bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the Primate “Squeeze‐back” Swallowing Mechanism using X‐ray Reconstruction of Moving Morphology and Fluoromicrometry
Authors: Orsbon Courtney P , Gidmark Nicholas J , Ross Callum F 
Published: June 2021

The primate hyolingual apparatus is a complex composite of a muscular hydrostat and a floating bone that is essential for feeding. In particular, the characteristic elevation (i.e., the “squeeze‐back” mechanism) and retraction of the tongue base during swallowing may be important in flipping the epiglottis to protect the laryngeal inlet. However, the link between hyolingual muscle behavior and hyolingual kinematics is poorly supported by in vivo data. Tongue base elevation and retraction could be due to one or a combination of three mechanisms thanks to its redundant morphology: intrinsic tongue muscles inducing hydrostatic deformation, extrinsic muscles moving the whole tongue, or hyoid elevation and protraction deforming the tongue. We evaluated these possibilities using a macaque model system. We implanted two rhesus macaques (one male, one female) with tantalum beads and filmed them during feeding using biplanar videofluoroscopy for X‐ray Reconstruction of Moving Morphology and fluoromicrometry workflows to measure hyoid kinematics, tongue deformation, and muscle length change with high spatiotemporal resolution. The results of general linear models demonstrate significant effects of hyoid movement and hydrostatic deformation on tongue base elevation, while all three mechanisms predict tongue base retraction (p < 0.001). Future directions include incorporating electromyography to understand how hyolingual muscle activity, especially active shortening, generates to tongue movement. These findings not only give insight into the biomechanics of the hyolingual apparatus, but they are also relevant for dysphagia rehabilitation as they suggest that more muscles are involved in tongue base retraction‐‐and perhaps epiglottic flipping‐‐than previously thought.Support or Funding InformationThis research was supported by the NIH (R01 DE023816‐03 and T32 HD007009‐41) and the NSF (MRI 1338066).
Incorporation of Dietary n‐3 Fatty Acids into Selective Phosphatidylcholine Lipids in Human Plasma after Salmon Intake
Authors: Zacek Petr , Bukowski Michael , Raatz Susan , Picklo Matthew 
Published: June 2021

Elevated intake of n‐3 long chain polyunsaturatedfatty acids (n‐3 LCPUFA) is associated with reduced risk for cardiovascular disease. Intake of n‐3 LCPUFA is often quantified by analysis of plasmaphospholipid fatty acids (PLFA); however, the typical analysis by gaschromatography does not allow for determination of the phospholipid species that are enriched by the n‐3 LCPUFA. In this work, we tested the hypothesis that the n‐3 LCPUFA, namely docosahexaenoic acid (DHA) and eicosapentaenoic acid(EPA), are incorporated into select phosphatidylcholine (PC) species following intake of farm‐raised, Atlantic salmon. Plasma samples were obtained from a randomized, cross‐over designed study in which participants (n = 9) consumed farm‐raised Atlantic salmon at levels of 90 g and 180 g twice weekly for 4 weeks with an 8 week washout between treatments. Plasma lipids were extracted and analyzed using a shotgun MS/MS method with the capability to quantify isobaric PC species. Our data indicate that under basal conditions, EPA and DHA are incorporated into PC species containing palmitic acid (PA), stearic acid (SA), and oleic acid (OA) as the complementary fatty acid in the concentration order of PA>SA>OA. EPA content was enriched in PA, SA, and OA species following salmon intake whereas only PA and SA containing DHA species were elevated following intake. Interestingly, PCs containing docosapentaenoic acid (DPA) were not elevated even though the salmon contained DPA. PC species containing n‐6 PUFA demonstrated a similar pattern of PA>SA>OA as the complementary fatty acids. No changes in n‐6 containing PC species occurred following salmon intake. Although linoleic acid (LA) was highly enriched in total PC, LA was not detected as a complementary fatty acid to any n‐3 LCPUFA species and was a minority complementary species for other n‐6 PUFA. In conclusion, our data demonstrate that (1)n‐3 LCPUFA incorporate into selective PC pools some of which increase with dietary n‐3 LCPUFA intake, and (2) there exists a hierarchy of PUFA containing PC species with selectivity for lower carbon length and higher saturation level for the complementary fatty acid. These data allow for a more refined characterization of biomarkers for PUFA intake and understanding of PC biochemistry in humans.Support or Funding InformationThis work was supported by National Institute of Food and Agriculture, U.S. Department of Agriculture, under award number 2014‐67017‐21758 and through USDA‐ARS project 5450‐51000‐048‐00D.
Consumption of the total Western diet (TWD) enhanced and sustained colonic inflammation and promoted colon tumorigenesis in mice, which led to marked changes in the composition of the gut microbiome in mice
Authors: Benninghoff Abby , Hunter Ashli , Monsanto Stephany , Phatak Sumira , Hintze Korry , Ward Robert , Lefevre Michael 
Published: June 2021

To improve translation of preclinical rodent nutrition studies to human trials, our research team developed the new Total Western Diet (TWD) for rodents with energy and nutrient profiles that emulate a typical Western diet. A series of pre‐clinical studies was preformed using different models of colon cancer to compare TWD to the AIN93G diet, a standard basal diet designed to promote animal health. Consumption of TWD 1) increased number of aberrant crypt foci in A/J mice initiated with azoxymethane (AOM), 2) significantly enhanced tumorigenesis in C57BL/6J mice initiated with AOM and provided dextran sodium sulfate (DSS) to promote colonic inflammation and 3) enhanced colon tumorigenesis in APCMin/+ mice provided DSS. Using the AOM/DSS model of CAC, we assessed the impact of TWD on the colitis disease activity index, colon tissue histopathology and composition of the gut microbiome by 16S sequencing over the course of disease development (pre‐initiation, colitis, recovery and terminal). We determined that TWD consumption markedly enhanced colitis activity (40‐fold increase) compared to mice fed AIN93G. Moreover, TWD‐fed mice had significantly higher histopathology scores for inflammation and mucosal injury during the period of colitis and, importantly, during the recovery phase of this disease model. Colonic inflammation in TWD‐fed mice persisted to the end of the study (day 105), whereas mucosal injury (save for sites of neoplasia) had resolved. Prior to initiation with AOM/DSS, the gut microbiome compositions of AIN93G‐ and TWD‐fed mice were very similar. As colitis progressed, the populations became more distinct, especially so by the recovery stage (day 45), which was also typified by sustained colonic inflammation and mucosal injury in TWD‐fed mice. By the study end (day 105), separation between the fecal microbiomes for the different diet groups was evident. Finally, examination of the terminal fecal microbiome revealed distinct gut microbiota profiles for TWD‐fed animals initiated with AOM/DSS compared to sham mice, whereas a distinction was not evident for those fed AIN93G. Collectively, these data show that the TWD markedly enhanced colorectal tumorigenesis in repeated experiments and multiple animal models. Moreover, enhanced and sustained inflammation of the colon epithelium is a probable mechanism for promotion of CAC by TWD. Finally, mice with pronounced colitis‐associated colorectal cancer, induced by dietary exposure to TWD, harbored microbiomes distinct from their counterparts fed healthy diets.Support or Funding InformationUtah Agricultural Experiment Station, Project UTA‐1178; USDA NIFA/AFRI Grant No. 2014‐67017‐21755
Aberrant crypt formation accompanies an increase of opportunistic pathogens/bacteria in the inflammatory gut of C57BL/6 mice fed a high‐fat diet
Authors: Zeng Huawei , Ishaq Suzanne L , Liu Zhenhua , Keehr Kay A , Bukowski Michael R 
Published: June 2021

Obesity and high fat diet are risk factors for colon cancer, but the mechanism of this relationship remains to be determined. We tested the hypothesis that a high fat diet promotes the formation of aberrant crypt foci (ACF, preneoplastic lesions) in a manner associated with changes in hindgut bacterial taxa. We examined the susceptibility to azoxymethane (AOM)‐induced colonic ACF and microbiome composition in C57/BL6 mice fed a low fat (LF, 10% energy fat) diet or a high fat (HF, 45% energy fat) diet for 11 weeks. Mice receiving the HF diet exhibited increased plasma leptin, body weight, body fat composition and inflammatory cell infiltration in the ileum compared with those in the LF group. Consistent with a gut inflammatory phenotype, we observed an increase in colonic ACF, plasma interleukin 6 (IL6), tumor necrosis factor α (TNF α), monocyte chemoattractant protein 1 (MCP1), and inducible nitric oxide synthase protein in the ileum of the HF‐AOM group compared with those in the LF‐AOM group. Fecal DNA was extracted and 16S universal eubacterial primers were utilized to determine the microbiome composition using an amplicon pyrosequencing method. Although the HF and LF groups did not differ in bacterial alpha‐diversity, the HF and LF diets resulted in unique bacterial community structures in the hindgut. When treated with AOM, the abundance of certain short chain fatty acid (SCFA) producing bacteria (e.g., Barnesiella) and the amount of fecal SCFA (e.g., acetic acid) were lower in the HF group compared with those in the LF group. Furthermore, we identified a high abundance of Anaeroplasma bacteria (opportunistic pathogens), accompanied with ACF formation in the HF group. Taken together, we demonstrate that HF feeding promotes ACF formation associated with an increase of opportunistic pathogens / bacteria in the hindgut of C57BL/6 mice.Support or Funding InformationThis work was funded by the US Department of Agriculture, Agricultural Research Service, Research Project 3062‐51000‐050‐00D.
Changes in body adiposity and its associated inflammation affect metastasis of Lewis lung carcinoma in mice
Authors: Yan Lin , Sundaram Sneha 
Published: June 2021

A hallmark of obesity is the increase in body adiposity and its associated inflammation that contribute to obesity‐related chronic diseases including cancer. Clinical studies show that obesity is related to poor prognosis, early recurrence and metastasis in cancer patients. Recurrence and metastasis are the most devastating aspects of cancer. We studied roles of changes in body adiposity (induced by changes in diet formulation or feeding method) in spontaneous metastasis of Lewis lung carcinoma in mice. Compared to the AIN93G control diet (16% of energy from corn oil), the high‐fat diet (45% of energy from coil oil) significantly increases body fat mass and plasma concentrations of proinflammatory cytokines [e.g. monocyte chemotactic protein‐1 (MCP‐1) and plasminogen activator inhibitor‐1 (PAI‐1)] and significantly increases the extent of metastasis, evidenced by increases in number and size of metastases formed in lungs. A restriction in high‐fat diet intake by 5%, which maintains the body adiposity and plasma MCP‐1 and PAI‐1 levels similar to mice fed the AIN93G diet, significantly reduces lung metastasis compared to unrestricted feeding of the high‐fat diet. Knocking out MCP‐1 or PAI‐1 from mice significantly reduces high‐fat diet‐enhanced metastasis. The metastatic enhancement was not observed in mice fed a 45% high‐sucrose diet, which did not elevate body adiposity and proinflammatory cytokines compared to a 45% high‐fat diet. Furthermore, we found from a feeding study that there are no differences in proinflammatory cytokines (including MCP‐1 and PAI‐1) in mice fed high‐fat diets containing oils with different amounts of n3 and n6 fatty acids. Our results indicate that increases in adiposity and its associated proinflammatory cytokines may contribute to the high‐fat diet‐enhanced metastasis and that sources of dietary energy, rather than the energy itself, may lead to differences in metastatic aggression of Lewis lung carcinoma.Support or Funding InformationThe U.S. Department of Agriculture, ARS, research project 5450‐51000‐045‐00D.
The influence of genetic ablation of tumor necrosis factor‐α on the colonic Wnt pathway cascade under an obese state
Authors: Liu Zhenhua , Li Jinchao , Frederick Armina‐Lyn M. , Jin Yu , Xu Xiaolin , Wood Richard J. 
Published: June 2021

Obesity is an established risk factor for colorectal cancer (CRC), but the mechanism(s) responsible for this relationship are still not fully understood. We hypothesize that obesity creates a low‐grade colonic inflammatory microenvironment, which facilitates the development of CRC. Our prior study suggested tumor necrosis factor alpha (TNF‐α) might elevate the Wnt‐signaling, and thereby promote the colonic tumorigenesis. In the present study, we observed that several colonic inflammatory cytokines (TNF‐α, IL‐1β, IFNg) and Wnt pathway specific genes (e.g. Axin2) were upregulated in an obese state (p < 0.05), whereas the genetic ablation of TNF‐α suppressed the elevation of Wnt‐signaling induced by dietary obesity, as indicated by decreased levels of phopho‐GSK3β, and active β‐Catenin (p < 0.05), two key components in Wnt pathway cascade. A Wnt pathway specific gene expression profiling further demonstrated that the genetic abolishment of TNF‐α attenuated aberrations of several genes within the colonic Wnt pathway cascade including the over‐expressed Axin2, a readout of the Wnt pathway (p < 0.05). Colonic epithelial proliferation (Ki‐67), which is partially under the control of Wnt signaling, was also decreased by the blockade of TNF‐in obese mice (p < 0.05). These results indicate that obesity‐driven inflammation plays a role in the regulation of the tumorigenic Wnt‐signaling pathway, which contributes to the development of obesity‐associated CRC.Support or Funding InformationSupported in part by a USDA/NIFA grant, a USDA/Hatch grant and a HNRCA competitive intramural pilot grant to ZL
Green Tea Extract Protects Against Diethylnitrosamine‐Mediated Liver Injury And Cell Proliferation By Attenuating STAT3 And iNOS Expression In High Fat‐Induced Obese Mice With Nonalcoholic Steatohepatitis
Authors: Kim Joshua B , Li Jinhui , Chitchumroonchokchai Chureeporn , Sasaki Geoffrey Y , Thomas‐Ahner Jennifer M , Clinton Steven K , Bruno Richard S 
Published: June 2021

Nonalcoholic steatohepatitis (NASH) increases hepatocellular carcinoma (HCC) risk by increasing inflammation and oncogenesis. Antiinflammatory activities of green tea extract (GTE) protect against dietary high‐fat (HF)‐induced NASH. We hypothesized that the hepatoprotective antiinflammatory activities of GTE during NASH would also prevent diethylnitrosamine (DEN)‐induced progression towards HCC. Male C57BL/6J mice (4 wk old) were fed a HF diet devoid of, or supplemented with, GTE at 2% (w/w) and received once weekly intraperitoneal injections of saline vehicle or DEN (60 mg/kg; wk 5 and 7) until 25 wk old prior to assessing NASH, inflammation, and oncogenic responses. DEN did not (P>0.05) exacerbate liver steatosis, hepatocyte ballooning, or mRNA expression of TNFα and MCP‐1 compared with saline‐treated mice. However, GTE protected against (P<0.05) histologic evidence of NASH and TNFα and MCP‐1 expression to a similar extent in saline‐ and DEN‐injected controls. GTE inhibited DEN‐induced increases in serum alanine aminotransferase (ALT) activity and iNOS mRNA expression, which were not different from the lowered levels observed in saline‐treated mice fed GTE. GTE also similarly inhibited DEN‐induced increases in signal transducer and activator of transcription 3 (STAT3) protein expression to levels not different from those lowered by GTE in saline‐treated mice. GTE attenuated positive staining towards hepatocyte proliferating cell nuclear antigen (PCNA) that was otherwise exacerbated by DEN. Serum ALT was correlated (r = 0.74–0.83; P<0.0001) with iNOS, STAT3, and PCNA. Likewise, iNOS correlated with both PCNA and STAT3 (r = 0.64–0.65; P<0.05), suggesting that iNOS‐induced inflammation centrally regulates liver injury and oncogenic cell proliferation. GTE protects against DEN‐exacerbated STAT3/iNOS‐mediated oncogenic responses that otherwise provoke liver injury and cell proliferation.Support or Funding InformationSupported by USDA‐NIFA and OSU Comprehensive Cancer Center.
Interactive effects of blueberry supplementation and GPR109A deletion on gut microbiome profiles in mice
Authors: Shankar Kartik , Ying Zhong , Oksana Lazarenko P , Chintapalli Sree V , Chen Jin‐Ran , Wankhade Umesh D 
Published: June 2021

Blueberry‐supplemented (BB) diets in rodent models have shown to improve skeletal mass, glucose tolerance and endothelial function. In addition to the bioactive and dietary fibre components of these diets, effects of blueberries may be in part via modulation and action of the gut microbiome. However, few studies have characterized gut microbiome composition following BB supplementation. Since phenolic acids and gut microbiota‐derived short‐chain fatty acids (SCFAs) such as butyrate can bind and activate GPR109A (nicotinic acid receptor) signaling, we examined the interactive roles of GPR109A and BB‐supplementation on microbiome profiles in mice. Male GPR109A global knockouts and WT littermates were fed control or BB‐supplemented diets (5% w/w) for 4 weeks (n=10). All diets were based on the AIN‐93G formulation and contained 19% calories from protein, 17% from fat and 64% from carbohydrates. Body weight, body composition (non‐invasively via Echo MRI) and food intake were measured weekly and did not differ between groups within the study period. At the end of 4 wk serum, liver, adipose tissue depots and cecal contents were collected for further analysis. Microbial community profiling was conducted by sequencing the 16S rRNA (V4 region) followed by analysis using QIIME. BB‐diet fed mice showed greater a‐diversity (OTU richness) in both WT and GPR109A‐KO. Interestingly, GPR109A loss per se was associated with significantly lower a‐diversity relative to WT mice (p<0.05). Principal coordinate analysis of b‐diversity values showed highly significant effects of both genotype and diet (p<0.00001). BB diets affected abundance of 15 genera in WT mice, of which only 5 genera were also affected in GRP109A KO with BB‐treatment (p<0.05, two‐way ANOVA). However, BB diets in GPR109A KO altered 7 genera uniquely suggesting significant genotype‐diet interactions. Two‐way ANOVA analysis showed BB‐diets increased Bacteroidetes and decreased Firmicutes phyla (p<0.001) in both WT and KO mice. OTU abundance of genera including Facklamia, Clostridium, Coprococcus, Dorea, and Ruminoccous was affected by both diet and genotype of mice (p<0.01). LEfSE analysis confirmed enrichment of phyla Bacteroidetes with BB‐diets. Predictive functional metagenomics analysis using PiCRUST identified alterations of pathways involving immune and bacterial response, protein digestion, amino acid metabolism and xenobiotics biodegradation to be affected by genotype and BB‐diet. Associations between alterations in microbial abundance and diet‐associated changes in adipose tissue and liver gene expression will also be presented. Overall, these results suggest changes in microbial community structure with BB‐diets and also reveal novel host genotype dependent alterations in the microbiome. Support USDA CRIS 6206‐51000‐010‐05SSupport or Funding InformationSupport USDA CRIS 6206‐51000‐010‐05S
Extension‐Delivered Diabetes Program for Rural‐residing Latinos Improves Diabetes Self‐management, Self‐efficacy and Knowledge
Authors: Francis Sarah L , Keane Michelle 
Published: June 2021

Rural‐residing Latinos are at high diabetes risk due to limited access to healthcare services, high rates of overweight and obesity, and acculturation. Culturally‐sensitive diabetes self‐management education programs are needed to reduce the risk and severity of Type 2 diabetes among rural‐residing Latinos. Improvements in diabetes‐related self‐efficacy and knowledge can lead to improved diabetes self‐management outcomes. Latinos Living Well (LLW) was created using the Social Marketing Theory (SMT) and the Health Belief Model (HBM). SMT ensured the content was audience‐centered and culturally‐relevant. HBM constructs were addressed through facilitative discussion, cooking practicums, and hands‐on activities. LLW is made up of four two‐hour classes with culturally‐relevant food and physical activity examples, were taught in Spanish, and delivered through Cooperative Extension. This study evaluated the impact of LLW on diabetes self‐management practices, diabetes self‐efficacy, and diabetes knowledge. A convenience sample of rural‐residing Latino adults age 18+ in a Midwest state (n=120) were recruited, regardless of diabetes status, through collaborations with established community groups serving Latinos, radio commercials and print media, and word of mouth; 76 completed the program (63.3% completion rate). Participants completed a Spanish questionnaire comprised of validated tools, sociodemographic questions, and questions regarding diabetes status at the start of Class 1 (PRE) and the end of Class 4 (POST). Descriptive statistics analyzed sociodemographic data while paired‐samples t‐tests examined changes in diabetes self‐management, diabetes self‐efficacy and diabetes knowledge from PRE to POST. The majority were females (n=73; 97.3%), between the ages of 30 and 49 years (n=34; 51.6%), who were first generation immigrants (n=63; 87.5%). Two‐thirds (n=49; 65.3%) reported some history of a diabetes diagnosis. Significant increases were detected for diabetes self‐management practices (p<0.006), diabetes self‐efficacy (p<0.0001), and diabetes knowledge (p<0.004). These results suggest LLW is effective in improving diabetes self‐management practices, diabetes self‐efficacy, and diabetes knowledge outcomes among rural‐residing Latinos.Support or Funding InformationThis research was funded by the United States Department of Agriculture, National Institute of Food and Agriculture Rural Health and Safety Education Grant, #2014‐46100‐22349
Dietary genistein inhibits methylglyoxal‐induced advanced glycation end products formation in high‐fat diet‐fed mice
Authors: Zhao Yantao , Wang Pei , Sang Shengmin 
Published: June 2021

The formation and accumulation of advanced glycation end products (AGEs) was considered as a major pathogenic link between hyperglycemia and diabetes‐related complications. Methylglyoxal (MGO), as an important precursor of AGEs, circulates at high concentration in diabetic patients's blood and is linked to the development of diabetes chronic complications. In the present study, we investigated whether long‐term treatment of MGO plus high‐fat diet can cause accumulation of protein glycation in mice and whether dietary genistein can prevent the formation of AGEs and ameliorate high‐fat plus MGO induced metabolic syndrome. Our results indicate that chronic high‐fat plus MGO administration (0.12–0.2% in drinking water for 18 weeks) significantly elevates the levels of MGO and AGEs in mouse plasma, liver and kidney, and cause fatty liver. Dietary genistein treatment (0.067% and 0.2% in high‐fat diet) significantly ameliorates high‐fat plus MGO‐induced fatty liver and metabolic syndrome, such as lowering body weight gain, plasma levels of glucose, cholesterol, aspartate transaminase (AST), alanine transaminase (ALT), and liver triglyceride levels. Moreover, genistein administration also significantly decreases the levels of MGO and AGEs. Further mechanistic studies demonstrate that genistein could trap MGO in mice to form mono‐MGO‐genistein adduct. In addition, genistein could regulate expressions of glyoxalase I and II, and both catalytic and modifier subunits of glutamate‐cystein ligase to promote the detoxification of MGO. Furthermore, genistein down‐regulates the expression of the receptor of AGEs (RAGE) to inhibit the AGEs‐RAGE pathway.Support or Funding InformationThis work was supported by USDA‐NIFA grants 2012‐38821‐20012.