bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbe‐Host Crosstalk between Short‐Chain Fatty Acids and Intestinal Epithelial HIF Provides a New Mechanism to Augment Tissue Barrier Function
Authors: Zheng Leon , Kelly Caleb , Campbell Eric , Saeedi Bejan , Scholz Carsten , Bayless Amanda , Wilson Kelly , Glover Louise , Kominsky Douglas , Magnuson Aaron , Weir Tiffany , Ehrentraut Stefan , Nguyen Vu , Taylor Cormac , Colgan Sean
Published: June 2021

The interactions between the enteric microbiota and distal gut play important roles in regulating human health. Short chain fatty acids (i.e. butyrate) are produced by anaerobic microbes and are a major energy source for the colonic epithelium. Decreased concentrations of butyrate is strongly associated with colonic disease. Interestingly, the low oxygen conditions that enable butyrate production also place unusual metabolic demands on the colonic mucosa. However, the colonic epithelium is uniquely adapted to this austere oxygen environment through the stabilization of hypoxia‐inducible factor (HIF) and expression of HIF target genes. Because anaerobes are the major producers of butyrate, we hypothesized that microbe‐derived butyrate regulates host HIF. Studies with human intestinal epithelial cells (IECs) revealed that butyrate promotes mitochondrial‐dependent oxygen consumption and stabilizes HIF1α. Furthermore, butyrate activated HIF target genes in IECs and antibiotics decreased butyrate and HIF expression in the mouse colon. Germ free mice also showed decreased HIF1α expression in the colonic epithelium. Finally, we found that butyrate rescues physiologic hypoxia and protects the intestinal barrier via HIF. This indicates that butyrate participates in a diverse set of functions in the gut, including regulation of barrier function, and could be a potential therapeutic for mucosal protection.
Plg‐RKT Deficient Mice Exhibit Defective Macrophage Migration and Plasminogen Binding
Authors: Miles Lindsey , Baik Nagyung , Khaldoyanidi Sophia , Bai Hongdong , Parmer Robert
Published: June 2021

Plg‐RKT is a novel transmembrane plasminogen receptor that binds plasminogen via a carboxy‐terminal lysine residue. In order to evaluate the role of Plg‐RKT in vivo we generated Plg‐RKT‐/‐ mice using homologous recombination and backcrossed the mice ten generations into the C57BL/6J background. The mice were viable and fertile. Among 2,340 littermates from heterozygous matings 611 were Plg‐RKT+/+ (26%), 1,136 were Plg‐RKT +/‐ (49%) and 593 were Plg‐RKT ‐/‐ (25%). This distribution was not significantly different (P>0.05, Chi‐square test) from the expected Mendelian 1:2:1 ratios and indicate equal viability at 3 weeks of age of Plg‐RKT +/+, Plg‐RKT +/‐, and Plg‐RKT ‐/‐ mice. Hematological parameters were determined. There was no effect of genotype on activated partial thromboplastin time, prothrombin time, plasma plasminogen and fibrinogen levels or hematocrit. Plasminogen binding to mouse macrophages was evaluated using quantitative fluorescence activated cell sorting. Plasminogen binding to Plg‐RKT ‐/‐ macrophages was only 20% of that of Plg‐RKT +/+ macrophages (Bmax = 16,386 ± 1,315 molecules/cell and 81,399 ±9,585 molecules/cell, respectively). Furthermore, macrophage migration to the peritoneum 72 hr following thioglycollate injection was 60% less in Plg‐RKT ‐/‐ mice compared to Plg‐RKT +/+ littermates. In conclusion, Plg‐RKTis required for plasminogen binding and macrophage migration in vivo, key features of the inflammatory response.
BALB/c and C57BL/6 Mice Develop Distinct Levels of Tissue Retinol Depending on Growth Stage and Dietary Vitamin A Exposure
Authors: Wei Cheng‐Hsin , Li Yaqi , Ross A Catharine
Published: June 2021

BALB/c and C57BL/6 mice are two of the most commonly used inbred strains for immunology and cancer research; however, there is no comprehensive study on their tissue response to dietary vitamin A (VA) from birth to adult age. The objective of this study was to investigate two factors, age and dietary VA exposure over a range from VA‐deficient (VAD), marginal (VAM), adequate (VAA), to supplemented (VAS) diet, on tissue retinol levels. AIN‐93 VAM diet was fed to BALB/c and C57BL/6 dams from pregnancy until their pups were weaned on postnatal day (P) 21. After weaning pups were randomly assigned to one of the 4 diet groups above. Plasma and tissues were collected at P0, P14, 4 wk, and 8 wk of age and total retinoid concentrations were determined by Ultra Performance Liquid Chromatography (UPLC). For liver and lung, neonates accumulated retinol in tissues from birth to P14, even though all were fed by VAM dams. After weaning, plasma retinol was elevated only in the VAS groups of both strains. Liver and lung total retinol was significantly higher at 4 wk and higher still at 8 wk in both BALB/c and C57BL/6 mice fed VAA or VAS diet. Other tissues including spleen, brown adipose tissue (BAT), and small intestine were capable of storing high levels of total retinol under VAS condition. Overall, liver and lung accumulated VA dose‐dependently: VAD < VAM < VAA < VAS. Interestingly, both strains of mice accumulated VA even when fed a VAM diet. These result help to explain the observations that mice are difficult to deplete of retinol even when fed a VAD diet, and show that several organs accumulate high levels of VA in an age‐ and dose‐dependent manner.
Mechanisms of Mammalian Middle Ear Ossicle Transition from the Reptilian Jaw Joint
Authors: Urban Daniel , Sears Karen
Published: June 2021

During synapsid evolution, postdentary elements in the reptilian jaw transitioned into the middle ear of early mammals. Separation from the dentary allowed unconstrained evolution of the middle ear ossicles, resulting in increased hearing sensitivity and amplified frequency range. Given the importance of such an innovation, it is essential to understand the evolutionary pathway that led to the current phenotype, as this has implications for understanding the development of all mammals. Using an extant model system, Monodelphis domestica, we investigate the developmental basis of the definitive mammalian middle ear. We utilize micro‐CT imaging to characterize the morphological events underpinning the transition, cryosectioning and immunohistochemistry to identify cellular processes behind the morphological events, and laser capture microscopy followed by RNA Sequencing to identify changes in gene expression driving the cellular processes. Among our findings are: decreasing size and rearward movement of the middle ear ossicles appear to be false illusions created by the continued growth and expansion of the surrounding skull elements; separation of Meckel's cartilage from the malleus, occurring at postnatal day 20, is facilitated by apoptosis and is a prerequisite for the onset of hearing; separation and functional changes are due to alterations in timing and expression levels of key genes.

Supported by NSF Graduate Research Fellowship and Doctoral Dissertation Improvement Grant.
The Evolution and Development of The Mandibular Coronoid Process in Mammals
Authors: Anthwal Neal , Tucker Abigail
Published: June 2021

The coronoid process of the mammalian dentary bone is an evolutionary novel structure reflecting the new role of the dentary in mammals as an attachment site for the muscles of mastication. Previous studies have shown that the size and shape of the coronoid is correlated to the bite force required by the adult animal, and is dependent upon the mechanical force acting upon it during development. However little is known about the developmental programme leading to the specification of the process

We demonstrate that the paired homeobox transcription factor Pax9 is expressed in the ossifying front of the future coronoid process, and that Pax9 expressing cells contribute to the coronoid process, but not the other mandibular processes. In Pax9 mutants the coronoid is absent, however the temporalis muscle, which attaches to it, develops normally. Histological and gene expression studies indicated that the muscle attachment site remains. Loss of the coronoid is therefore driven by changes in the intrinsic patterning of the bone. In contrast other mouse mutants lacking the coronoid, such as the Tbx1 null, loss of the coronoid is a consequence of the loss of the muscle acting on the developing bone. Changes to this structure can therefore be influenced by intrinsic and extrinsic factors. The relative size of the coronoid process varies considerably across mammals, with herbivores, such as the guinea pig having a reduced or absent coronoid, while carnivores can have extremely large coronoid processes. The contribution of genes such as Pax9 and Tbx1 to changes in size of this processes on other mammals have therefore also been investigated. Our data implicates cooption of Pax9 in to the osteogenic program of the dentary enabled the development of the coronoid process, a key component in the emergence of the novel jaw.
Fibrinogen Regulates MMP‐9 Processing of VEGF‐induced Angiogenesis and Tumor Growth in Osteosarcoma
Authors: Moore Stephanie , Ohba Tetsuro , Cates Justin , Cole Heather , Mignemi Nicholas , ichikawa Jiro , Hirotaka Haro , Schwartz Herbert , Schoenecker Jonathan
Published: June 2021

Purpose

Osteosarcoma (OGS) is the most common primary malignant bone tumor in children and adolescents. Traditionally, fibrin, the essential structural matrix protein of a blood clot, is thought to enhance tumor adhesion and provide a matrix to support tumor growth. Evidence strongly supports that major angiogenic factors, such as vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP‐9), can bind fibrin in a concentration‐dependent manner. Therefore, we designed experiments to determine the effects of fibrin on OGS tumor angiogenesis by interacting with VEGF and MMP‐9.

Methods

Aggressive murine OGS cells are intratibially injected into Balb/C mice. OGS establishment is determined by radiographic analysis, micro‐CT, histology, and angiography.

Results

Opposed to traditional beliefs surrounding fibrin's role in tumor establishment, this work has shown that the loss of fibrin promotes the proliferation and vascularity of OGS, therefore promoting tumor establishment and disease progression.

image

Therefore, we have confirmed that fibrin does play a role in tumor angiogenesis through its interaction with VEGF, however we have also shown for the first time that MMP‐9 is a novel intermediary factor for this interaction.

Conclusions

In this study, we have demonstrated that fibrin can inhibit tumor angiogenesis by inhibiting MMP‐9 activity and by sequestering VEGF that is cleaved by MMP‐9. This finding demonstrates a novel synergistic relationship between fibrin and MMP‐9 in the progression of OGS, while also identifying new therapeutic targets.
Sensorimotor Integration in Anatomy and Function during Feeding
Authors: German Rebecca
Published: June 2021

The entire feeding sequence, from ingestion through the swallow, is integrated at many levels, including anatomical, functional and neural control. In particular, the transition from oral transport to pharyngeal swallow involves a coordination of multiple musculoskeletal elements, sensory input to and motor signal from several cranial nerves and brainstem nuclei. While excellent work exists on various isolated portions of feeding, such as ingestion, mastication or the pharyngeal swallow, it is not clear what is missed when we fail to consider the entire sequence across different levels of organization. Infant suckling is a simplified model with two distinct behaviors: sucking and swallowing. Analysis of normal performance, as well as the impact of interruption of oral sensation and interruption of pharyngeal sensation on performance provides insights into integration. These results suggest complex sensorimotor integration in the brainstem and that performance of one function is highly dependent on performance of the others.
Mass Spectrometry in Structural Biology: Surface‐induced Dissociation/Ion Mobility of Protein Complexes
Authors: Wysocki Vicki , Quintyn Royston , Harvey Sophie , Song Yang , Yan Jing , Ju Yue , Tanimoto Akiko , Sahasrabuddhe Aniruddha
Published: June 2021

Characterization of the overall topology and inter‐subunit contacts of protein complexes, and their assembly/disassembly and unfolding pathways, is critical because protein complexes regulate key biological processes, including processes important in understanding and controlling disease. Conventional structural biology methods such as X‐ray crystallography and nuclear magnetic resonance provide high‐resolution information on the structures of protein complexes and are the gold standards in the field. However, other emerging biophysical methods that only provide lower resolution data (e.g. stoichiometry and subunit connectivity) on the structures of the protein complexes are also important. Native mass spectrometry is one of these approaches that provide lower resolution, but critical, structural information with high throughput. The power of native MS increases when coupled to ion mobility (IM‐MS), a technique that measures rotationally averaged collisional cross sections and thus direct information on conformational changes. This presentation illustrates a new approach, surface‐induced dissociation/ion mobility (SID/IM) MS, for characterization of topology, intersubunit connectivity, and other structural features (degree of unfolding) of multimeric protein complexes.
ATRX Promotes Binding of PRC2 to Xist RNA and Polycomb Targets
Authors: Lee Jeannie , Sarma Kavitha , Cifuentes‐Rojas Catherine , Ergun Ayla , del Rosario Amanda , Jeon Yesu , White Forest , Sadreyev Ruslan
Published: June 2021

X‐chromosome inactivation (XCI) depends on the long noncoding RNA Xist and its recruitment of Polycomb Repressive Complex 2 (PRC2). How PRC2 specifically interacts with Xist and other Polycomb targets remains elusive. Using XCI as a model, we take an unbiased proteomics approach to search for new Xist and PRC2 regulators. We identify ATRX and show that ATRX is a high‐affinity RNA‐binding protein that directly interacts with RepA/Xist RNA to promote loading of PRC2 in vivo. The Xist gene is a hotspot of ATRX occupancy. Without ATRX, PRC2 cannot load onto Xist RNA nor spread in cis along the X‐chromosome. Epigenomic profiling reveals a dependency of PRC2 on ATRX that extends beyond XCI. Depleting ATRX results in genome‐wide disruptions to PRC2 localization. PRC2 is displaced from genes and redistributed to intergenic space, causing derepression of Polycomb responsive genes. Thus, ATRX is a required specificity determinant for PRC2 targeting and function.
Structural Basis of Bile Acid Transport
Authors: Zhou Ming
Published: June 2021

Bile acids are synthesized from cholesterol in hepatocytes and secreted through the biliary tract into the small intestine, where they aid in absorption of lipids and fat‐soluble vitamins. Through a process known as enterohepatic recirculation, more than 90% of secreted bile acids are then retrieved from the intestine and returned to the liver for resecretion. In humans, there are two Na+‐dependent bile acid transporters involved in the enterohepatic recirculation, the Na+‐ taurocholate co‐transporting polypeptide (NTCP; also known as SLC10A1) expressed in hepatocytes, and the apical sodium‐dependent bile acid transporter (ASBT; also known as SLC10A2) expressed on enterocytes in the terminal ileum. Both NTCP and ASBT utilize the Na+ gradient to drive concentrative transport of bile acids. In recent years, ASBT has attracted much interest as a potential drug target for treatment of hypercholesterolemia, because inhibition of ASBT reduces reabsorption of bile acids, thus increasing bile acid synthesis and consequently cholesterol consumption. To understand the structural changes associated with the coupled transport of Na+ and bile acids, we solved two structures of an ASBT homologue from Yersinia frederiksenii (ASBTYf) in a lipid environment, which reveal that a large rigid‐body rotation of a substrate‐binding domain gives the conserved ‘crossover’ region, where two discontinuous transmembrane helices cross each other, alternating accessibility from either side of the cell membrane. This result has implications for the location and orientation of the bile acid during transport, as well as for the translocation pathway for Na+.
Lipid Transport Involving Chloroplast Envelope Membranes in Plants and Algae
Authors: Benning Christoph , Hurlock Anna , Warakanont Jaruswan
Published: June 2021

Lipid trafficking between the endoplasmic reticulum (ER) and chloroplasts is essential in plant cells and involves two transport complexes in the inner and outer envelope membrane, respectively. The TGD1,2,3 ABC transporter complex so named after the accumulation of trigalactosyldiacylglycerol in the Arabidopsis mutants, consists of a permease (TGD1), an ATPase (TGD3), and substrate binding protein (TGD2). It is located in the inner envelope membrane, but TGD2 is proposed to reach out to the outer envelope membrane to facilitate lipid transfer. TGD4 forms a complex in the outer envelope membrane. TGD2 as well as TGD4 bind phosphatidic acid. However, the actual transported substrates remain to be defined. Novel in vivo and in vitro approaches are applied to address this issue.

Until recently, the green alga Chlamydomonas was not thought to utilize lipid precursors from the ER for the assembly of chloroplast lipids. However, the isolation and analysis of a TGD2 loss‐of‐function mutant of Chlamydomonas suggest that ER to chloroplast lipid transfer takes place in this alga. However, phenotypes of the respective mutants in Arabidopsis and Chlamydomonas differ in specific aspects that may shed new light onto the function of these complexes in Chlamydomonas and Arabidopsis.
Microbiome in Inner‐City Asthma
Authors: Lynch Susan
Published: June 2021

Prevalence of childhood asthma has increased dramatically over the past several decades in Western nations, and particularly in inner city populations. Evidence has emerged for both local environmental exposure in infancy and early life gut microbiome disturbances as associated with childhood allergic asthma development. This has led to the hypothesis that the house dust microbial environment of infants may influence their developing gut microbiome in a manner that alters the risk for childhood allergic disease and asthma development. We have recently demonstrated that house dust microbiome composition varies across inner‐city homes and that this variability is significantly related to allergic disease development in children raised in these environments. Children who develop atopy and recurrent wheezing at age three lack environmental microbial exposures in their house dust that are encountered by children who do not develop these disease phenotypes. The majority of these organisms enriched in allergy‐protective households have been previously described in the human gut microbiome. Moreover, murine studies have demonstrated that exposure of mice to dust from allergy protective households, alters the composition of the gut microbiome in a manner that protects against airway allergen challenge. A specific species, Lactobacillus sakei, found to be significantly enriched in the gut microbiome of these protected animals, was capable of conferring airway protection against both allergen and respiratory viral infection in animals supplemented orally with this species. Hence the growing evidence supports a strong role for household microbial exposures as playing a role in shaping gut microbiome composition in early infancy, in a manner that influences mucosal adaptive responses to a variety of airway insults.
A Systems Approach to Dissecting Immunity
Authors: Aderem Alan
Published: June 2021

The innate immune system is critical for host defense but, when dysregulated, can cause severe inflammatory disease. Inflammatory sequelae are mitigated at a number of levels. Principal among these are the precise identification of the threat and the appropriate tailoring of the response. Infectious agents are identified by a variety of pattern recognition receptors that recognize conserved molecular patterns characteristic of the microbe which are not found in the host. Modulation of the response requires multiple levels of regulation that include crosstalk and feedback among various signaling pathways and gene regulatory networks that operate at distinct temporal scales. Systems biology provides a framework in which this complexity can be addressed. By applying unbiased analytical techniques to global datasets generated from a variety of innate immune cell types under a wide range of conditions, we have identified many genes that are likely to be central regulators of the immune response. In the first part of my presentation I will illustrate the use of systems biology to identify and explore novel anti‐viral and anti‐bacterial immune networks. In the second part of my talk I will demonstrate the application of systems biology to rational vaccine design. Current approaches to making vaccines are similar to those used by Jenner more than 200 years ago in which a related, weakened or dead form of the infectious agent or a component of the pathogen is used to elicit immune memory. Some vaccines have been very successful and have resulted in the virtual eradication of scourges such as smallpox, diptheria, polio, and measles. Other vaccines have failed, most notably those against HIV, tuberculosis, and malaria. The current approach is essentially trial and error and has not been accompanied by a fundamental understanding of precisely how protection arises. This lack of understanding has hampered progress in the redesign of unsuccessful vaccines. Data will be presented that support the argument that systems biology offers a new approach to address the complexity of the immune system and will provide the tools for rational vaccine design. Systems approaches will also speed up vaccine trials, streamline and improve the manufacture of vaccines, and aid in field‐testing.
Mechanism and Function of DHHC Palmitoyltransferases
Authors: Linder Maurine , Gottlieb Colin , Malgapo Martin , Greentree Wendy
Published: June 2021

Members of a family of integral membrane proteins characterized by a DHHC (Asp‐His‐His‐Cys) motif catalyze the addition of palmitate or other long chain fatty acids onto cysteine residues in intracellular substrate proteins. DHHC proteins are a highly diverse family with 23 members in humans. Conserved features include at least 4 transmembrane spans and a cysteine‐rich domain (CRD) that is exposed on the cytoplasmic face of membranes. The biomedical importance of members of this family is underscored by their association with intellectual disability, Huntington's Disease, and cancer in humans and raises the possibility of the enzymes as targets for therapeutic intervention. Our prior work showed that DHHC proteins form an acyl‐enzyme intermediate prior to transferring the acyl group onto substrate proteins. The DHHC cysteine is necessary for both autoacylation and transfer. In cells, we showed that both wild type DHHC3 and the catalytically inactive DHHS3 (C157S) mutant enzyme are palmitoylated, suggesting that cysteine residues other than C157 are palmitoylated. DHHC proteins oligomerize, suggesting a mechanism for intermolecular palmitoylation, and potentially accounting for palmitoylation of the DHHS3(C157S) mutant in cells. Using mass spectrometry, we directly identified palmitate modification of C146 in DHHC3, a conserved residue in the CRD. Mutation of C146 or other conserved cysteines in the CRD compromised autoacylation and transfer of palmitate. These mutations resulted in structural perturbation, as identified by limited proteolysis experiments. These findings suggest that palmitoylation of residues other than the catalytic cysteine may play an important role in structuring the CRD to enable enzyme activity.
Effect of Fermentable Carbohydrate Intake on Body Fat and Metabolic Criteria in US College Students
Authors: Navrkal Brittany , Nelson Eric , Lofgren Ingrid , Melanson Kathleen
Published: June 2021

Indigestible, fermentable carbohydrates (IFCHO) are bioactive dietary carbohydrates not digested by human enzymes but are fermented into short chain fatty acids and gases by colonic bacteria. IFCHO display prebiotic effects and may influence body fat percent (BF%) and impact metabolic syndrome (MetS) criteria. Intake of an IFCHO subclass, oligosaccharides (OS), and OS subclasses fructans (FS) and galactooligosaccharides (GOS), have not been explored in the general US population. The purpose of this cross‐sectional study was to observe the effect of OS, FS and GOS intake on BF% and MetS criteria in US college students (n=151, BF%=23.7±9.0%, mean number of MetS criteria=0.8±0.9). Intake of OS, FS and GOS was quantified via the Comprehensive Nutrition Assessment Survey. BF% was measured via BodPod, blood lipids and blood glucose via Cholestech, waist circumference and blood pressure via standardized protocols. Median split was used to classify subjects with high and low intakes of OS, FS, and GOS and were analyzed via ANOVA. Subjects consuming less OS and GOS had higher BF% than those with higher intake (25.4±9.8 vs. 22.0±7.9%; p=.029 and 25.6±9.2 vs. 21.8±8.5%; p=.014 respectively). Subjects consuming less GOS had more MetS criteria compared to those with higher GOS intake (1.0±1.0 vs. 0.6±0.8 factors; p=.004). Significant difference in BF% and MetS criteria were not seen in high vs low FS intake. These results show that higher OS and GOS intake may impact BF% and MetS criteria in US college students. Randomized control trials are needed to further assess potential relationships.
6‐Gingerol Inhibits Lipid Accumulation and Obesity‐Induced Inflammatory Responses In 3T3‐L1 adipocytes and RAW264.7 Macrophages.
Authors: CHOI JIA , Seo Min Jung , Ryu SuJung , Hwang JiHyun , Jeon JeonHui , Lee YeonJoo , Koh EunJeoung , Lee BooYong
Published: June 2021

The obesity‐induced inflammatory response in adipocyte is characterized by an induced migration of macrophages. MCP‐1 and TNF‐α are important modulators of a lipid accumulation and obesity‐induced inflammation. 6‐gingerol has been known to inhibit pro‐inflammatory cytokines secretion from macrophages and abnormal lipid accumulation in adipocytes. Here we show that 6‐gingerol significantly decreased the mRNA expression levels of TNF‐α, aP2, C/EBPα and PPARγ in 3T3‐L1 adipocytes. Also, 6‐gingerol treatment of co‐cultured 3T3‐L1 adipocytes and RAW264.7 macrophages resulted in a decrease in NO production and cytokine expression of MCP‐1, TNF‐α, Interleukin 6 (IL‐6), interleukin‐1 beta (IL‐1β) which is related to inflammation, regulated upon activation interleukin 10 (IL‐10) which is related to anti‐inflammation. We expect that the 6‐gingerol may provide useful applications to reduce the lipid accumulation and obesity related chronic inflammatory properties.
Changes in Sodium Levels in Canadian Packaged Foods: 2010 to 2013
Authors: Arcand JoAnne , Jefferson Katherine , Schermel Alyssa , L'Abbe Mary
Published: June 2021

In 2010, Canada implemented a population‐wide sodium reduction strategy that included sodium reduction benchmarks for packaged foods; however, no evaluation of this policy has been conducted. This study measured changes to sodium levels in packaged foods contributing the most sodium to the Canadian diet. A database containing the nutrition information on 25,883 Canadian packaged foods available on the market in 2010 and 2013 was used (presented as means ± SD, mg/100g). The greatest reductions were observed in condiments (1309 ± 790 to 1048 ± 620; 19.9% reduction, p=0.005), breakfast cereals (375 ± 246 to 301 ± 242; 19.7% reduction, p=0.001), canned vegetables and legumes (269 ± 156 to 217 ± 180; 19.3% reduction, p<0.001), plain chips (462 ± 196 to 376 ± 198; 18.6% reduction, p=0.004, canned condensed soup (291 ± 62 to 250 ± 57; 14.1% reduction, p=0.003), sausages and wieners (912 ± 219 to 814 ± 195; 10.7% reduction, p=0.012), fresh and frozen meat and poultry (535 ± 228 to 496 ± 323; 7.3% reduction, p=0.001), and shelf‐stable mixed dishes (330 ± 114 to 308 ± 111; 6.7% reduction, p=0.002). Only 2 categories had higher sodium levels: oriental sauces (1355 ± 1345 to 3783 ± 2443; 179.2% increase, p<0.001), oriental noodles (222 ± 110 to 258 ± 79; 16.2%, p=0.025). Overall, there was a slight increase in the proportion of foods that met at least one of the sodium benchmark targets, from 51.4% of products in 2010 to 55.7% in 2013. This data shows that some progress has been made in reducing the sodium content of packaged foods, but that continual action by the food industry is still required. Funding: Canadian Institutes of Health Research
Prevalence and Characteristics of Written Nutrition Standards for Foods Served or Sold in Municipal Government Buildings or Worksites in the United States, 2014
Authors: Onufrak Stephen , Moore Latetia , Carlson Susan , Galuska Deborah
Published: June 2021

With over 10 million municipal employees across the U.S., establishing nutrition standards for foods sold in municipal government buildings is a potentially far‐reaching strategy to increase healthy food and beverage choices for employees and the public. We used data from a nationally representative 2014 CDC survey of 2232 U.S. municipalities to examine the prevalence of written nutrition standards among municipalities, whether standards addressed offering fruits and vegetables, whole grains, low‐calorie beverages, free drinking water or low‐fat dairy, limiting sodium or trans‐fat, or providing calorie labeling of items and whether standards applied to food served to employees, general population, or institutionalized persons. After excluding 219 municipalities with missing data or who responded “don't know”, 3.8% reported having written nutrition standards. Prevalence of nutrition standards differed by census region (p=0.002) and were most common in the West (6.7%) and least common in the Midwest (1.9%). Prevalence of nutrition standards differed by population size (p<0.0001), increasing from 2.1% among municipalities with <10,000 persons to 13.1% among municipalities with 蠅50,000 persons. Among those municipalities with standards, 70% applied to foods served to local government employees and 72% to those served to the general public. The most common objectives addressed in nutrition standards were offering fruits and vegetables, low‐calorie beverages, and free drinking water. Calorie labeling and limiting trans‐fat were addressed less frequently. In conclusion, few municipalities had written nutrition standards for foods served or sold in municipal government buildings or worksites in 2014.
Tree Nuts Improve Glycemic Control: A Systematic Review and Meta‐Analysis of Randomized Controlled Dietary Trials
Authors: Viguiliouk Effie , Kendall Cyril , Blanco Mejia Sonia , Cozma Adrian , Ha Vanessa , Mirrahimi Arash , Jayalath Viranda , Augustin Livia , Chiavaroli Laura , Leiter Lawrence , de Souza Russell , Jenkins David , Sievenpiper John
Published: June 2021

Background

Tree nut consumption is associated with reduced diabetes risk, however, results from randomized controlled trials (RCTs) on glycemia have been inconsistent.

Aim

We conducted a systematic review and meta‐analysis of RCTs to assess the effect of tree nuts on glycemic control.

Methods

We searched MEDLINE, EMBASE, CINAHL, and Cochrane databases through 8 August 2014 for relevant RCTs 蠅3‐weeks reporting HbA1c, fasting glucose (FBG), fasting insulin (FPI), and/or HOMA‐IR. Two independent reviewers extracted relevant data. Data were pooled using generic inverse variance random effects models and expressed as mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed (Cochran's Q) and quantified (I2).

Results

31 trials (n=1645) met the eligibility criteria. Diets emphasizing tree nuts significantly lowered FBG (MD=‐0.11 mmol/L, 95% CI:‐0.18, ‐0.03 mmol/L), FPI (MD=‐4.79 pmol/L, 95% CI:‐8.12, ‐1.46 pmol/L) and HOMA‐IR (MD=‐0.45, 95% CI:‐0.81, ‐0.09) compared with isocaloric control diets. No effects were observed for HbA1c, however the direction of effect favoured tree nuts.

Limitations

Majority of trials were of poor quality and short duration.

Conclusion

Pooled analyses show diets higher in tree nuts improve glycemic control. Longer, higher quality trials are needed.

Funding International Tree Nut Council Nutrition Research & Education Foundation
Physical Activity Between Menarche and First Pregnancy and Risk of Breast Cancer
Authors: Malik Vasanti , Liu Ying , Rosner Bernard , Cespedes Elizabeth , Sturgeon Kathleen , Joshi Amit , Tobias Deirdre
Published: June 2021

Background

A longer interval between age at menarche and 1st pregnancy is a known breast cancer risk factor. Whether physical activity during this period can mitigate cancer risk is unknown.
Methods. We analyzed 65569 parous women in the Nurses' Health Study II who reported their physical activity at ages 12 to 34 in 1997. Multivariable relative risks (RRs) were estimated using Cox proportional hazards regression.
Results. 2078 breast cancer cases occurred between 1989 and 2011. As expected, a longer interval between menarche and 1st pregnancy was associated with greater breast cancer risk (RR=1.04 per additional yr, 95% CI 1.03‐1.05); overall, this relationship did not vary by physical activity level before 1st pregnancy. However, an inverse association between physical activity before 1st pregnancy and breast cancer risk was observed for women with a menarche to 1st pregnancy interval of <10 yrs (RR=0.59 for highest vs lowest quartile of activity, 95% CI 0.39‐0.90), with no association in women with longer intervals.

Conclusion

Physical activity before 1st pregnancy did not modify the association between the interval from menarche to 1st pregnancy and breast cancer risk, except among women with an interval of <10 yrs, in which early physical activity was inversely associated with breast cancer risk.

Supported by: NIH U54 CA155626, CA155850, CA155496 and U01 CA116850
Neutrality in Nutrition Science: Perspectives for Effective Public‐Private Partnerships
Authors: Shlisky Julie , Beaudreault Amy , Wilkinson Lua , Mclean Mireille , Arabi Mandana
Published: June 2021

The multi‐disciplinary nature of nutrition science creates an opportunity to engage diverse partners from various scientific fields and institutions, including private industry. However, the variety of partnerships also produces the opportunity for competing personal and professional interests. Although neutrality is of concern in nutrition research, guidelines are not defined in the literature. This qualitative study aimed to identify perceived challenges to achieving neutrality in the nutrition space and emphasize measures to ensure integrity in nutrition research through the experiences of experts. In Spring 2014, one‐on‐one interviews (n = 17) were conducted among nutrition science professionals. Interviewees were selected for diversity in experience, nationality, age, gender, sector and country of employment and provided agreement of confidentiality. The semi‐structured interview guide was pilot‐tested (n = 2) to secure content validity. Commonly used terms to define neutrality included: lack of conflict of interest, objective, unbiased, and evidence‐based decision making. Key themes guided development of five principles for pursuing neutrality utilizing appropriate guidelines and procedures: 1) Independent programing, 2) Systematic peer‐review, 3) Sectorial and geographic diversity, 4) Transparency in the decision‐making process, and 5) Fundraising diversity. Though only an initial step in an under‐studied area, adoption of these principle‐guided strategies may promote successful collaboration among public‐private partnerships. Research was supported by The Sackler Institute for Nutrition Science at the New York Academy of Sciences.
High fat diet induced obesity is associated with increased abundance of pro‐inflammatory Lactobacillus in Peyer's patches of small intestine
Authors: Sun Jin , Qi Ce , Qiao Yi , Jiang Wei , Xiao Hang
Published: June 2021

We investigated the association between microbiome composition in peyer's patches in small intestine and high‐fat diet‐induced obesity in mice. C57L/6J male mice were fed either low fat (10% calories from fat, CT) or high fat (50% calories from fat) diets for 25 weeks, and the high‐fat diet‐fed mice were classified to obesity prone (OP) or obesity resistant (OR) based on their body weight gains. Microbiome was harvested from peyer's patches analyzed for bacterial composition. Our results showed that the numbers of peyer's patches inhabiting Lactobacillus were significantly lower in OP mice. Further selection of Lactobacillus generated 52, 18 and 22 isolates from CT, OP and OR mice, respectively. They belonged to 13 different phenotypes. Lactobacillus reuteri was the most abundant strain, but its abundance in OP mice was much lower. There were 8 subgroups of these L. reuteri. L. reuteri L3 and L. reuteri L8 were the specific strain found in CT and OP mice, respectively. Oxidative resistant Lactobacillus was much higher in high‐fat diet‐fed mice. Co‐cultured with peyer's patches cells, L8 induced higher production of pro‐inflammatory cytokine such as IL‐6, IL‐12 and TNF‐alpha, whereas, L3 induced higher production of anti‐inflammatory cytokine such as IL‐10. Overall, our results suggested that high‐fat diet may induce oxidative stress in small intestine that promotes the growth of pro‐inflammatory Lactobacillus strains with high resistance to oxidative stress, and these phenomena is specific for OP mice.
This work was supported by National Natural Science Foundation of China (No. 31201805).
Lingonberries have Anti‐obesity Effects and Modulate the Gut Microbiota in High‐fat Fed C57BL/6J Mice
Authors: Heyman‐Lindén Lovisa , Kotowska D , Sand E , Holm C , Fåk F , Berger K
Published: June 2021

This study aimed to investigate if the ability of lingonberries to prevent diet‐induced obesity is associated with an altered gut microbiota. Furthermore, two different batches of lingonberries were tested.

C57BL/6J mice were fed high‐fat (HF) diet (control) or HF diet supplemented with lingonberries (20% w/w) from two different batches (Lingon1 and Lingon2) for 11 weeks. The composition of cecal gut microbiota was assessed by 16S rRNA gene sequencing (MiSeq, Illumina). Lingonberry intake was found to prevent weight gain, hepatic steatosis and other metabolic parameters associated with obesity. However, these effects were more prominent in mice fed HF diet supplemented with Lingon1, compared to Lingon2. Interestingly, both lingonberry batches reduced the plasma levels of lipopolysaccharide binding protein and the inflammatory marker serum amyloid A (SAA). Lingonberry intake significantly increased beta diversity of cecum microbiota and positively correlated with the abundance of Akkermansia spp. The relative abundance of Parabacteroides spp negatively correlated with SAA, and tended to be reduced in the microbiota of mice receiving Lingon1.

We conclude that lingonberries exert anti‐obesity effects when supplemented to a HF diet in mice, but the magnitude varies depending on which batch of berries is used. Regardless of the berry source, lingonberries promote changes of gut microbiota and lower endotoxemia and low‐grade inflammation in mice. Further discerning the microbiota of mice receiving lingonberries may provide additional knowledge to correlate changes in gut microbiota with protection against obesity.

Supported by: Lund University Antidiabetic Food Centre, a VINNOVA Excellence Center.
Low Serum Sphingolipids in Attention Deficit Hyperactivity Disorder (ADHD)
Authors: Henríquez‐Henríquez Marcela , Solari Sandra , Allende Fidel , Quiroga Teresa , Kim Benjamin , Deckelbaum Richard , Worgall Tilla
Published: June 2021

Background

ADHD is the most prevalent neurodevelopmental disorder in children and has been associated with a lag in neuronal maturation. Sphingolipids are essential for myelination, neuronal function and development. We hypothesized that serum sphingolipid profiles are different in ADHD.

Objective

To characterize the serum sphingolipid profile in ADHD patients and two independent control groups: non‐affected relatives and non‐affected subjects without family history of ADHD.

Method

Sphingolipid profiles were determined by mass spectrometry in 77 participants (28 ADHD, 28 related controls and 21 unrelated controls). Diagnosis was based on the criteria of Diagnostic and Statistical Manual of Mental Disorders (DSM IV‐TR). Groups were compared by parametrical statistics.

Results

All major sphingomyelins (C16:0, C18:0, C18:1 and C24:1), ceramide C24:0 and deoxyceramide C24:1 were significantly decreased in ADHD at relative reductions between 20‐30%. In our sample, decreased serum sphingomyelin levels distinguished ADHD patients with 79% sensitivity, 78% specificity and an estimated negative predictive value of 97%.

Conclusion

Serum sphingomyelin and select ceramides are decreased in ADHD patients. Longitudinal studies are required to evaluate if these findings reflect an ADHD specific pathomechanisms. Low serum sphingomyelins levels are a potential biomarker for ADHD.

Grant support: None
Calcium Supplementation for Preeclampsia Prevention: Estimated Risk of Excessive Intake in Ethiopian Women
Authors: Tesfaye Biniyam , Wuehler Sara , Baye Kaleab , De‐Regil Luz , Moges Tibebu , Adish Abdulaziz , Dickin Katherine
Published: June 2021

The WHO recommends supplementation with 1.5–2.0 g/d elemental calcium (Ca) for pregnant women in settings with low dietary Ca intake, to help prevent preeclampsia. There is insufficient guidance on implementing this recommendation and avoiding risk of excessive Ca intake at the population level. We investigated usual dietary Ca intake of Ethiopian women of childbearing age and simulated the impact of different supplementation doses. In a nationally‐representative sample (n= 7834), 24‐hr dietary recall data was analyzed to estimate usual dietary Ca intake and the proportions of women below the estimated average requirement (EAR ) or above the upper tolerable limit (UL) at different supplementation dosages. An EAR of 1.1 and 0.8 g/d and UL of 3.0 and 2.5 g/d was used for women 15‐18 and 19‐45 y, respectively. Mean Ca intake was 506.4 mg/d ± 263.6; 96.6% of women 15‐18y and 88.4% overall had inadequate intake. In simulations, supplementing with 1.0, 1.5, and 2.0 g/d would allow >99% of women to meet the EAR. The 1.5 and 2.0 g/d supplemental doses would result in intakes above the UL in 4.9% and 38.4% of all women, respectively. At 1.5g/d, only 0.6% of women aged 15‐18y would exceed the UL. At the 1.0g/d dose of Ca, the overall prevalence of excessive intake would be below the target of 2.5% (0.74%). Thus, with high adherence, a lower dose of 1.0 g/d would allow >99 % of Ethiopian women meet the EAR and could be safer than the recommended 1.5‐2.0 g/d. Similar investigation of potential risks of Ca supplementation using 1.5‐2.0 g/d is warranted in countries considering this intervention. Funded by The Micronutrient Initiative.
Anemia Prevalence May Be Reduced Among Countries that Fortify Flour
Authors: Pachon Helena , Barkley Jonathan , Wheeler Kathleen
Published: June 2021

The effectiveness of flour fortification in reducing anemia prevalence is equivocal. The goal of this study was to utilize existing national‐level data to assess whether anemia in non‐pregnant women was reduced after countries began fortifying wheat flour, alone or in combination with maize flour, with at least iron, vitamin A, vitamin B9 or vitamin B12. Nationally representative anemia data were identified through DHS reports, the WHO‐VMNIS database, and other surveys. Countries with at least 2 anemia surveys were considered for inclusion. Within countries, surveys were excluded if data were not available for non‐pregnant women, if altitude was not consistently adjusted for, or if the blood‐draw site (e.g., capillary or venous) or hemoglobin‐quantification method (e.g., HemoCue or Cyanmethaemoglobin) differed. Anemia prevalence was modeled for countries that had pre‐ and post‐fortification data (n=12) and for countries that never fortified flour (n=20) using logistic regression models that controlled for time effects, human development index (HDI), and endemic malaria. After adjusting for HDI and malaria, each year of flour fortification was associated with a 2.4% reduction in the odds of anemia prevalence (PR=0.976, 95%CI: 0.975, 0.978). Among countries that never fortified, no reduction in the odds of anemia prevalence over time was observed (PR=0.999, 95%CI: 0.997, 1.002). Although this type of evidence precludes a definitive conclusion, available evidence from national‐level surveys suggests that after controlling for time effects, HDI, and endemic malaria, anemia prevalence has decreased significantly in countries that fortify flour with micronutrients, while remaining unchanged in countries that do not. Funding: Emory, FFI.
Oat Avenanthramides Induce Heme Oxygengase‐1 Expression via Nrf2‐mediated Signaling in HK‐2 Cells
Authors: Sang Shengmin , Fu Junsheng , Zhu Yingdong , Yerke Aaron , Wise Mitchell , Johnson Jodee , Chu YiFang
Published: June 2021

Laboratory and human studies have shown that avenanthramides (AVAs), unique compounds found in oats, are strong antioxidants. However, their specific mechanism of action remains unclear. The objective was to investigate the abilities of the three major AVAs in oats (2c, 2p, 2f) to activate Nrf2 nuclear translocation leading to the activation of phase II detoxification genes in vitro. The three AVAs significantly increased heme oxygenase‐1 (HO‐1) expression in HK‐2 cells in both a dose‐ and time‐dependent manner. Mechanistic studies show that HO‐1 expression induced by AVAs is mediated via Nrf2 translocation. All three AVAs stimulated Nrf2 nuclear translocation in both a dose‐ and time‐dependent manner. The addition of N‐acetylcysteine (NAC) suppressed the HO‐1 expression induced by 2c, 2f, and 2p, establishing that ROS plays a role on the up‐regulation of HO‐1 by AVAs. Pretreatment of cells with inhibitors of p38, PI3K, and MEK1 did not attenuate AVA‐induced HO‐1 expression, suggesting that HO‐1 expression is not associated with PI3K or MAPK activation. Hydrogenation of the double bond of the functional α,β‐unsaturated carbonyl group of AVAs eliminated their effects on HO‐1 expression, suggesting a role for the functional α,β‐unsaturated carbonyl group in the mechanism of action of AVAs. These results show the ability of AVAs to induce HO‐1 expression in HK‐2 cells. This action appears to be mediated by Nrf2 activation and is not associated with PI3K or MAPK activation.