bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of phospholipid synthesis in lipid‐mediated signaling and regulation in yeast
Authors: Henry Susan Armstrong , Jesch Stephen A. , Nunez Lilia R. , Villa‐Garcia Manuel , Gaspar Maria L. , Aregullin Manuel A. , Lee So Jin , Chang Yu‐Fang 
Published: June 2021

Rapid genome‐wide changes in the transcription of hundreds of genes in yeast cells occur in response to changes in lipid metabolism that accompany the provision of inositol, the immediate precursor to phosphatidylinositol (1, 2). Changes in the synthesis and turnover of lipids that accompany these transcriptional responses include decreases in phosphatidic acid and CDP‐diacylglycerol and an increase in the rate of phosphatidylinositol synthesis and phosphatidylcholine turnover (3, 4). These changes in the patterns of synthesis or turnover of these lipids influence several major signaling pathways and transcriptional networks. Moreover, the Protein Kinase C pathway is involved in maintaining lipid homeostasis in cells deprived of inositol when choline is present. A screen of viable gene deletion mutants for phenotypes associated with misregulation of lipid metabolism identified many mutants defective in several major stress response pathways. We will discuss the roles of these signaling pathways in cellular homeostasis under conditions of changing lipid metabolism.This work is supported by NIH grant GM‐19629.
Increased consumption of legumes improves arterial stiffness in peripheral vascular disease independent of blood pressure, weight and serum cholesterol
Authors: Zahradka Peter , Guzman Randy , Weighell Wendy , Wright Brenda , Baldwin Alanna , Louis Sherif , Rodriguez‐Leyva Delfin , Taylor Carla G. 
Published: June 2021

BackgroundEating fibre‐rich, low glycemic legumes may benefit cardiovascular health by reducing plasma lipid levels. We therefore undertook a clinical study to address the hypothesis that increased legume consumption would improve arterial stiffness.MethodsIndividuals with peripheral arterial disease were given ½ cup mixed legumes daily for 8 wks.ResultsNo changes in glycated hemoglobin, blood pressure, body weight, triglycerides or HDL cholesterol were detected relative to baseline values, but there were significant decreases in total and LDL cholesterol. There was an improvement in ankle‐brachial index (ABI) and a corresponding decrease in arterial stiffness (by pulse wave analysis), but serum markers of endothelial dysfunction or inflammation remained constant. Interestingly, the improvements in ABI and cholesterol were not correlated.ConclusionsThese data indicate that a legume‐rich diet can elicit major improvements in arterial function in the absence of changes in either body mass or blood pressure. Furthermore, the lack of correlation with serum cholesterol levels suggests improved vascular function was not a consequence of the high fibre and low glycemic index properties of the legumes. Finally, the absence of changes in circulating markers of endothelial dysfunction suggests the positive effects on arterial stiffness are mediated by another mechanism.Funding from Pulse Canada.
The Healthy Eating Index scores of low‐income women in early postpartum and its association with lipid profiles
Authors: Shah Bijal Sanghani , Cahill Jodi , Lu Hongxing , Freeland‐Graves Jeanne H 
Published: June 2021

The Healthy Eating Index (HEI) is a composite tool that assesses the degree to which individuals conform to the recommendations of the 2005 Dietary Guidelines. Previous versions of this index have shown to influence lipid levels. The objective was to evaluate the diet quality of triethnic, overweight/obese women in early postpartum (n=131) using the HEI‐2005 and its ability to reflect serum lipids, a cardiovascular risk factor. Dietary data were collected via a 24‐hour recall and 3 day food intake records. Anthropometrics and serum lipids also were measured. Less than 40% had adequate intakes of fruits, total vegetables, whole grains, low‐fat milk and meat and oil. Additionally, more than 60% exceeded the guidelines for sodium, saturated fats and discreationary calories. Those in the highest tertile of HEI scores had lower BMI (35.4 vs. 32.5), body fat % (41.6 vs. 42.5), LDL (135.1 vs. 118.4) and triglycerides (148.8 vs.129.2) and greater HDL (51.9 vs.56.2) (P for trend<0.01) than those in lowest. Early postpartum women had minimal compliance to dietary guidelines. Moreover, HEI scores were reflective of anthropometrics and lipid profiles. Interventions that focus on improving lipid profile might benefit from inclusion of dietary modification component that improves HEI scores.Grant Funding SourceTX Coordinating Board # UTA00‐377
Dual‐localization of ZnT2 to mitochondria and exocytotic vesicles redistributes zinc pools in mammary cells
Authors: Seo Young Ah , Kelleher Shannon L 
Published: June 2021

ZnT2 plays a major role in mammary gland zinc (Zn) secretion; however, the mechanisms through which ZnT2 exports Zn from the mammary gland are not understood. ZnT2‐attenuation significantly reduced 65Zn export in cultured mammary epithelial cells (HC11) illustrating its role in Zn export in mammary gland. Expression of a ZnT2‐HA fusion protein increased vesicular Zn pools (quantified by FluorZin‐3 fluorescence) by ~35%, likely through increased Zn accumulation in the endoplasmic reticulum and exocytotic vesicles (co‐localized with calnexin and VAMP8 by confocal microscopy, respectively). Interestingly, endogenous ZnT2 was detected in mitochondria (co‐localized with COX IV by confocal microscopy) which was verified by immunoblotting proteins from isolated mitochondria that were rigorously digested with proteinase K. ZnT2‐attenuation significantly reduced mitochondrial ZnT2 abundance and Zn uptake. Importantly, expression of a ZnT2‐HA fusion protein was detected in mitochondria which expanded mitochondrial Zn pools (~23%) as quantified by RhodZin‐3 fluorescence (mitochondria‐specific Zn fluorophore). Taken together, our data indicate that ZnT2 is a dual‐localized protein which resides in mitochondria and intracellular vesicles. We propose that alterations in the sub‐cellular localization of ZnT2 modulates intracellular Zn pools in response to changes in cellular Zn requirements.Grant Funding SourceNIH
High maternal folate intake by Sprague Dawley rats results in higher weight gain and lower plasma folate in male offspring
Authors: Huot Pedro S. P. , Ly Anna , Reza‐López Sandra , Cho Daniel , Duan Jiuhua , Kim Young‐In , Szeto Ignatius M.Y. , Anderson G. Harvey 
Published: June 2021

High multivitamin intake during pregnancy leads to increased weight gain, food intake, and hyperinsulinemia in rat offspring (Szeto et al. Am J Physiol 2008; 295: R575‐82). The objective of this study was to investigate the role of maternal folate intake on offspring body weight (BW) and hypothalamic gene expression. Pregnant Sprague Dawley rats (n=10/group) were randomized to the AIN‐93G diet containing either the recommended (RF) or 2.5‐fold the folate content (HF) during pregnancy and lactation. All offspring were weaned to the RF diet. BW was measured from 1 wk post‐weaning (pw) to 25 wk pw. Plasma and liver folate levels were measured and hypothalamic gene expression of leptin receptor (LR) and POMC were determined by real‐time RT‐PCR. Males from HF dams were 6% heavier compared with those from RF dams (p<0.0001). Males from HF dams had 27% lower plasma folate compared to males from RF dams (p=0.01), while there were no differences in liver folate levels. Males from HF dams had 39% lower POMC mRNA compared to males from RF dams (p<0.05). No differences in LR mRNA levels were detected. In conclusion, a moderate increase in maternal folate intake resulted in higher BW, which may be related to lower hypothalamic POMC expression, and lower plasma folate concentrations in the male offspring.Grant Funding SourceCIHR‐INMD (OOP‐77980), Ontario Graduate Scholarship
The effect of a high multivitamin diet during the first gestation on the dams and their offspring from the first and second pregnancy
Authors: Reza‐Lopez Sandra , Szeto Ignatius M. , Huot Pedro S.P. , Ma David W.L. , Anderson G. Harvey 
Published: June 2021

High multivitamin intake during pregnancy of the Wistar rat results in increased body weight, food intake and characteristics of the metabolic syndrome in the offspring (Szeto IM et al. Am J Physiol Regul Integr Comp Physiol 2008; 295: R575‐82). The objective of the study was to investigate the effect of a high multivitamin diet during pregnancy on body weight (BW) and glucose tolerance of the dams and their offspring after both the first and second pregnancy. Wistar rats (n=19) received the AIN‐93G diet with either the required (RV) or 10‐fold amount of multivitamins (HV) during the first pregnancy. After delivery all dams received only the RV diet and were mated again at 12 wk post‐weaning (PW). The offspring from both pregnancies were weaned to the RV diet and followed for 15 wk PW. BW and oral glucose tolerance were measured in the dams and offspring. Dams given the HV diet during the first pregnancy gained more weight at 12 and 20 wk after the first and second litters, respectively. First litter females, but not males, from the HV dams gained less BW than those from RV dams (239±7 vs 271±12g, p=0.03). Second litter males, but not females, from dams given the HV diet during the first pregnancy gained more BW (592±14 vs 539±18g, p=0.04) and had 7% higher glucose response at 4 wk PW. In conclusion, the effects of a high vitamin diet during the first pregnancy persist after the second pregnancy.Grant Funding SourceCIHR‐INMD‐OOP‐77980 and CONACyT to S. Reza
Diet and intestinal sulfate reducing bacteria populations distinguish native Africans from Caucasian and African Americans
Authors: Nava Gerardo M. , Ou Junhai , O'Keefe Stephen J. , Gaskins H. Rex 
Published: June 2021

Americans of African (AAs) descent have the highest incidence and mortality from sporadic colorectal cancer (CRC) in the USA (65:100,000 vs. 50:100,000 in Caucasian Americans (CAs). In contrast, native Africans (NAs) are rarely diagnosed with the disease (<1:100,000). Reduced susceptibility to CRC in NAs is associated with low consumption of animal protein and greater microbial production of colonic methane compared to AAs and CAs. The present study examined in stool samples from these three groups the extent to which populations of sulfate reducing bacteria (SRB) vary. These bacteria contribute to an alternate pathway for colonic hydrogen disposal and in the process generate the potent genotoxin hydrogen sulfide. Molecular ecological analysis using a nested PCR‐based approach and principal component analysis revealed that Desulfovibrio spp. (major genus of colonic SRB) 16S rRNA gene profiles cluster in NAs (n = 19) compared to those of AAs (n = 18) and CAs (n = 17). This observation is consistent with the hypothesis that interactions among genetic background, diet and microbial mechanisms of hydrogen disposal may influence susceptibility to sporadic colorectal cancer.Grant Funding SourceNational Institutes of Health
Chemoprotective fish oil/pectin diets temporally alter gene expression profiles in exfoliated colonocytes
Authors: Cho Youngmi , Turner Nancy D. , Taddeo Stella S. , Davidson Laurie A. , Wang Naisyin , Vannucci Marina , Carroll Raymond J. , Chapkin Robert S. , Lupton Joanne R. 
Published: June 2021

We have demonstrated that fish oil/pectin (FP) diets are protective against colon cancer compared to corn oil/cellulose (CC) in part by upregulating apoptosis at the promotion stage of carcinogenesis and suppressing peroxisome proliferator‐activated receptor δ(PPARδ) expression at the tumor stage. To elucidate the underlying mechanisms whereby FP diets induce apoptosis and suppress PPAR signals, we analyzed the temporal gene expression profiles from exfoliated rat colonocytes. Rats consumed diets containing either FP or CC and were injected with azoxymethane (2x, 15 mg/kg BW, sc). Fecal material was collected at 7, 14, and 28 wk in the same rats and was used for poly A+ RNA extraction. Gene expression signatures were determined using GE Codelink arrays. GO analysis identified 10 genes upregulated by FP at the promotion stage of carcinogenesis involved in apoptosis (p=0.006). KEGG pathway analysis indicated that FP suppressed seven genes in the PPAR signaling pathway at the tumor stage (p=0.056). We conclude that the effects of chemotherapeutic diets on epithelial cell gene expression can be monitored noninvasively throughout the tumorigenic process.Grant Funding SourceFunded by NSBRI NASA NCC 9‐58 and NIH (CA59034, CA57030).
Associations of specialty herbal supplements with lung and colorectal cancer risk
Authors: Satia Jessie A , Littman Alyson , Slatore Christopher , Galanko Joseph , White Emily 
Published: June 2021

AimMillions of Americans use dietary supplements with little knowledge about their benefits or risks. We examined associations of various specialty herbal supplements with lung and colorectal cancer (CRC) risk.MethodsEligible men and women, 50‐76 y, in the VITAL (VITamins And Lifestyle) cohort Study (n=77,126) completed a 24‐page baseline questionnaire. Duration (years) and frequency (days/week) of use over the previous 10 years was collected on 20 specialty herbal supplements. Dose was not assessed due to lack of accurate potency information. Supplement exposure was categorized as "no use" or "any use" over the previous 10 years. Hazard ratios (HR) were estimated from Cox regression models, with control for covariates. Incident lung (n=665) and CRC cancers (n=428) were obtained from the SEER cancer registry.ResultsAny use of glucosamine and chondroitin over the previous 10 years was associated with significantly lower lung cancer risk: HR: 0.74 (95% CI: 0.58, 0.94) and HR: 0.72 (95% CI: 0.54, 0.96), respectively. There were statistically significantly inverse associations of fish oil, glucosamine, chondroitin, MSM, and St. John's Wort (HR: 0.35, 95% CI: 0.14, 0.85) with CRC risk; garlic pills were associated with a significant 35% elevated risk.ConclusionsGlucosamine and chondroitin were associated with reduced risk for both cancers, whereas use of garlic pills correlated with higher CRC risk. Given the popularity of herbal supplements, studies examining their effects on risk for cancer and other diseases are urgently needed.
Carbohydrate‐related dietary factors and plasma adiponectin levels in healthy adults in the Framingham Offspring Cohort.
Authors: McKeown Nicola Mary , Liu Enju , Meigs James B , Rogers Gail , D'Agostino Ralph , Jacques Paul 
Published: June 2021

Diet may influence circulating adiponectin levels by improving insulin sensitivity. We examined the associations between carbohydrate‐related dietary factors and plasma adiponectin levels in healthy adults aged 26‐81 y (n= 979 men and 1227 women). Dietary intakes were assessed using a FFQ. Fasting plasma adiponectin was assayed with an immunoassay kit. After adjustment for age, sex, BMI, total energy intake, current smoking status, % energy from fat and alcohol consumption, higher intakes of dietary fiber were positively associated with plasma adiponectin (10 % difference between highest (Q5) and lowest (Q1) quintile; p trend= 0.04), while dietary glycemic index (DGI) inversely associated with plasma adiponectin (10% difference between Q5 and Q1; p trend <0.001). A marginally significant positive association was observed between cereal fiber and whole‐grain intakes and plasma adiponectin levels (p trend =0.06). However, only the association between DGI and plasma adiponectin levels remained significant after adjustment for fasting insulin. Total carbohydrate, fruit, vegetable, legume/nut fibers, glycemic load, and refined grain intakes were not associated with adiponectin levels. In conclusion, a high DGI may influence adiponectin by mechanisms independent of insulin.Supported in part by funding from General Mills Bell Institute of Research, the USDA Agreement 58‐1950‐7‐707 and the Framingham Heart Study of the National Heart Lung and Blood Institute of the NIH (Contract N01‐HC‐25195)
Glucose lowering effect of lupin seed γ‐ conglutin in hyperglycaemic rats upon chronic treatment
Authors: Lovati Maria Rosa , Manzoni Cristina , Pizzagalli Anna , Duranti Marcello Maria , Castiglioni Silvia 
Published: June 2021

Aim of the study was to evaluate the effect of a chronic oral administration of conglutin γ, a lupin seed protein, in male Sprague Dawley rats in which the hyperglicemia was induced by drinking water containing 10% d‐glucose. A dosage of 100 mg/kg b.w. of conglutin γ was administered daily to rats for 21 days. Conglutin γ administration induced a statistically significant reduction in plasma glucose (‐25%) and triglyceride (‐20%) levels as well as a reduction of glycemia after the oral glucose loading, comparable to that of metformin. In order to assess the mechanism underlining this biological effect, Hep G2 cells, grown in DMEM containing different glucose concentrations (5.5 mM, 11 mM and 17 mM) for 24, 48 and 72 h, were exposed, respectively to 0.5 mg/mL conglutin γ 10 mM metformin or 100nM insulin. Conglutin γ induced in Hep G2 cells, in all experimental conditions, an increased glucose consumption (from 1.5 to 2.5 fold ) which was more evident after 24h of incubation. Moreover, the addition of conglutin γ potentiated, in this in vitro model, the activity of insulin and metformin in cell glucose uptake. These findings represent the first molecular evidence of the possible use of a legume protein in the control of glycemia.Supported in part by a grant of MIUR from Italy
In vivo proton NMR spectroscopy reveals an altered neurochemical profile in copper deficient rat brain
Authors: Prohaska Joseph , Gybina Anna 
Published: June 2021

Copper deficiency in mammals is associated with impaired brain development and mitochondrial dysfunction. Although the precise mechanisms are unknown disturbances in energy metabolism due to lower cytochrome c oxidase is a common hypothesis. Perinatal copper deficiency was produced in Holtzman rat dams and evaluated in male offspring. Biochemical analyses of rat brains indicated that compared to copper adequate (CuA) rats copper‐deficient (CuD) rats had lower copper and iron levels. In vivo proton NMR spectroscopy was used to quantify 18 cerebellar and hippocampal metabolites on postnatal day 21 (P21). Lower concentration of ascorbate was measured in both brain regions in CuD rats, which was in good agreement with previously published in vitro HPLC data. Both regions also demonstrated lower N‐acetylaspartate levels suggestive of impaired mitochondrial function and/or delayed brain development. For other metabolites, the P21 neurochemical profile of CuD rats was remarkably similar to CuA rats but uniquely different from iron‐deficient or chronic hypoxia models. Further research is needed to determine the neurochemical consequences of copper deficiency.Supported in part by NIH HD‐39708 to JP and Center for Magnetic Resonance Research is in part supported by NIH grants P41 RR008079, P30 NS057091 and W.M. Keck Foundation.
Teaching and learning anatomy interactively online in the new digital age of 21st century
Authors: Ding Yang , Wilson Timothy Dale 
Published: June 2021

To address decreasing in‐class hours and lack of cadaveric dissection time dedicated to anatomical education, the authors propose a new interactive methodology for teaching anatomy online. This new curriculum will implement virtual reality technology through the open source software called realXtend to provide an engaging learning experience for students as well as allowing greater educational access for learners and educators alike. The can take place inside or outside the traditional learning environment. Once fully operational, realXtend allows users to freely interact with the digital models within a virtual three‐ dimensional world and examine the fine detail of anatomical structures which may not be clearly visible in cadaveric dissections. In addition, realXtend grants users the freedom to freely scale, move and rotate any of the anatomical structures to facilitate spatial perception. This curriculum is ideally implemented concurrently with cadaveric dissections to mutually complement each other, thus maximizing overall effectiveness in a rich learning environment for students. We plan to incorporate this technology in the upcoming year in Health Science undergraduate anatomy curriculum to complement the lack of actual dissections in the anatomy courses.Grant Funding SourceInternal
Prion Proteins: One Surprise After Another
Authors: Lindquist Susan Lee , Alberti Simon , Halfmann Randal , Jackson Walker 
Published: June 2021

Proteins must fold into the right shape to do their jobs. When misfolded proteins persist, the consequences can be deadly, leading to devastating diseases. In the case of prion proteins, altered forms can template their change in shape to other proteins of the same type, leading to transmissible spongiform encephalopathies. We engineered mice to express the mammalian prion protein PrP with a mutation linked to human FFI (fatal familial insomnia). These mice develop pathology that is very similar to that of FFI, and the disease phenotype was readily transmitted to mice expressing wild‐type PrP, demonstrating that a point mutation in PrP is sufficient not only to cause a distinct neurodegenerative disease but also the spontaneous appearance of prion infectivity.In yeast cells, prions are not toxic, but can provide helpful new phenotypes. The prion state involves conversion of a protein domain into an amyloid fold, and this occurs through a molten oligomeric intermediate. We identified the critical nucleating contacts involved in the conversion of Sup35, a yeast prion involved in translation termination. Using peptide arrays, we determined that this region also controls two previously mysterious properties of prion biology: the species barrier and the formation of distinct prion strains.
Estimating distributions of usual total nutrient intake: A comparison of available methods
Authors: Dodd Kevin W , Bailey Regan , Wilger Jaime , Sempos Chris , Dwyer Johanna , Radimer Kathy , McDowell Margaret , Johnson Cliff , Picciano Mary Frances 
Published: June 2021

Distributions of usual nutrient intake are used to monitor a population's nutritional status. It is vital to consider nutrient intakes from all sources, including dietary supplements (DS). This study compared strategies for estimating distributions of total nutrient intake based on data from the National Health and Nutrition Examination Survey (NHANES). In the 2003‐2004 NHANES, two 24‐hour dietary recalls (24HR) were collected; detailed information about type, consumption frequency, and amount of nutrients from DS was collected through an interviewer‐administered questionnaire. A simulation study compared several approaches for combining the 24HR and DS data for calcium intake. Four methods (ISU, NAS, BCP, and NCI) for adjusting 24HR nutrient data were extended to use DS data in three ways by adding:
average intake from DS to adjusted 24HR intakes,
average intake from DS to each 24HR intake before adjustment, or
single‐day DS dosages to none, some, or all of the 24HRs before adjustment.We find that adding average DS intake to adjusted 24HR intakes leads to unbiased estimates for percentiles, but adding DS intake to 24HR intakes before adjusting can lead to substantial bias. These results suggest that complex relationships existing between DS use and habitual diet must not be ignored.