns and diet quality in rural Nepal: Effectiveness of a community development intervention
Authors: Fischer Amelia Brennan , Miller Laurie Cass , Rogers Beatrice Lorge , Lohani Mahendra , Singh Padma , Mahato Shubh Narayan , Joshi Neena
Published: June 2021

BACKGROUND

Despite recent improvements in child health, 45% of Nepali children <5 yrs are underweight and 49% are stunted. Community development interventions focusing on household agriculture could improve child diet quality in Nepal, where 82% of the population is rural. This study assesses one such intervention.

AIMS

(1) Examine child diet quality by age, gender, and location in six communities. (2) Assess the early stage impacts of the intervention on child diet quality.

METHODS

Data come from a RCT of a community development intervention in matched rural areas. Serial individual 24‐hr dietary recalls were collected (n=384 households, n=592 children). Analytical methods include multivariate probit and instrumental variables modeling.

RESULTS

Child diet quality varies by agroecological region. Children in agriculturally productive areas increased dietary diversity (DD) from baseline to 12‐months (p<0.001); DD decreased in less productive areas (p<0.001). In less productive regions, children in the intervention areas were more likely to have consumed an animal product in the previous 24‐hours.

CONCLUSION

Benefits in the early stages of community development activities for children may include increased consumption of animal products and increased DD; effects vary by region.

Grant Funding Source: Heifer International
Role of reprogramming factors in transdifferentiation of hepatocytes to biliary epithelial cells
Authors: Bhave Vishakha , Bowen Bill , Michalopoulos George
Published: June 2021

Transdifferentiation of liver epithelial cells (hepatocytes and biliary cells) into each other provides a rescue mechanism in liver disease under situations where either cell compartment fails to regenerate by itself. The mechanisms underlying such transdifferentiation of terminally differentiated epithelial are not known. Recently we reported that adult rat liver expresses reprogramming factors Oct3/4, Nanog, and KLF4, and their expression is important for hepatocyte proliferation and liver regeneration. To test if reprogramming factors play a role in transdifferentiation of hepatocytes to BECs, we used the hepatocyte organoid cultures. In this system, primary hepatocytes when plated on collagen coated roller bottles and cultured in presence of HGF, EGF, and dexamethasone, transdifferentiate to form BECs between 6–8 days in culture. When we looked at the expression of reprogramming factors in this system, we found that Oct3/4, Nanog, and Klf4 are upregulated at day 6 in this system as assessed by mRNA levels suggesting the possible involvement of reprogramming factors in transdifferentiation. Further analysis of protein levels by Western blot, immunohistochemical staining, and intervention studies by blocking reprogramming factors are in progress to elucidate the role of reprogramming factors in transdifferentiation.
Sorting Nexin 27 mediates PDZ‐directed trafficking of Zona‐Occludens (ZO)‐2 to the Tight Junction
Authors: Hueschen Christina Lynn , Zimmerman Seth Paul , Milgram Sharon Lynn , Playford Martin Peter
Published: June 2021

Proteins of the sorting nexin (SNX) superfamily are characterized by the presence of a phox‐homology (PX) domain. SNX27 is unique in being the only sorting nexin to contain a PDZ domain. We used a proteomic approach to identify a novel interaction between SNX27 and Zona Occludens‐2 (ZO‐2, TJP2), a component of the epithelial tight junction. The SNX27‐ZO‐2 interaction requires the PDZ domain of SNX27 and the C‐terminal PDZ‐binding motif of ZO‐2. When tight junctions were perturbed by chelation of intracellular Ca2+, we observed a transient co‐localization of ZO‐1 and ZO‐2 on SNX27‐positive early endosomes. Decreasing SNX27 expression in mpkCCD monolayers caused a decrease in the rate of ZO‐2 mobility, an enhancement of junctional permeability to large solutes, and an increase in the transepithelial resistance of monolayers. In addition to identifying an important new binding partner of SNX27, these findings suggest a role for endocytic pathways in the intracellular trafficking of ZO‐2 and possibly other tight junction proteins. Our results also indicate the involvement of the SNX27‐ZO‐2 interaction in tight junction maintenance and function.
Altered colonic barrier function and paracellular permeability in Muc2−/− mice
Authors: Trusevych Elizabeth Hannah , Hirota Christina , Moreau France , Tran Kim , MacNaughton Wallace , Meddings Jon , Chadee Kris
Published: June 2021

A single layer of epithelial cells connected by tight junctions (TJ) and an overlying layer of Muc2‐containing mucus serve as the intestinal mucosal barrier. In this study, we investigated whether mice lacking Muc2 mucin (Muc2−/−) have a compromised epithelial barrier, increasing their susceptibility to intestinal inflammation. Full thickness colonic tissues from Muc2−/− and Wt mice were mounted in Ussing chambers to access ion transport, transepithelial resistance (TER) and mucosal to serosal flux of FITC‐dextran. TJ proteins were analyzed by Western blot and qPCR. Site‐specific and temporal permeability alterations were measured in vivo using oligosaccharide probes. Ussing chamber studies revealed Muc2−/− mice had increased colonic TER and decreased FITC‐dextran flux when compared to Wt mice, indicating increased barrier function. Of the TJ proteins tested, both barrier‐forming occludin and cation‐selective claudin‐2 protein levels were increased in Muc2−/− colons. However, in vivo oligosaccharide uptake revealed that Muc2−/− mice had increased colonic permeability. Surprisingly, colonic epithelial barrier functions were enhanced in the absence of Muc2 mucin, but in vivo measurements show alterations in colonic permeability that were not identified using ex vivo techniques. These studies suggest that Muc2 mucin confers both luminal and epithelial barrier functions. Support: CIHR, CCFC, AIHS
Attenuation of Intestinal Absorption by Major Efflux Transporters: Quantitative Tools and Strategies Using a Caco‐2 Model
Authors: Lin Xuena , Skolnik Suzanne , Chen Xiaohui , Wang Jianling
Published: June 2021

Efflux transporters expressed in the apical membrane of intestinal enterocytes have been implicated in drug oral absorption. The current study presents a strategy and tools to quantitatively predict the impact of efflux on oral absorption for new chemical entities (NCEs) in early drug discovery. Sixty‐three marketed drugs with human absorption data were evaluated in the Caco‐2 bidirectional permeability assay and subjected to specific transporter inhibition. A four‐zone graphical model was developed from apparent permeability and efflux ratios to quickly identify compounds whose efflux activity may distinctly influence human absorption. NCEs in “zone 4” will probably have efflux as a barrier for oral absorption and further mechanistic studies are required. To interpret mechanistic results, we introduced a new quantitative substrate classification parameter, transporter substrate index (TSI). TSI allowed more flexibility and considered both in vitro and in vivo outcomes. Its application ranged from addressing the challenge of overlapping substrate specificity to projecting the role of transporter( s) on exposure or potential drug‐drug interaction risk. The potential impact of efflux transporters associated with physicochemical properties on drug absorption is discussed in the context of TSI and also the previously reported absorption quotient. In this way, the chemistry strategy may be differentially focused on passive permeability or efflux activity or both.
Provitamin A carotenoid biofortified maize as a source of vitamin A in pregnant and nursing sows (Sus scrofa domesticus)
Authors: Heying Emily , Pixley Kevin , Tanumihardjo Sherry
Published: June 2021

Biofortification is an emerging technique to enhance the nutrient profile of staple crops, while being financially affordable for developing countries. Vitamin A deficiency is a problem of epidemic proportions in many countries and recent studies have emerged to study the efficacy of biofortification of maize to improve vitamin A status. Sows (Sus scrofa domesticus) were given either a biofortified provitamin A maize diet or megadose of retinyl palmitate at the beginning of pregnancy in order to determine the efficacy of maternal‐fetal transfer of vitamin A using these two routes of delivery. Sows were fed the biofortified maize diet throughout pregnancy and lactation, while control sows were fed a vitamin A‐free white maize diet, after receiving the oral vitamin A dose at insemination. Three piglets from each sow were killed at birth and 14 days, and blood was collected at varying time points. Organs collected for vitamin A analysis were liver, lung, spleen, adrenals, and kidneys and analyzed for vitamin A using HPLC methods. Organs and serums are currently being analyzed. Funded by the World Health Organization and HarvestPlus.