bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations Between Biomarker‐Calibrated Protein Intake and Bone Health in the Women's Health Initiative
Authors: Beasley Jeannette M , Larson Joseph , LaCroix Andrea Z , Neuhouser Marian L , Tinker Lesley F , Jackson Rebecca , Huang Ying , Snetselaar Linda , Eaton Charles , Prentice Ross L 
Published: June 2021

OBJECTIVEThe effects of dietary protein intake on bone health are controversial. This study examined the relation between protein intake with bone mineral density (BMD) and fracture within the Women's Health Initiative (WHI).METHODSThe WHI recruited 161,806 women aged 65–79 into the WHI‐Observational Study (OS) and WHI‐Clinical Trial (CT) between 1993 and 1998. Fractures were collected annually (WHI‐OS) or semi‐annually (WHI‐CT) by questionnaire through 2011. BMD was measured at baseline and 6 years among 10,833 women using dual‐energy x‐ray absorptiometry. Protein and energy intake were assessed via the WHI Food Frequency Questionnaire and calibrated using regression equations established based on biomarkers of protein and energy intake. Cox (fracture) and linear (BMD) regression models were adjusted for confounders including age, race/ethnicity, and body mass index.RESULTSMedian calibrated protein intake was 14% of energy. Women consuming 20% higher calibrated protein were 9% less likely to have a hip fracture (95% CI= 1%‐15%). Each 20% increase in calibrated protein was associated with higher BMD for total body (mean 6‐year change 0.004 g/cm2, 95% CI = 0.001–0.007 g/cm2) and hip (0.003 g/cm2, 95% CI= 0.001–0.005 g/cm2).CONCLUSIONHigher protein intake was associated with reduced risk of hip fracture and better maintenance of BMD over time. These data suggest higher protein intake may be an intervention target for preserving bone health.Funded by NHLBI (WHI) and NIA (4R00AG035002).
Molecular Chaperones in Cellular Protein Folding: Mechanisms and Pathways
Authors: Hartl Franz Ulrich 
Published: June 2021

The past two decades have witnessed a paradigm shift in our understanding of protein folding in the cell. While the three‐dimensional structures of functional proteins are determined by their amino acid sequences, it has become clear that in the crowded cellular environment many proteins depend on molecular chaperones to fold efficiently and at a biologically relevant time scale. Assistance of protein folding is provided by different types of chaperone which act to prevent misfolding and aggregation, often in an ATP‐dependent mechanism. In the cytosol, nascent chain‐binding chaperones, including Trigger factor and Hsp70, stabilize elongating polypeptide chains on ribosomes in a non‐aggregated state. Folding is then achieved either on controlled chain release from these factors or following polypeptide transfer to downstream chaperones, such as the cylindrical chaperonins, GroEL and TRiC. The latter provide nano‐compartments for single protein molecules to fold in isolation, unimpaired by aggregation.Once folded, many proteins continue to require chaperones to retain their functional state, particularly under conditions of cell stress. Failure of the chaperone network to maintain proteostasis, i.e. the conformational integrity of the cellular proteome, may facilitate the manifestation of pathological states, such as Parkinson's and Huntington's disease, in which proteins misfold and are deposited as aggregates. A decline in proteostasis capacity occurs during aging, presumably explaining why age is a major risk factor of neurodegeneration.I will discuss recent findings from mechanistic and systems‐level studies to understand the organisation of the cellular chaperone network.
Science Outreach at Washington University in St. Louis: The Young Scientist Program
Authors: Bradley Michael John , Siebrasse Erica , Mosher Jennifer , Woolsey Thomas 
Published: June 2021

The Young Scientist Program (YSP) is run by graduate and medical students and aims to improve science education in local schools, attract students to scientific careers, and increase the participation of underrepresented groups in science. YSP has developed several programs to reach St. Louis area students and teachers.Teaching TeamsYSP develops and leads inquiry‐driven science modules in local science classes covering a variety of scientific topics. Modules are modified with teacher input to integrate classroom curricula and state standards. Teaching teams have impacted >;7000 students since 1993.Summer FocusYSP places local high school students in laboratory internships. Each participant completes an independent research project with a graduate or postdoctoral mentor, and writes a research paper during the eight‐week internship. More than 250 local students have participated in Summer Focus.Teacher and Researcher PartnershipYSP provides summer research and curriculum enrichment experiences for public school teachers. Participants work with mentors on individual research projects and on development of modules for their classrooms.Benefits and OutcomesVolunteers gain a variety of skills not formally taught during graduate training. Student and teacher participants report increased interest in and understanding of scientific concepts.
Role of LDL receptor in the uptake of beta‐carotene by murine placenta and the embryo
Authors: Shete Varsha , Costabile Brianna , Quadro Loredana 
Published: June 2021

Beta‐carotene (bC) is the most abundant precursor of vitamin A in the human diet. Vitamin A derived retinoids are essential for normal embryonic development. Uptake of intact bC followed by local de novo biosynthesis of retinoids by cleavage of bC can be an important source of retinoids during embryonic development. Intact bC is circulated in association with various lipoprotein particles, especially apoE/apoB containing lipoproteins such as chylomicrons, VLDL and LDL.Potential role of LDL receptor (LDLr) in the uptake of supplemented bC by maternal and developing tissues was investigated. LDLr knockout female mice were mated with LDLr heterozygous males and vice versa to obtain embryos of the same litter that are either heterozygous or lack LDLr altogether. All mice were maintained on a regular chow diet throughout the lifespan. At 13.5 days of gestation, dams were intraperitoneally supplemented with a physiological dose of 20–50 μg/g body weight of bC. Maternal serum, liver, placenta and embryos were collected after 24 hours and analyzed by HPLC and qPCR.Hepatic bC levels were reduced in LDLr knockout dams. Placenta of heterozygous embryos had higher bC levels as compared to the knockout placenta, an effect observed only in case of LDLr knockout dams. Maternal and embryonic genotype did not have an effect on bC levels in embryos. Preliminary qPCR analysis of placenta revealed that both bC supplementation and LDLr genotype of the placenta had an effect on the mRNA expression of genes involved in lipid metabolism. These results suggest that LDLr mediates uptake of bC 1) in the liver and 2) in the placenta of dams lacking LDLr. In addition to this, the data suggested that a single dose of bC at mid‐gestation may alter genes involved in the lipid metabolism in the placenta and the embryo.Grant Funding Source: NIH
Effect of dietary mannoheptulose on whole body glucose and energy metabolism in adult neutered male Labrador Retrievers
Authors: McKnight Leslie L , Flickinger Elizabeth A , Davenport Gary , France James , Shoveller Anna K 
Published: June 2021

The objective of this study was to determine the effect of dietary mannoheptulose (MH) on glucose and energy metabolism in adult male neutered Labrador Retrievers (N = 6, 5.4 y). This study was designed as a cross‐over with each dog receiving both dietary treatments, control (CON) and MH (200 mg/kg), in random order. Fasting and post‐prandial respiratory quotient (RQ) and energy expenditure (EE) were determined by indirect calorimetry (d 16). Glucose kinetics were assessed during fasting and repeated meal feeding using indirect calorimetry and a primed continuous infusion of U‐13C‐glucose (d 18). A fasting biceps femoris muscle sample was obtained (d 21/22) to determine protein content of phosphorylated and total adenosine monophosphate‐activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC). Diet did not affect plasma glucose, insulin, FFA or glucose turnover during fasting or repeated meal feeding. There were no diet‐related differences in glucose oxidation or energy metabolism in the fed state. However, there were trends for MH to increase RQ (p=0.14) and glucose oxidation (p=0.16) and to lower the ratio of phosphorylated to total AMPK protein content (P=0.08) during fasting. These findings suggest daily MH feeding may affect carbohydrate utilization during fasting.Grant Funding Source: Procter and Gamble Pet Care
Effects of Elderberry Juice on Citrobacter rodentium‐induced Host Responses in C57BL/6J Mice
Authors: Lu Chi‐Hua , Browning Jimmy D , Spagnoli Sean T , Lei Wei , Eichen Peggy A , Fritsche Kevin L 
Published: June 2021

IntroductionC. rodentium (CR) is a murine pathogen that shares characteristics with human pathogenic E. coli. Elderberry juice (EJ) has been shown to possess anti‐inflammatory activities. The goal of this study was to evaluate EJ's impact on host immune responses to CR infection.Experimental DesignAnimals (n=40) were randomly assigned into four treatment groups: 1) Uninfected: CR (−), AIN93G diet with no EJ (0% EJ diet); 2) CR (+), 0% EJ diet; 3) CR (+), 0.4% EJ diet; 4) CR (+), 2% EJ diet. CR was given by a single oral dose (10^9 CFU) on day 0, and animals were sacrificed on day 10.ResultsBodyweight and fecal CR load were similar among groups post‐challenge. H&E staining showed that CR increased colon mucosal height (50%), and pathology scores of inflammation (2‐fold), epithelial defects (2.5‐fold) and hyperplasia (2‐fold). Quantitative PCR showed that CR increased TNF‐alpha (3‐fold), IFN‐gamma (2‐fold) and IL‐17 (to detectable) expression in colon. However, when comparing all infected groups, no such differences were observed by EJ treatment, except for higher IL‐10 expression in colon (2‐fold, p<0.05). Systemic anti‐oxidative status was also evaluated by ORAC and TBARS in plasma and liver, and no significant differences were found among all groups.ConclusionExcept for elevating colonic IL‐10 mRNA expression, EJ treatment did not significantly alter other inflammatory responses to GI infection by CR.Grant Funding Source: NIH P50AT006273
Iron stores and home stimulation independently relate to infant development in a rural Indian community with high rates of infant anemia
Authors: Rao Sylvia Fernandez , Black Maureen , Hurley Kristen , Balakrishna Nagalla , Radhakrishna KV , Tilton Nicholas , Reinhart Greg , Harding Kim , Nair K. Madhaven 
Published: June 2021

ObjectiveExamine how iron stores and home stimulation relate to infant development in rural India.MethodsEnrolled 497 infants age 6–12 mo. Calculated weight‐age, length‐age, & weight‐length z‐scores (WAZ, HAZ, WHZ). Assessed home stimulation (HOME Inventory), motor, language & visual reception (Mullen Scales of Early Learning) & socioemotional (Brief Infant‐Toddler Socio‐Emotional Assessment). Associations of iron stores & home stimulation with development estimated by analyses of variance, adjusted by child age, WAZ, HAZ, WHZ, hemoglobin (Hb), B12, C reactive protein, maternal education & household assets.Results71% had adequate iron stores (ferritin>;12 μg/L), 66% were anemic (Hb<11 g/dL), 20% stunted (HAZ<‐2) & 19% underweight (WAZ<‐2). Ferritin was positively associated with fine motor (p=.039), receptive language (p=.045), & socioemotional (p=.023), but not gross motor, expressive language, or visual reception. Home stimulation was positively associated with receptive (p=.025) & expressive language (p=.002), visual reception (p<.001), & socio‐emotional (p<.001), but not gross/fine motor.ConclusionIron stores & home stimulation are independently associated with infant development, supporting evaluation of an integrated micronutrient‐infant development trial.Support: Mathile Institute & Micronutrient Initiative
Influence of dietary saturated fat content on adiposity, macrophage behavior, inflammation, and metabolism: composition matters
Authors: Enos Reilly , Davis J. Mark , Velazquez Kandy , McClellan Jamie , Carnevale Kevin , Murphy E. Angela 
Published: June 2021

We examined the effects of three high‐fat diets differing in the percentage of total calories from saturated fat (SF) (6%, 12%, and 24%), but identical in total fat (40%), on body composition, macrophage behavior, inflammation, and metabolic dysfunction in mice. Diets were administered for 16 weeks. Body composition and metabolism (glucose, insulin, triglycerides, LDL‐C, HDL‐C, total cholesterol) were examined monthly. Adipose tissue (AT) expression of marker genes for M1 and M2 macrophages and inflammatory mediators (TLR‐2, TLR‐4, MCP‐1, TNF‐α, IL‐6, IL‐10, SOCS1, IFN‐γ) was measured along with activation of NFκB, JNK and p38‐MAPK. AT macrophage infiltration was examined using immunohistochemistry. Circulating MCP‐1, IL‐6, adiponectin, and leptin were also measured. SF content, independent of total fat, can profoundly affect adiposity, macrophage behavior, inflammation, and metabolic dysfunction. In general, the 12%‐SF diet, most closely mimicking the standard American diet, led to the greatest adiposity, macrophage infiltration, and insulin resistance (IR), whereas the 6%‐SF and 24%‐SF diets produced lower levels of these variables with the 24%‐SF diet resulting in the least degree of IR and the highest TC/HDL‐C ratio. Macrophage behavior, inflammation and IR following HFDs are heavily influenced by dietary SF content, however, these responses are not necessarily proportional to the SF%. This work was supported by an ASPIRE (Advanced Support Programs for Innovative Research Excellence) grant from the University of South Carolina to E.A.M.Grant Funding Source: ASPIRE
Aging alters global hepatic DNA hydroxymethylation in mice, as determined by a novel LC/MS‐MS method
Authors: Tammen Stephanie A. , Dolnikowski Gregory G. , Ausman Lynne M. , Friso Simonetta , Choi Sang‐Woon 
Published: June 2021

Aging is associated with changes in global DNA methylation (mC), but changes in DNA hydroxymethylation (hmC) are not established due to a relative lack of methods available to measure hmC. Both modifications can affect gene expression and may be important in aging. We have developed a method to measure 5′‐methyl‐2′‐deoxycytidine and 5′‐hydroxymethyl‐2′‐deoxycytidine in DNA using liquid chromatography/tandem mass spectrometry (LC/MS‐MS) and used this method to assess global hmC and mC levels in hepatic tissue from young (9 months; n=10) and old (23 months; n=6) C57BL/6 male mice. DNA was enzymatically hydrolyzed and isotopomers [15N3]‐2′‐deoxycytidine and (methyl‐d3, ring‐6‐d1)‐5‐methyl‐2′‐deoxycytidine were added as internal standards. The mixture of DNA hydrolysates and internal standards were separated through LC, and nucleosides of interest were detected by MS‐MS in positive ion mode using multiple reaction monitoring. Global mC and hmC levels were calculated as a percentage of total deoxycytidine residues in genomic DNA. Liver tissue from old mice had significantly higher global hmC relative to young mice (0.32±0.02% vs 0.24±0.01%; p=0.02), while mC levels did not change. Using this new method we have found that aging is associated with an increase in global DNA hmC, a finding that may be useful in understanding the physiological mechanisms behind aging.Grant Funding Source: NIH grant R01 AG025834
Low‐glycemic index diets prevent type 2 diabetes in the Nile rat
Authors: Bolsinger Julia , Pronczuk Andrzej , Hayes KC 
Published: June 2021

The Nile rat (NR) is a novel model for type 2 diabetes (T2DM) and metabolic syndrome sensitive to metabolic stress from simple carbohydrates (CHO). Three experiments assessed the effects of a low‐glycemic index CHO (green lentils, GL) on T2DM. Expt 1 compared a GL diet directly with a semipurified hiCHO diet having identical %En from CHO:fat:protein (70:10:20). Expt 2 assessed reversibility of hyperglycemia by comparing a modCHO‐GL diet (45:25:30) to diabetogenic semipurified hiCHO (70:10:20) or lab chow (#5020) diets in 3 separate studies. Expt 3 examined young Nile rats “primed” from weaning for 7wks with the modCHO‐GL diet (45:25:30) before being challenged with stressful semipurified hiCHO (70:10:20) or modCHO (40:40:20) diets based on glucose and starch. 1. Compared to the hiCHO semipurified diet with the same macronutrient composition, the GL diet induced significantly less diabetes. 2. GL substantially reversed hyperglycemia, especially in young (<4mo) diabetic rats. 3.”Priming” rats with GL prior to hiCHO resulted in less severe diabetes compared to previous studies without priming. Positive influences on other metabolic parameters such as liver and kidney weight and plasma lipids also were observed. Since the NR mimics T2DM in humans, GL or components therein may represent a potentially useful adjunct for T2DM control in humans.Funding source: Foster Biomed Res Lab and the Malaysian Palm Oil Board
Botanicals inhibit castrate‐resistant prostate cancer via mechanisms involving AMPK, inhibition of lipogenesis, mTOR‐mediated proliferation, and histone modification
Authors: Zhao Yi , Whelan Jay 
Published: June 2021

Reprogramming of metabolic pathways and abnormal acetylation of DNA are two common features of cancer cells, including prostate cancer (PCa). Our results show that polyherbal mixtures of botanicals, like Zyflamend®, can modify lipogenesis in CWR22Rv1 cells (a castrate‐resistant human PCa cell line) by enhancing the activity of 5'adenosine monophosphate (AMP)‐ activated protein kinase (AMPK), a potential tumor suppressor protein that functions as a central energy sensor within the cell. By increasing the phosphorylation of AMPK, Zyflamend® decreases de novo lipid biosynthesis by decreasing the activity of acetyl‐CoA carboxylase (ACC) and the expression of FASN and SREBP1c. Also via AMPK, Zyflamend® inhibits the activity of mTORC1 complex by directly phosphorylating Raptor, decreasing the activity of P70 (S6K, the marker for protein synthesis). All of these effects can be mimicked by treatment of AICAR (activator of AMPK). Furthermore, Zyflamend® increases the acetylation of DNA via mechanisms that appear to involve ATP‐citrate lyase (ACLY). Thus, our results suggest that botanicals, via AMPK, inhibit castrate‐resistant prostate cancer via mechanisms that involve lipid metabolism that may reshuttle acetyl CoAs for histone acetylation, and inhibition of mTOR mediated cell proliferation.Grant Funding Source: This research was supported in part by Tennessee Agricultural Experiment Station
Principal human milk oligosaccharides utilized by human gut microbiota
Authors: Yu Zhuo‐Teng , Liu Bo , S David 
Published: June 2021

Human milk oligosaccharides are poorly digested and absorbed in the small intestine, allowing their passage into the colon, where they influence colonization by the microbiota. The ability of individual major fucosylated and sialylated human milk oligosaccharides to promote growth and physiologic activity of 25 human intestinal microbes was investigated. 2′‐Fucosyllactose, 3‐ Fucosyllactose, and Lactodifucotetraose stimulated most Bifidobacteria spp. and Bacteroides spp. to grow and produce abundant lactate or short chain fatty acids. 3′‐sialyllactose and 6′‐ sialyllactose promoted moderate growth of B. longum JCM7007, 7009, 7010, 7011, 1272, 11347, ATCC15708, B. thetaiotaomicron ATCC29148, and C. leptum ATCC29065; these bacteria produced lactate or short chain fatty acids or both. In contrast, L. rhamnosus ATCC53103, E. facalis ATCC29200, S. epidermidis ATCC12228 and E. coli K12 did not consume the milk oligosaccharides. In summary, specific Bifidobacteria and Bacteroides differentially digest specific individual human milk oligosaccharides, especially the major fucosylated milk oligosaccharides, and these may prove useful for treating dysbiosis of the microbiota and associated inflammatory disorders.Grant Funding Source: HD013021, AI075563, and Abbott Nutrition
Just what the doctor ordered: novel medical student nutritional education through community‐based cooking classes
Authors: Birkhead Andrew Gartner , Loyd Jacob , Leong Benjamin , Joo Esther , Monlezun Dominique , Kay Danielle , Abu‐Shamat Layla , Sarris Leah , Harlan Timothy 
Published: June 2021

Adams et al. (2010) demonstrated in a survey of 126 US medical schools that most medical nutrition curriculum hours are taught in a passive lecture format rather than within an active clinical context. This may explain Spencer et. al. (2010) who reported that only 19% of graduating US medical students felt prepared to use nutrition counseling in practice. Until this year Tulane University's medical nutrition curriculum was limited to this model. Tulane's newly created Center for Culinary Medicine combined with the medical student service learning program in an effort to improve nutrition education. Students are required to log 50 hours of community service, which they can now spend learning and teaching principles of cooking and nutrition to patients in ambulatory settings in addition to the traditional curriculum. To date approximately 25% of the Tulane medical student body has participated in nutrition service learning. Students who opted to participate will be compared to students who only had the lecture component by examining perceived competence to counsel patients on a wide range of nutrition topics. Research support: Tulane University Center for Culinary Medicine.Grant Funding Source: Tulane University Center for Culinary Medicine
Characterization of temporomandibular joint disc in human by histological and biochemical analyses
Authors: Lerma Tanya , Taylor Victor W. , Guttmann Geoffrey D. 
Published: June 2021

The temporomandibular joint (TMJ) is characterized by mandibular condyles, capsule, lateral pterygoid, articular surface of the temporal bone, ligaments, and articular disc. For this study the focus is complex articular disc attachments. The main component of the disc is fibrocartilage while its extracellular matrix (ECM) is predominantly composed of collagen type II, sulfated glycosaminoglycan (GAG) and proteoglycans. The purpose is to use histological techniques to investigate components of TMJ disc attachments and quantify constituents of the disc using biochemical assays. Microscopic investigation of attachments provides information to understanding the mechanics of the TMJ disc and an understanding of the relationship between disc and attachments. Six (6) fresh un‐embalmed TMJ disc‐attachment complexes were dissected from willed body donors. TMJ discs were further dissected into five regions and disc attachments were dissected into six regions to emulate a previous study by Willard et al (2011), which used porcine TMJ. Histology and biochemical assays were performed on each region to quantify ECM components. Histological analysis provided information on distribution of components in the complex.Grant Funding Source: None