bluuebunny/crossref_metadata_2025 huggingface dataset:
Cartilage Imaging and Other Novel Assessments of Bone Repair
Authors: Morgan Elise Feng‐i , Hayward Lauren NM , Hussein Amira I , Gerstenfeld Louis C , Grinstaff Mark W
Published: June 2021

The widespread utility of micro‐computed tomography (μCT) for quantitative, non‐destructive, 3‐D imaging of internal microstructure in highly attenuating materials such as bone, dentin, and coral has inspired new applications of this imaging method. The extension of μCT to study formation of soft tissues during bone healing and bone regeneration will be discussed. In one method, a custom‐designed, cationic, iodinated contrast agent, CA4+, is used to reveal the respective locations and amounts of cartilage, non‐cartilaginous soft tissues, and bone at the site of a bone fracture over the time‐course of healing. This method enables assessment of the early stages of fracture repair, when much of the healing response involves formation of soft tissues, and when formation of bone by endochondral ossification is predominant. In the second method, the intravascular contrast agent Microfil is used for spatial co‐localization of bone and vascular tissues during bone regeneration. Both of these methods require scanning each specimen twice—before and after incubation in CA4+ (first method) or before and after decalcification (second method)—and then subtraction of the two image sets to achieve specific detection of the non‐mineralized tissues of interest. A related method will also be presented that uses sequential μCT scans for quantitative visualization of the fracture process in bone.
Gender and age bias in digital anatomical science education
Authors: Lee Lisa MJ
Published: June 2021

In the current trend of decreasing student‐instructor contact hours in professional science curricula, digital resources are becoming increasingly important. The objective of the study was to investigate professional students’ gender and age bias in the evaluation of instructors based on a digital interaction alone, primarily driven by audio‐delivery of content and without face‐to‐face interaction. Four, twenty‐minute digital learning modules on spinal cord anatomy were created with identical content and script, but each narrated by an individual of different gender and age. After viewing one of the four randomly assigned modules, first year dental students’ quiz performance revealed that the same amount of learning occurred regardless of narrators’ gender and age difference. However, students’ evaluation of instructors based on the audio‐delivery of content in the digital resource revealed a statistically significant negative bias against older female instructor and prejudice in favor of young male instructor. Implications of gender and age bias in digital educational environment should be considered in the design of future clinical and educational workforce model.
The novel zebrafish mutant fantome/wdr43 as a human craniofacial ribosomopathy model
Authors: LaBonty Melissa , Zhao Chengtian , McCann Kathleen , Andreeva Viktoria , Baserga Susan J , Yelick Pamela C
Published: June 2021

Introduction

The zebrafish mutant fantome(fan) exhibits severe pharyngeal arch cartilage defects. Positional cloning was used to map the fan allele to a premature stop codon in wdr43, which encodes a t‐Utp ribosomal protein characterized in yeast to function in rRNA biogenesis. The objective of this study is to use the fantome/wdr43 mutant to define roles for wdr43 in craniofacial development.

Methods

WISH, Alcian blue stain, Y2H, IF histochemistry, shRNA targeted knock‐down, qRT‐PCR, antisense morpholino oligomer (MO), mRNA injections, Western and Northern blot analyses.

Results

The fan/wdr43 mutation was confirmed by rescue with single cell wdr43 mRNA injections, and by anti‐sense wdr43 MO phenocopy. WISH analyses revealed reduced neural crest cell populations, and qRT‐PCR revealed upregulated p53 signaling in fan mutants. In vitro subcellular localization studies showed that full length Wdr43 localized to nucleoli, while truncated fan mutant Wdr43 did not. Stable cell lines expressing shRNAs targeting wdr43 are being used to examine the subcellular localization of other nucleolar phosphoproteins including t‐Utps and Tcof1/Treacle, commonly mutated in Treacher Collins Syndrome.

Conclusions

The fantome/wdr43 mutant exhibits features similar to TCS, and may be an informative model for human neurocristopathies, including TCS.

Support:

NIH/NIDCR R01 DE018043 (PCY).

Grant Funding Source: n/a
ERKonomics: MAPK assets and liabilities
Authors: Cobb Melanie H. , Zaganjor Elma , Dioum Elhadji , Wauson Eric M. , He Min
Published: June 2021

Mitogen‐activated protein kinases (MAPKs) are universal elements of signaling pathways. ERK2 and/or the closely related protein kinase ERK1 are required not only for differentiation, and proliferation, but also for the everyday functions of differentiated cells. ERK1/2 activation kinetics can be manipulated pharmacologically and impact pathway output. Inappropriate activities of ERK1/2 contribute to diseases ranging from cardiofacio‐ cutaneous syndrome to diabetes to cancer. Actions of ERK1/2 in nutrient sensing in pancreatic beta cells contribute both positively and negatively to insulin production by regulating insulin gene transcription and other events at the level of chromatin. ERK1/2 activities are important for proper organization of cytoplasmic organelles and also mediate morphological changes caused by mutant K‐Ras through regulatory events in the cytoplasm.
Structural and functional studies of mRNA processing and quality control
Authors: Tong Liang
Published: June 2021

Eukaryotic mRNA precursors (pre‐mRNAs) must undergo extensive maturational processing, including 5′‐end capping, splicing and 3′‐end cleavage and polyadenylation. Turnover of mature mRNAs is mediated by exoribonucleases that function in the 5′→3′ or 3′→5′ direction (as well as other enzymes), which are important for the degradation of defective mRNAs as well (mRNA quality control). A nuclear 5′→3′ exoribonuclease (XRN2, Rat1 in yeast) also couples pre‐mRNA 3′‐end processing and Pol II transcription termination.

We have been studying the structure and function of various components of the 3′‐end processing machinery as well as the 5′→3′ exoribonucleases. For example, we showed that Ssu72, a Pol II C‐terminal domain (CTD) pSer5 phosphatase, binds a pSer5 peptide with the pSer5‐Pro6 peptide bond in the cis configuration. Moreover, Ssu72 also recognizes the CTD phosphorylated at Ser7, but a pSer7 peptide is bound in the opposite direction as compared to the pSer5 peptide.

Unexpectedly, our studies on a protein factor (Rai1) that stimulates the 5′→3′ exoribonuclease Rat1 led to the discovery of a novel quality control mechanism for mRNA 5′‐end capping. Studies in yeast and mammalian cells confirm that mRNAs with incomplete 5′‐end caps are produced under physiological conditions, and that Rai1 and its mammalian homolog (DXO) have important roles in the detection and degradation of such defective mRNAs.
Control of mRNA metabolism by deadenylation
Authors: Coller Jeff , Al‐Husaini Najwa , Presnyak Vlad , Smith Jenna , Saju Linda , Baker Kristian E.
Published: June 2021

The presence of a polyadenosine tail is an important determinant of mRNA translation and stability. The regulated removal of the tail, i.e. deadenylation, leads to either translational quiescence or mRNA degradation. Deadenylation, therefore, is a critical node in gene expression and is especially important in certain biological contexts such as in the early embryo and in neurons. All mRNAs deadenylate at different rates; some fast, some slow. In addition, deadenylation is enhanced by message‐specific regulatory factors. For instance, many 3’ UTR binding proteins and the miRNA machinery drive post‐transcriptional regulation (in part) by facilitating deadenylation. Despite the importance of deadenylation, little is known about how differential rates of poly(A) tail shortening are achieved. One clue comes from studies that show that mRNA translation rates are intimately connected to deadenylation rate. Our recent work has begun to tease out the complex molecular details that intertwine translation and deadenylation. Moreover, we have concentrated on understanding the function of protein factors that facilitate removal of the poly(A) tail. Deadenylation is catalyzed by the CCR4‐NOT protein complex. The function of distinct members of this complex as well as how these factors influence rates of deadenylation will be discussed.
Probing mechanisms of cell polarity and membrane trafficking using bacterial effector molecules.
Authors: Alto Neal
Published: June 2021

Polarity in mammalian cells emerges from the local assembly of protein interaction networks that control biochemical reactions in space and time. Despite the complexity of these systems however, bacterial pathogens have evolved parsimonious mechanisms to hijack human cell polarity. Here, I will present a tractable model of molecular polarity that is based on the ability of bacterial pathogens to induce localized actin polymerization at the host cell surface. We identify bacterial Type III secreted “effector” molecules that rewire Rho‐family small GTPase signal transduction in space and time. Importantly, molecular polarity is accomplished by assembling proteins onto phospholipid microdomains that function together to generate positive and negative feedback loops. Unexpectedly, our studies indicate that actin polymerization functions as a GTPase signal amplifier involved in generating local membrane protrusive events. By further probing the molecular underpinnings of these biochemical reactions using highly evolved bacterial molecules, we have uncovered principles in cell biology that may be extended to natural cell polarity and membrane trafficking systems.
Metabolic Pathway Analysis in Cancer
Authors: DeBerardinis Ralph J
Published: June 2021

Reprogramming of cellular metabolism is a hallmark of malignancy. Understanding the metabolic transitions that accompany cellular transformation will lead to new insights into the biological basis of transformation, and may generate new targets for therapy and diagnostic imaging in cancer. We use a combination of NMR spectroscopy and mass spectrometry to analyze tumor cell metabolism in culture, in mouse models of cancer, and in human patients. Analysis of nearly 100 individual cell culture models uncovered a surprising amount of cell‐autonomous metabolic heterogeneity, but also demonstrated that most cancer cells can be stratified into a finite subset of metabolic platforms according to how they metabolize glucose and glutamine, two abundant extracellular nutrients that account for the bulk of carbon and nitrogen metabolism in cancer cells. We have now developed isotope tracing methods to probe intermediary metabolism in live tumors, both in mice and in humans. This work revealed the appearance of many of the same metabolic activities in vivo as those observed in cultured cells, including glucose oxidation, anaplerosis, and amino acid synthesis. Our ongoing work seeks to develop methods to translate these findings into novel imaging approaches to diagnose cancer and monitor the response to therapy.
Molecular classification of triple negative breast cancer
Authors: Lehmann Brian D , Bauer Josh A , Chen Steven , Shyr Yu , Sanders Melinda , Pietenpol Jennifer A
Published: June 2021

Triple negative breast cancer (TNBC) represents 10–20% of all breast cancers that lack estrogen receptor (ER) and progesterone receptor expression as well as amplification of the human epidermal growth factor receptor 2 (HER2). TNBCs more frequently affect younger and African‐American women and are more aggressive. Targeted therapies exist for ER‐positive and HER2‐amplified breast cancers, however treatment options for TNBC are limited by a lack of molecular understanding of this disease. To gain insight into the biology of TNBC, we compiled transcriptional profiles of 587 TNBCs and classified this disease into six molecular subtypes. We identified representative cell lines for each TNBC subgroup and targeted prominent signaling pathways. We identified two basal‐like subgroups characterized by cell cycle and DNA damage response genes and cell lines preferentially responded to cisplatin. Two mesenchymal‐like subgroups were enriched in differentiation, epithelial‐mesenchymal transition and growth factor pathways. We described an immunomodulatory subgroup, defined by immune cell markers and signaling genes. We identified a subgroup driven by androgen receptor (AR) signaling and PIK3CA mutations, rendering cell lines sensitive to AR antagonists and PI3K inhibitors. These data will aid in clinical trial design and biomarker selection for alignment of TNBC patients to appropriate targeted therapies.
Biochemistry students’ misconceptions regarding enzyme‐substrate interactions
Authors: Linenberger Kimberly J. , Bretz Stacey Lowery
Published: June 2021

Enzyme‐substrate interactions are fundamental concepts that span various topics in biochemistry and molecular biology (e.g., kinetics, metabolism, and translation). Deficiencies in understanding of enzyme‐substrate interactions could hinder students’ understandings of later concepts in biochemistry. Misconceptions detected during interviews with biochemistry students were used to create the Enzyme‐Substrate Interactions Concept Inventory (ESICI) in order to be able to efficiently measure a large number of students’ understandings. The ESICI was administered to N=707 biochemistry students at 16 institutions across the United States. Twenty specific misconceptions measured by the ESICI fall within five categories: enzyme and substrate characteristics, types of complementarities, enzyme conformational change, where and to what an inhibitor binds, and how the enzyme interacts with the substrate. Four specific misconceptions were selected by more than 37% of students, and 85% of students held misconceptions in three or more categories. This presentation will focus on findings from both student interviews and the ESICI of one of the most prevalent misconceptions, the role of shape and charge in enzyme‐substrate interactions.
Tuning tRNA Sequences for Optimal Translation
Authors: Uhlenbeck Olke
Published: June 2021

The approximately 50 different bacterial tRNAs are structurally quite diverse despite acting as fairly equivalent substrates of the ribosome. We hypothesize that much of this structural diversity has evolved to compensate for the differing physical properties of the esterified amino acid and the codon‐anticodon interaction such that each tRNA can function with similar rate and accuracy. Interestingly, the sequences of tRNAs possessing the same anticodon are also highly diverse among different bacteria suggesting that multiple evolutionary “solutions” are available to optimize tRNA function. Our progress in understanding how the sequences of tRNAs are “tuned” in translation will focus on their interaction with EF‐Tu on and off the ribosome and their ability to efficiently decode the correct codon while avoiding incorporation at incorrect codons.
The role of Lipid transfer proteins in membrane trafficking and signal transduction
Authors: Lev Sima , Kim SoHui , Kedan Amir , Selitrennik Michael , Keinan Omer
Published: June 2021

Lipid transfer proteins (LTPs) were initially discovered as soluble factors that accelerate the transfer of different lipid species between membranes in vitro. Since then, many LTPs have been isolated, cloned, crystallized and extensively studied for over 30 years. The mechanisms by which LTPs transfer lipids between bilayers in vitro have been established by numerous studies. Yet, their actual functions in intact cells remain largely controversial. Extensive studies on LTPs from plants, yeast and mammals suggest that LTPs regulate multiple cellular processes including vesicular trafficking, signal transduction and lipid metabolism. Our studies on certain LTPs with different lipid‐transfer specificity demonstrated their influence on intracellular lipid distribution; shed light on their mechanisms of action in intact cells, and their coordinated lipid transfer activity. Furthermore, our studies on the Nir2 protein, a large protein consisting of an N‐terminal phsphatidylinositol (PI)‐transfer domain, demonstrate its regulatory role in membrane trafficking events and signal transduction cascades. We will discuss our recent findings and describe our general view on LTPs and their mode of action in intact cells.
RhoA and Rap1 mediate GPCR crosstalk to integrins and cell growth
Authors: Brown Joan Heller , Yu Olivia , Stupack Dwayne , Sayyah Jacqueline
Published: June 2021

Agonists for a subset of G‐protein coupled receptors (GPCRs), including thrombin, S1P and LPA, elicit receptor coupling to G12/13 family proteins which stimulate exchange factors to activate RhoA. We have explored novel downstream signals by which RhoA links GPCRs to cell growth. One pathway involves RhoA mediated transactivation of the matricellular protein Cyr61/CCN1. CCN1 is secreted from the cell and signals through integrins. We have shown that CCN1 signaling through α5β1 integrins is required for thrombin induced proliferation of 1321N1 glioblastoma cells. Integrin signaling is also regulated from inside‐out through activation of another small G‐protein, Rap1. Thrombin signaling to RhoA leads to sustained activation of Rap1 and increases cell adhesion and integrin signaling through Rap1, suggesting that GPCRs also engage integrin mediated pathways from within the cell. Rap1 also plays a central role in GPCR mediated glioblastoma proliferation both in vitro and in vivo. Rap1a siRNA treatment significantly attenuates thrombin stimulated DNA synthesis in two glioblastoma cell lines. Furthermore lentiviral shRNA to Rap1a markedly inhibits growth of both cell lines in a mouse xenograft model. We are currently exploring the role of GPCR signaling through RhoA, Rap1 and integrins in glioblastoma tumor cell growth in vivo.
Protein turnover in pregnant pigs at amino acid intake in excess of requirements
Authors: Moehn Soenke , Rafii Mahroukh , Pencharz Paul B , Ball Ronald O
Published: June 2021

Ten experiments to determine amino acid (AA) requirements of pigs in early and late pregnancy were evaluated to determine which factors affected protein turnover when the test AA intake was above requirements. In all experiments, each of 6 to 7 sows were fed 6 diets with graded levels of test AA in both early and late gestation. Protein turnover was determined based on 13C enrichment after oral L[1–13C]phenylalanine (Phe) dosing using a stochastic model. The observations (max n=200) were evaluated using mixed models (SAS). The final models fit the data with r2 = 0.79 (protein synthesis, S) to r2 = 0.87 (Phe oxidation, Ox, g/d). Greater AA and Phe intake increased (P < 0.05) S, breakdown (B) and Phe flux. Ox and B decreased as pregnancy progressed (P < 0.02), while S, flux and Phe retention (RPhe) increased (P<0.08). Interactions (P<0.02) between AA intake, Phe intake and gestational age increased S, flux and RPhe, indicating a need for more AA towards term. Greater metabolizable energy (ME) intake increased flux (P = 0.003) but decreased B (P = 0.001) in interaction with AA intake (P < 0.02). Thus, pregnant sows can use more AA at higher ME intake. Ox was greatest (P = 0.001) in the 3rd parity but was reduced (P < 0.03) by interactions with increasing BW, ME intake and gestational age. Thus, Phe kinetics may change from adolescent to adult sows. More AA and ME than stated in requirements may be needed close to term when sows carry large litters.
Omega 3 Fatty Acids and White Matter Mediated Cognitive Decline in Older Adults
Authors: Bowman Gene , Dodge HIroko , Kaye Jeffrey , Quinn Joseph
Published: June 2021

Objective

Omega 3 PUFAs may work on vascular pathology mediated cognitive decline, including brain white matter lesions and executive skills. We examined whether PUFAs are associated with cognitive domains (executive function and processing speeds) historically sensitive to the accumulation of white matter hyperintensities (WMH).

Methods

This cohort study of 86 non‐demented subjects used the Trail Making Test Part B to represent executive function and the Digit Symbol test for processing speed. Plasma eicosapentaenoic acid (EPA, 20:5n‐3) and docosahexaenoic acid (DHA, 22:6n‐3) were analyzed using GC and combined to form a PUFA index. WMH burden was measured as the total volume of WMH on MRI. Cognitive change was examined using mixed effects models.

Results

At baseline, the mean age and MMSE were 86 and 28, respectively. Sixty‐two percent were female, 11% had at least one APOE4 risk allele and mean follow up was 4 years. The PUFA index was associated with a 1‐year delay in executive decline attributable to age after multivariate adjustment (p = 0.01). The significance of this index to executive decline was lost after adding WMH volume to the model (p = 0.89), while WMH remained a strong predictor of executive decline (p = 0.02).

Interpretation

Higher intake of PUFA may slow the decline in executive function by reducing WMH lesions in people at risk for dementia.
Mediterranean diet adherence and cognitive functioning in an Australian sample
Authors: Murphy Karen Joy , Crichton Georgina E , Bryan Janet , Hodgson Jonathan M
Published: June 2021

A Mediterranean diet is reported to promote longevity, reduce mortality, and may improve cognition. In a retrospective cross sectional study with 1183 Australians, aged 40–65 years, we examined relationships with Mediterranean diet (MedDiet) adherence and self‐reported cognitive function and psychological well‐being. Dietary data were collected from a validated food frequency questionnaire and used to calculate mean intakes of foods included in a MedDiet and foods typically consumed in an Australian diet. Adherence to a MedDiet was determined based on an 11‐point scale. Measures of cognitive function and psychological well‐being included self‐esteem, anxiety, stress, memory functioning, cognitive failures, general health and physical function. 72% of the Australian sample had a medium (4–11 points) adherence to a MedDiet. Overall MedDiet adherence was not related to cognitive function. However intakes of plant foods, a major component of a MedDiet, was positively associated with measures of physical function (P=0.021) and general health (P<0.001), and negatively associated with trait anxiety (P=0.015), depression (P=0.012) and perceived stress (P=0.016). A substantial proportion of the diet in this Australian sample came from foods not typically consumed in a MedDiet. This is a major limitation when attempting to compare MedDiet adherence across populations.
Low plasma vitamin B6 predicts cognitive decline and depression in at‐risk individuals
Authors: Scott Tammy Maria , Tucker Katherine L
Published: June 2021

Vitamin B6 (PLP) is essential in many aspects of brain function such as neurotransmitter synthesis, receptor binding, macronutrient metabolism, and gene expression, and deficiencies have been associated with higher levels of inflammation and risk of atherosclerosis. The objective of this study was to assess whether low plasma PLP concentration (< 30 nm/L) was a risk factor for cognitive decline in the Boston Puerto Rican Health Study cohort (n=1148; 28% male; mean age = 57.1y (SD ± 7.6). 30% (n=347) of participants had low PLP status. Low PLP was associated with smoking, diabetes, and higher BMI (p≤ 0.001 for all), as well as higher plasma homocysteine (Hcy) (p≤0.05), C‐reactive protein (CRP) (p≤0.001) and white blood‐cell (WBC) count (p≤0.05). Low PLP status was predictive of 2 year decline in executive cognitive function (≥ 1 SD decrease in cognitive testing composite score) [OR = 1.73 (95% CI 1.04 – 2.87), p=0.033] and with a similar trend for memory [OR = 1.62 (95% CI 0.97 – 2.80), p=0.086], adjusting for baseline cognitive score, demographics, vitamins B9, B12, C, and D, and diabetes, hypertension, depression, Hcy, CRP, WBC and lifestyle variables. PLP quintile was inversely related to depressive symptoms severity (β=‐0.673, se±0.31; p=0.029) and perceived stress (β=−0.552, se±0.22; p=0.010) in similar full models. Low PLP status remains a risk factor for cognitive decline and depression in at‐risk populations.
Chicken ovalbumin upstream promoter transcription factor II regulates the expression of retinoic acid receptors and retinoid X receptors in hepatocytes
Authors: Li Rui , Chen Guoxun
Published: June 2021

Chicken ovalbumin upstream promoter transcription factor II (COUP‐TFII, nuclear receptor 2F2), a member of the nuclear receptor superfamily, has been shown to affect glucose homeostasis in genetic knockout studies. It has been suggested that COUP‐TFII may modulate the retinoid signaling pathway, which is primarily mediated by retinoic acid receptors (RARα, β, and γ) and retinoid X receptors (RXRα, β, and γ). We hypothesize that COUP‐TFII interacts with retinoid signaling system. To test it, primary rat hepatocytes were infected with recombinant β‐galactosidase or COUP‐TFII adenovirus for 18 h, and treated without or with 5 μM all‐trans retinoic acid (RA) for 6 h. The mRNA levels of RARs, RXRs and their target genes, Srebp‐1c and Pck1 were determined using real‐time PCR. COUP‐TFII over‐expression reduced the basal mRNA levels of Rara, Rxra, and Rxrb by 88%, 58%, and 88%, respectively, without affecting those of Rarb and Rxrg. RA induced the mRNA levels of Rarb and Rxrg by 10.3‐ and 6.4‐fold, respectively, with no effects on those of Rara, Rxra, and Rxrb. Interestingly, over‐expression of COUP‐TFII abolished the RA‐induced mRNA expression of Rarb, Rxrg, Srebp‐1c and Pck1. These data indicate that COUP‐TFII can negatively regulate RA signaling at least in part by inhibiting the expression of RARs and RXRs. The interaction between COUP‐TFII and retinoid signaling may play a role in controlling fuel homeostasis.

Grant Funding Source: American Heart Association
Alternate day fasting with a high fat diet: Impact on body weight, body composition, and coronary heart disease risk profile in obese adults
Authors: Klempel Monica C , Kroeger Cynthia M , Varady Krista A
Published: June 2021

Background

Alternate day fasting (ADF) with a low‐fat (LF) diet is effective for weight loss and cardio‐protection. However, the applicability of these findings is questionable as most Americans consume a high‐fat (HF) diet. This study examined if these beneficial changes in weight and coronary heart disease (CHD) risk can be reproduced if a HF diet is used in place of a LF diet during ADF.

Methods

Thirty‐two obese subjects were randomized to an ADF‐HF (45% fat) or ADF‐LF diet (25% fat), which consisted of two phases: 1) a 2‐week baseline weight maintenance period, and 2) an 8‐week ADF weight loss period. All food was provided to subjects.

Results

Body weight was reduced (P < 0.0001) by ADF‐HF (5 ± 1%) and by ADF‐LF (4 ± 1%). Fat mass decreased (P < 0.0001) by ADF‐HF (5 ± 1 kg) and ADF‐LF (4 ± 1 kg). Fat free mass remained unchanged. Waist circumference decreased (P < 0.001) by ADF‐HF (7 ( 1 cm) and ADF‐LF (7 ( 1 cm). LDL cholesterol and triacylglycerol concentrations were reduced (P < 0.01) by both interventions (ADF‐HF: 18 ( 5%, 14 ( 5%; ADF‐LF: 24 ( 3%, 14 ( 4%). The proportion of small LDL particles decreased (P < 0.05) in the ADF‐HF and ADF‐LF groups by 8 ( 3% and 10 ( 4%.

Conclusion

Thus, an ADF‐HF diet produces similar reductions in weight and CHD risk as an ADF‐LF diet. These findings are important in terms of diet tolerability and long‐term adherence to ADF diets.
Effect of META060, a substituted 1,3‐cyclopentadione compound derived from hops, in the management of obesity
Authors: Tripp Matthew L , Lerman Robert H , Darland Gary , Konda Veera R , Desai Anuradha , Chang Jyh‐Lurn , Lamb Joseph J
Published: June 2021

In search of phytochemicals with anti‐inflammatory properties – which may also be useful in obesity management – we discovered candidate META060, a family of substituted‐1,3‐cyclopentadiones derived from hops. In vitro, META060 inhibited kinases (e.g. PI3Kβ/δ/γ, GSK3α/β, BTK and SYK) involved in NF‐κB pathway and reduced NF‐κB nuclear abundance. It reduced inducible COX‐2 and iNOS abundance and PGE2 and nitric oxide production in LPS‐stimulated macrophages. In vivo, META060 reduced acute and chronic inflammation in arthritic mice, and lowered fasting glucose and insulin in db/db mice at parity to Metformin. In mice fed a high‐fat diet, META060 prevented weight gain (including liver weight gain and subcutaneous/epididymal fat accumulation), reduced metabolic endotoxemia, and up‐regulated tight junction proteins zonula occludens‐1 and occludin. We designed a randomized controlled trial to test META060 (400 mg/day t.i.d. versus placebo) on short‐term weight loss (Phase 1) and long‐term weight maintenance (Phase 2) in obese individuals. Phase 1 was a 12‐week ketogenic style (high‐protein, low‐carbohydrate) weight loss program (1000–1100 calories/day); Phase 2 a 52‐week lifestyle program without caloric restriction. Preliminary data showed that at the end of Phase 2, participants receiving META060 retained 107% of the mean 26.5 lb (11.5% body weight loss) lost during Phase 1. Supported by Metagenics Inc.
The System L1 amino acid transporter (SLC7A5) facilitates nutrient signalling in mouse skeletal muscle in vivo
Authors: Poncet Nadege , Taylor Peter Maving
Published: June 2021

The System L1‐type amino acid transporter (LAT1; catalytic subunit SLC7A5) mediates transport of large neutral amino acids (LNAA) in many mammalian cell‐types. LNAA such as leucine are required for full activation of the mTOR‐S6K signalling pathway promoting protein synthesis and cell growth.

We investigated the role of intracellular LNAA delivery by the LAT1 transporter for mTOR‐S6K pathway activation in skeletal muscle using muscle‐specific (MCK Cre‐mediated) SLC7A5 knockout (KO) mice and wild‐type littermates fed for 10 weeks (to age 105 days) with diets of 10, 20 or 30% protein. Food intake and growth rate were similar for all groups. In muscle‐specific SLC7A5‐KO mice, Leu and Ile concentrations in gastrocnemius muscle were reduced by 35% and Gln increased by 27% (relative to wild‐type) as dietary protein content was reduced from 30 to 10%. These changes were associated with >;50% decrease in S6K Thr389 phosphorylation in SLC7A5‐KO muscle, indicating reduced mTOR‐S6K pathway activation, despite no difference in lean tissue mass between genotypes on the same diet.

SLC7A5 modulates LNAA‐dependent muscle mTOR‐S6K signalling in mice, although it appears non‐essential for maintenance of normal muscle mass.
ADOLESCENTS PURCHASING FOOD AWAY FROM HOME
Authors: Racine Elizabeth F , Mueffelmann Rebecca
Published: June 2021

Background

Adolescents often have their own money. Spending on food away from home may influence their health status.

Objective

To examine factors associated with purchasing food away from home among adolescents

Design

Cross‐sectional analyses using 2007 Panel Survey of Income Dynamics, Child Development Study data (n=1,181). Adjusted logistic regression was used.

Results

In general older age, higher levels of parental education, and drinking more juice and less milk were associated with purchasing food away from home. Among younger adolescents (12–16 yrs) being Black and having a history of food insecurity were associated with purchasing food away from home; while living in the inner city, being lower income, participating in the Food Stamp Program, being overweight/obese, and eating more fruit were associated with not purchasing food away from home. Among older adolescents (16–19 yrs) being middle income (vs. high income), being overweight/obese, and having better health status were associated with purchasing food away from home; while being Hispanic, having a history of food insecurity, drinking more milk, and usually eating a hot lunch at school were associated with not purchasing food away from home.

Conclusions

Targeting nutrition education to adolescents with greater likelihood to purchase food away from home may be useful.

This analysis was not funded.
Higher cognitive and gross motor scores in Chinese toddlers randomized to meat compared to either micro‐nutrient fortified or unfortified infant cereal as first complementary food
Authors: Krebs Nancy F , Sheng Xiaoyang , Westcott Jamie E , Hu Yan‐Qi , Liu Shan‐Shan , Hambidge K Michael
Published: June 2021

Objective

To compare developmental outcomes in rural poor Chinese infants randomized to 3 different complementary feeding (CF) regimens from 6–18 mo of age.

Methods

Subjects were from a cluster randomized CF trial conducted in Xichou, Yunnan. 6 mo old infants were assigned to meat (50g/d pork, (M)), equi‐caloric micronutrient fortified cereal (FC), or local non‐fortified rice cereal (UC). Bayley Scales of Infant Development (BSID), 3rd edition, were performed at 12 and 18 mo of age. BSID testing was conducted by a core team of research workers trained and supervised by a pediatric psychologist experienced with BSID testing in this setting.

Results

A subset of subjects was tested at 12 mo of age; no differences by group were identified in any of the 3 BSID scales. At 18 mo, 85–91% of participating subjects underwent testing. Analysis by Kruskal‐Wallis; results by group in table, mean (SD).

Conclusion

Results support a potential developmental benefit of meat over cereal including a micronutrient fortified product.

Support: Thrasher Research Foundation; Shanghai Key Lab of Ped GI & Nutr; Nat'l Natural Sci Foundation of China
Retinoid derivatives offer anti‐inflammatory benefits by promoting neutrophil apoptosis and inhibiting proinflammatory mediator production in a model of bovine respiratory disease
Authors: Duquette Stephanie , Fischer Carrie D , Feener Troy D , Barreda Daniel R , Morck Douglas W , Nickerson James , Buret Andre G
Published: June 2021

Clearance of apoptotic neutrophils (PMN) following infection is critical for the resolution of inflammation. Despite demonstrating immunomodulatory properties, the effects of retinoids in PMN in the context of an inflammatory response remain unknown.

Objective

to evaluate the immunomodulatory properties of two retinoids, oxidatively‐transformed carotene‐β (OxC‐β) and retinoic acid (RA) in a model of Mannheimia haemolytica‐induced bovine respiratory disease, which is characterized by severe inflammation.

Results

in vitro, RA and OxC‐β induced caspase‐and time‐dependent apoptosis, but not necrosis, in bovine PMN, but not epithelial cells or fibroblasts. Neither RA nor OxC‐β affected PMN function. In M. haemolytica‐infected calves (2×107 CFU), animals that received a 28‐day dietary OxC‐β treatment (10 mg/kg) had elevated apoptotic leukocytes and reduced LTB4 levels in their lower airways 3h post‐infection vs infected‐untreated calves.

Conclusion

RA and OxC‐β promote cell‐specific apoptosis and inhibit the production of pro‐inflammatory LTB4, both mechanisms that promote the resolution of inflammation, thereby suggesting an anti‐inflammatory role for retinoid derivatives. Supported by NSERC and AIHS.
Old‐onset Energy Restriction is Detrimental to NK Cell Maturation
Authors: Roman Brooke Elizabeth , Clinthorne Jon , Duriancik David , Gardner Elizabeth M
Published: June 2021

Even though young adult‐onset energy restriction (ER) has been shown to increase lifespan, we have previously reported increased susceptibility to influenza infection due to impaired NK cells in young mice. Other research suggests that there may be a benefit to young adult‐onset vs. old‐onset ER in preventing T cell senescence in rhesus monkeys. The aims of this research were to determine if aging exacerbates the impaired NK cell phenotype observed in ER mice, as well as determine if there is an optimal age of ER onset to prevent NK cell defects associated with aging. Male C57Bl/6 mice were analyzed at 22 mo, 40% ER began at either 4 mo (young adult‐onset, standard NIA protocol) or 20 mo (old‐onset). Aged ER mice had significantly increased immature (CD127+/CD27+CD11b−) NK cells in the lung and spleen, and significantly decreased mature (CD27‐CD11b+) NK cells in the lung, spleen, liver, and bone marrow compared to aged AL mice. Additionally, old‐onset ER is more detrimental to NK cells than young‐onset ER, as evidenced by increased immature (TRAIL‐DX5+) and decreased mature (TRAIL+DX5‐) NK cells in the bone marrow, lung, and spleen. Here we show that in aging, ER results in less mature NK cells, especially with old‐onset. Because NK cells are crucial to innate protection against viruses such as influenza, ER may lead to decreased protection from these immune challenges.

Grant Funding Source: R01AG034949 (E.G.)
Calcium retention in Mexican American adolescents on a range of controlled calcium intakes
Authors: Palacios Cristina , Martin Berdine R , McCabe George P , McCabe Linda , Peacock Munro , Weaver Connie M
Published: June 2021

Objective

There are gender and racial differences in bone calcium accretion in response to calcium intake in adolescents. Mexican American adolescents are an unstudied group and are important because of the high risk of osteoporosis in this growing sector. We determined calcium retention in Mexican American adolescents in response to a range in calcium intakes.

Methods

21 boys and 20 girls 12–15 y participated in a 3‐wk balance study testing a range of calcium intakes (600–2300 mg/d) in a crossover study design with a 2‐wk washout period. Calcium retention was calculated as dietary calcium intake minus the calcium excreted in feces and urine over the last 2 wks.

Results

Boys were taller and had higher lean mass, usual calcium intake and bone mineral content compared to girls, while girls had higher tanner score and fat mass compared to boys (p<0.05). Urinary calcium excretion increased with calcium intake at a greater rate for girls than for boys (p=0.0231). Fecal calcium excretion increased with calcium intake at the same rate for boys and girls (p<0.0001). Calcium retention increased with calcium intake at the same rate for boys and girls (p<0.0001). At the current RDA (1300 mg calcium/d), the predicted calcium retention would be 377 mg/d. In conclusion, calcium retention increased with calcium intake with no gender differences in the slopes in MA adolescents.
Estimating Iron Bioavailability from the US Diet
Authors: Armah Seth M , Carriquiry Alicia , Reddy Manju B
Published: June 2021

Iron bioavailability from the US diet has been estimated to be 18%, which is based on one human absorption study. However, there is a need to reevaluate that value based on the recent data. In this study we estimated iron bioavailability from the US diet using a complete diet‐based algorithm. We used dietary intake and biomarker data from the National Health and Nutrition Examination Survey, MyPyramid Equivalents database, and the Food and Nutrient Database for Dietary Studies to estimate nonheme iron absorption for individuals. Means were estimated using appropriate weights and Taylor Series Linearization was used to estimate variances. We used two different approaches to estimate total absorption. In one approach, nonheme iron absorption was adjusted to 15 μg/L serum ferritin; in the second approach, estimates were made separately for iron deficient and iron sufficient subjects. Geometric mean of nonheme iron absorption was 3.7%. When adjusted to ferritin level of 15μg/L, total absorption (assuming 25% heme absorption) was 15.8%. Based on the second approach, total iron absorption was highest (18%) for iron deficient women 19–49 years, and lowest (4%) among iron sufficient men (ferritin >; 15 μg/L) 19 years or older. This study provides useful data for evaluating the current value of iron bioavailability from the US diet, and is relevant in setting iron intake recommendations.

Grant Funding Source: None
African American community members sustain favorable blood pressure outcomes through 12‐month telephone motivational interviewing (MI) maintenance
Authors: Landry Alicia S , Thomson Jessica , Zoellner Jamie , Connell Carol L , Madson Michael B , Yadrick Kathy
Published: June 2021

Community approaches offer promise for addressing disparities experienced by African Americans in hypertension prevalence, treatment, and control. HUB City Steps, a community‐based participatory research lifestyle intervention, tracked participants through a 12‐month MI maintenance phase following a 6‐month intervention targeting physical activity and adoption of a healthier, culturally congruent diet, in which all participants received MI, social support, pedometer diary self‐monitoring, and five education sessions. This analysis explored whether 18‐month health outcome changes differed between those randomized to a maintenance group with a low (i.e., quarterly; n=134) vs. high (i.e., monthly; n=135) dose of MI telephone calls. Because there were no significant differences between groups, outcome changes were assessed with all participants combined. Significant improvements were apparent for blood pressure, body composition, and fitness measures. Results suggest a low dose of MI is as effective as a high dose of MI to sustain health improvements resulting from a lifestyle intervention. Funding source: National Institute for Minority Health and Health Disparities, R24MD002787.
Dietary Quality and Obesity: Is there a Socioeconomic Gradient in U.S. Adults?
Authors: Zhang Libin , Camhi Sarah M. , Shi Ling , Hayman Laura L
Published: June 2021

Background

Higher social class and better dietary quality (DQ) are linked to lower risks of obesity in the U.S., yet whether effects of DQ on obesity vary by socioeconomic gradients is unknown.

Purpose/Methods

To investigate socioeconomic gradients in how DQ affects obesity, we analyzed data from 2003–2010 National Health and Nutrition Examination Survey (N=13,924) of adults (20–85 years). DQ was assessed with the Healthy Eating Index (HEI) score based on 12 dietary criteria calculated from one‐day dietary recall, and then recoded into three categories: good (>;80 percentile), needs improvement (51–80 percentile) and poor (0–50 percentile). We first studied the association between DQ and sociodemographic profiles, then compared the risk and trend of obesity by HEI categories in the total sample, and stratified by income and education, adjusting for sociodemographic factors and accounting for NHANES sample weights and complex survey design.

Results

38.13% of survey participants were obese. Most participants had poor DQ (weighted mean HEI=50.35, SE=0.22) suggested poor DQ of most participants. Higher DQ was observed among older adults, women, whites, nonsmokers, higher income (≥$45,000) and education (≥high school) groups. Compared to good DQ, poorer DQ was associated with a graded increase in risk of obesity (OR=1.19; 95% CI, 1.04–1.37 for DQ that needs improvement and OR=1.44; 95% CI, 1.23–1.68 for poor DQ) after adjusting for sociodemographic factors. The association between DQ and obesity were the strongest for low income and low educated groups (OR=1.75; 95% CI, 1.33–2.30; all p‐trends and p‐interactions <0.001).

Conclusion

The association between DQ and obesity varies by socioeconomic gradients. Dietary interventions to reduce obesity risk should be more focused on lower socioeconomic groups.
Effects of exercise on fasting triglyceride‐rich lipoproteins from hepatic and intestinal origin
Authors: Egli Léonie , Lecoultre Virgile , Theytaz Fanny , Schneiter Philippe , Tappy Luc
Published: June 2021

A high fructose intake increases fasting triglyceride‐rich lipoproteins (TRL). This is due, at least in part, to a stimulation of hepatic de novo lipogenesis and TRL secretion. Unlike in rodents, the role of the enterocytes in fructose‐induced de novo lipogenesis and TRL secretion remains not established in humans. We therefore assessed the effects of a high fructose diet on fasting blood triglyceride (TG) and apob48 concentrations as well as TRL (sf 20–400) TG content. Since exercise may prevent carbohydrate‐induced dyslipidemia, we measured the effects of an isocaloric, high fructose diet both with and without daily exercise in 8 healthy male subjects.

A fasting blood sample was obtained after 4 days on a low‐fructose diet without exercise (control, C), a 30% fructose diet and no exercise (HFr), and a 30% fructose diet with aerobic exercise (HFrEx).

HFr increased apoB48 from 4.55 ± 0.73 to 8.13 ± 0.94 μg/mL, total TG from 0.65 ± 0.07 to 0.94 ± 0.14 and TRL‐TG from 0.43 ± 0.07 to 0.69 ± 0.13 mmol/L (all p<0.05 vs C). HFrEx completely prevented the effects of HFr and restored fasting apoB48 concentrations (5.29 ± 0.85), TG (0.63 ± 0.06), TRL‐TG (0.37 ± 0.06), to values comparable to those observed after C (all p=NS vs C).

Our data suggest that the gut contributes to fructose‐induced de novo lipogenesis, and can adapt to short‐term changes in the diet and to exercise.

Swiss National Science Foundation supported this work.
Composition of Dietary Fat Source Shapes Gut Microbiota Architecture and Alters Host Inflammatory Mediators in Mouse Adipose Tissue
Authors: Huang Edmond , Leone Vanessa , Devkota Suzanne , Wang Yunwei , Brady Matthew , Donovan Sharon , Chang Eugene
Published: June 2021

High‐fat diet consumption has a significant impact on the development of obesity and inflammation. Studies have shown that dietary factors alter gut microbiota resulting in metabolic and immunologic effects within the host through adipose tissue. The objective of this study is to address how consumption of specific high saturated (SFA) and polyunsaturated (PUFA) fat shapes the intestinal microbiota and how these changes affect adipose tissue‐mediated inflammation.

Adult male C57Bl/6 mice were fed SFA and PUFA diets for four weeks. Body mass and food consumption data were collected weekly. Bacterial DNA from stool samples was extracted and analyzed by T‐RFLP and HiSeq methods. Adipose depots were excised and analyzed for lipogenic and inflammatory gene expression via qRT‐PCR.

Mice fed high‐fat diets showed increased caloric consumption and weight gain compared to low‐fat fed mice. High‐fat diets also resulted in a dramatic shift in gut microbiota, stratifying based on the specific source of dietary fat. These changes led to significantly altered expression of inflammatory markers (MCP‐1, CD192, resistin, APN) in adipose depots.

Collectively, our findings show that gut microbiota resulting from dietary modulation of fat source can influence inflammatory outcome and should be considered a potential therapeutic target to alleviate obesity‐induced inflammation.

Grant Funding Source: T32 DK07074
Moderate alcohol consumption alters hepatic AdipoR1/SREBP‐1c and SIRT1 activity in rats with pre‐existing NASH
Authors: Nascimento Andre Ferreira , Blanche IP , Luvizotto Renata AM , Wang Xiang‐Dong
Published: June 2021

This study investigated whether the detrimental effect of moderate alcohol intake is due to alterations of adiponectin/Adiponectin receptor (AdipoR)/Sirtuin 1 (SIRT1)‐related signaling and lipid metabolism in the livers. Rats were fed with a high‐fat diet (HFD, 71% total energy (TE) from fat) for 6 weeks to induce NASH, and then divided into two sub‐groups: fed either a modified high‐fat diet (HFD, 55% TE from fat and 16% TE from dextrin) or a modified high‐fat alcoholic diet (HFA, 55% TE from fat and 16% TE from ethanol), for additional 4 weeks. We found that, in comparison to HFD group: 1) plasma adiponectin was lower in the HFA group although this change reached a statistical tendency (p=0.06); 2) HFA significantly decreased hepatic AdipoR1 but not AdipoR2; and 3) hepatic FAS mRNA and SREBP‐1c protein levels were significantly up‐regulated, while both DGAT1/2 and CPT‐I mRNA expressions were down‐regulated in HFA. Interestingly, HFA increased hepatic SIRT1 protein levels but significantly decreased SIRT1 activity. In conclusion, the data suggest that the down‐regulation of Adiponectin/AdipoR‐related signaling and SIRT1 activity contribute to the alcohol intake‐exacerbated liver injuries in rats with pre‐existing NASH. (Supported by USDS/ARS:1950–51000‐064S; FAPESP:2011/21664–9)