bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein and amino acid biofortification of staple crops has potential to reduce population risk of protein inadequacy in Sub‐Saharan Africa
Authors: Suri Devika , Strutt Nicholas , Ghosh Shibani 
Published: June 2021

IntroductionPopulations dependent on starchy staple crops are at risk of protein inadequacy. Biofortification can improve nutritional quality of food crops. This study examined potential of protein and amino acid biofortified staple crops to reduce risk of protein inadequacy in six Sub‐Saharan African and South Asian countries.MethodsFAO food balance sheets and USDA nutrient data were used to determine mean per capita nutrient supply and estimate population risk of protein inadequacy (PRPI), adjusting for protein quality using the PDCAAS method. We modeled increases in protein/amino acids of six crops to improve total protein/protein quality. PRPI was calculated using 2005 food supply, with 60% substitution of domestically produced crop with biofortified crop.ResultsBiofortified crops reduced PRPI from: 77% to 54% in Mozambique (maize); 21% to 14% in Nigeria (sorghum); 18% to 12% in Uganda (plantain); 44% to 23% in Zambia (cassava). PRPI in Bangladesh (41%) and India (31%) did not improve with biofortified rice and wheat indicating deficit of total protein rather than poor protein quality at the food supply level.ConclusionProtein/amino acid biofortification of starchy staple crops has the potential to reduce PRPI in populations with low protein quality in their overall food supply. Further work will investigate effect of biofortified crops on protein inadequacy at an individual level.
Identification of N‐acetyltaurine as a novel metabolite of ethanol through metabolomics‐guided biochemical analysis
Authors: Shi Xiaolei , Yao Dan , Chen Chi 
Published: June 2021

The influence of ethanol on small‐molecule metabolome and the role of CYP2E1 in ethanol‐induced hepatotoxicity were investigated using liquid chromatography‐mass spectrometry (LC‐MS) based metabolomics platform and Cyp2e1‐null mouse model. Histological and biochemical examinations of ethanol‐exposed mice indicated that the Cyp2e1‐null mice were more resistant to ethanol‐induced hepatic steatosis and transaminase activity than the wild‐type mice, suggesting CYP2E1 contributes to ethanol‐induced toxicity. Metabolomic analysis of urinary metabolites revealed time‐ and dose‐dependent changes in the chemical composition of urine. N‐acetyltaurine (NAT) was identified as a urinary metabolite that is highly responsive to ethanol exposure. Stable isotope labelling analysis determined that NAT, with its acetyl group originated from ethanol metabolites, is a novel metabolite of ethanol, and NAT biosynthesis during ethanol treatment is contributed by both endogenous metabolism and ethanol metabolism. In vitro incubation assays showed that both acetyl‐CoA and acetate can react with taurine to form NAT. However, the enzymatic reaction between taurine and acetate is much more relevant to the metabolite concentrations in vivo than the reaction between taurine and acetyl‐CoA, indicating the former reaction is the main route of NAT biosynthesis in vivo. Furthermore, the contribution of acetate to NAT biosynthesis was confirmed by the immediate presence and increase of deuterated NAT after feeding deuterated acetate. The incubations of tissues and cellular fractions with taurine and acetate indicated that the kidney has the highest NAT synthase activity among tested organs while the cytosol is the main site of NAT biosynthesis inside the cell. Overall, the combination of biochemical and metabolomic analysis revealed NAT is a novel metabolite of ethanol and a potential biomarker of hyperacetatemia.Grant Funding Source: UMN startup fund for Chi Chen
Increasing the number of masticatory cycles reduces appetite and modulates glycemic response and plasma gut hormone concentrations
Authors: ZHU YONG , HSU WALTER H , HOLLIS JAMES H 
Published: June 2021

Eating slowly and chewing thoroughly are often recommended for weight management. However, few laboratory studies have been conducted to support this specific eating behavior as a means to control appetite. In a randomized cross‐over study, 21 healthy males consumed a fixed amount of pizza meal, by chewing each portion either 15 or 40 times before swallowing. Chewing rate was kept constant thus eating rate was slower in the 40 chews condition. Subjective appetite was measured by appetite questionnaires for three hours after meal, and plasma samples were collected for measurement of appetite‐related hormones and glucose. An ad libitum meal was served three hours later and the amount eaten measured. Compared with 15 chews condition, eating slowly by chewing 40 times per portion resulted in lower hunger (P=0.009), lower preoccupation with food (P=0.005) and lower desire to eat (P=0.002). Meanwhile, higher plasma level of glucose (P=0.024), insulin (P<0.001), gastric inhibitory polypeptide (P<0.001) and cholecystokinin (P=0.045) were observed with lower plasma level of ghrelin (P=0.051) following the 40 chews condition. However, the food intake at the subsequent meal did not differ. The results suggest eating slowly by increasing masticatory cycles could reduce postprandial appetite and may be a potential strategy for body weight management.Grant Funding Source: Iowa State University
Effect of masticatory cycles on postprandial appetite and subsequent food intake in seniors
Authors: ZHU YONG , HSU WALTER H , HOLLIS JAMES H 
Published: June 2021

Seniors are a population at the increased risk of inadequate food intake. It is not clear how appetite and postprandial metabolism are influenced in this age group by change in the number of masticatory cycles during ingestion. In a randomized cross‐over study, 15 senior males consumed a fixed amount pizza meal, by chewing each portion 15 or 40 times before swallowing. Appetite questionnaires and plasma samples were collected at regular intervals over three hours following meal consumption. An ad libitum meal was provided three hours later and the amount eaten measured. Compared to 15 chews, making 40 chews per portion resulted in lower hunger (P<0.001), lower preoccupation with food (P<0.001) and lower desire to eat (P<0.001). Higher levels of plasma glucose, insulin and gastric inhibitory polypeptide were found immediately following the 40 chews (P<0.05), but they became significantly lower later (P<0.05). No effect on cholecystokinin and ghrelin was found. There was a trend toward significant reduction in food intake at the subsequent meal following the 15 chews condition (P=0.066). The results suggest that increasing the number of chews promotes postprandial satiety in senior males but also paradoxically promotes food intake at the subsequent meal. The impaired control of food intake in seniors and different glycemic responses under different chewing conditions may partly explain for the results.Grant Funding Source: Iowa State University
High resolution carotenoid separations of serum and natural products using UHPLC
Authors: Craft Neal E. 
Published: June 2021

Carotenoids have been measured using HPLC with pressures up to 6000 psi for nearly 35 years. Recently, UHPLC, offering pressures up to 18,000 psi, has become readily available. These high pressures permit the use of <2um particle packings to produce very high efficiencies and rapid separations. Alternatively, UHPLC can be used to produce much higher resolution separations of carotenoids. Currently few sub‐2um column packings are available.ObjectiveTo compare several commercial columns and mobile phase combinations to determine the separation efficiency and selectivity using UHPLC and establish high resolution separations.ResultsA good HPLC separation with a 3um column produces about 20,000 theoretical plates. Multiple UHPLC columns were used in series to achieve unique selectivity and nearly 50,000 plates. The data from carotenoid standards was used to predict elution of other carotenoids and choose conditions for high resolution separations. Selected conditions were used to separate carotenoids in serum and natural products.ConclusionsUHPLC was successfully used in high‐resolution mode to achieve separations previously unattainable with conventional HPLC.
Ferroportin1 in hepatocytes and macrophages mediates systemic iron homeostasis
Authors: Zhang Zhuzhen , Zhang Fan , Guo Xin , An Peng , Tao Yunlong , Wang Fudi 
Published: June 2021

The liver is a major site for iron storage, but hepatocyte iron efflux mechanisms are unclear. To examine the hypothesis that Ferroportin1 (Fpn1) is a critical iron exporter in hepatocytes and macrophages, we generated both hepatocyte‐specific Fpn1 deletion mice (Fpn1Alb/Alb), and mice that lacked Fpn1 in hepatocytes and macrophages (Fpn1Alb/Alb;LysM/LysM). When fed a standard diet, Fpn1Alb/Albmice showed mild hepatocyte iron retention. However, RBC and hemoglobin levels were normal, indicating intact erythropoiesis. When fed an iron‐deficient diet, Fpn1Alb/Albmice showed impaired liver iron mobilization and anemia, with much lower RBC and hemoglobin, indicating that erythropoiesis depended upon both iron storage and iron demand status. Thus Fpn1 is critical for hepatocyte iron release. On standard diet, Fpn1Alb/Alb;LysM/LysM mice displayed substantially increased iron retention with intact erythropoiesis implying compensatory intestinal iron absorption. When fed an iron‐deficient diet, as iron mobilization from hepatocytes and iron recycling from macrophages were impaired, Fpn1Alb/Alb;LysM/LysM mice showed severe iron‐deficiency anemia regardless of their iron store status. Our data reveal new insights into the relationship among Fpn1‐mediated iron mobilization, iron storage, and iron absorption as these factors interact to maintain systemic iron homeostasis.Grant Funding Source: MOST of China (#2009CB941400, 2011CB966200); NSFC of China (# 10979071, 30970665, 31030039)
Cardiovascular risk factors are related to vitamin D status in midlife and older African Americans
Authors: Lemacks Jennifer Lynn , Ernst Jasminka Ilich , Ralston Penny A. , Young-Clark Iris , Coccia Catherine , Wickrama Kandauda , Harris Cynthia M. 
Published: June 2021

Some epidemiological studies suggest that CVD risk factors are negatively related to vitamin D status. The evidence is not clear and is sparse in African Americans (AAs) who are already at higher risk for CVD and have lower vitamin D status. Our objective was to examine the relationship between CVD risk factors and vitamin D status in midlife/older AAs enrolled in a church‐based health intervention project. 71 participants (73% women) had following mean±SD values: age 59.5±10.1y; BMI 34.9±9.2kg/m2; serum vitamin D (25OHD) 56.6±31nmol/L. 50% participants were vitamin D deficient/inadequate based on IOM's classification (serum 25OHD≤50nmol/L). Participants were divided into inadequate (IND) or adequate (ADD) vitamin D status groups and independent t‐tests revealed ADD had significantly lower BMI (31.5 vs 36.3kg/m2) and LDL (111.6 vs 126.1mg/dL) compared to IND. There were no significant differences in triglycerides, TotalChol, VLDL, HDL and blood pressure between groups. Separate regression models, controlled for age, gender, season, BMI, PTH and calcium/protein intake, showed negative influence of LDL, TotalChol, and ApoB/ApoA and positive of HDL on 25OHD. Based on these results, some CVD risk factors and markers of obesity are negatively related to vitamin D, strengthening the importance of higher vitamin D status in this population. NIH Institute on Minority Health & Health Disparities (R24MD002807‐02)Grant Funding Source : NIH
Bioavailability and Brain Deposition of Proanthocyanidin (PAC), Anthocyanin and Flavonoid in Combi‐Phenol Treated Rats on High Fat (HF) or Low Fat (LF) Diet
Authors: Chen Tzu-Ying , Janle Elsa , Ferruzzi Mario , Weaver Connie , Simon James , Wu Qingli , Talcott Stephen , Marambaud Philippe , Wang Jun , Ho Lap , Pasinetti Giulio M. 
Published: June 2021

Consumption of grape derived polyphenols is associated with the prevention of neurodegenerative diseases such as Alzheimer's disease (AD). HF diet, on the other hand, has been shown to be a risk factor on AD onset and progression. To further understand the physiological impact of these compounds ingested as a grape polyphenolic preparation termed ‘Combi‐Phenol’ and the influence of dietary fat on absorption and metabolism of PAC monomer, flavonoid, and anthocyanin, studies were conducted with Sprague‐Dawley rat fed on HF or LF diet. Rats were divided into four groups: LF‐control, HF‐control, LF‐Combi‐Phenol, HF‐Combi‐Phenol and fed on individual diet for 2 weeks prior to Combi‐Phenol treatment. Plasma pharmacokinetics was determined after dosing of Combi‐Phenol or water for 10 days. LC‐MS/MS analysis showed that glucuronide and methylated glucuronide are the main metabolites for (epi)catechin, quercetin, and resveratrol. Glucosides were the major derivatives for anthocyanins present in plasma and brains following Combi‐Phenol consumption regardless fat content in the diet. These data illustrate that dietary fat content did not affect the bioavailability of Combi‐Phenol and their access to the brain was also not influenced.Supported by NIH Grant: P01AT004511Grant Funding Source: NIH
Retinaldehyde‐Mediated Lipolysis Underlay Sexual Dimorphism in Visceral Obesity in Mice
Authors: Yasmeen Rumana , Reichert Barbara , Duester Gregg , Ziouzenkova Ouliana 
Published: June 2021

Increased risk of mortality in men and women is associated with the development of visceral fat that occurs in a sex‐specific manner by poorly understood mechanisms. Vitamin A metabolites: retinaldehyde (Rald) and retinoic acid (RA) are known to regulate key biological processes. Here, we explored the role of Rald and RA in sex‐specific fat formation, in a mouse model deficient in Aldh1a1, a major RA‐producing enzyme in white adipose tissue. The Aldh1a1−/− mice displayed a lean phenotype compared to wild type (WT), even on a high‐fat (HF) diet (300days). While subcutaneous fat remained similar in WT males and females, it was reduced in the Aldh1a1−/− mice. Strikingly, only Aldh1a1−/− females had significant reduction in visceral fat mass (12.3‐fold lower than WT females), while visceral fat reduction in Aldh1a1−/− males was insignificant (2.3‐fold) compared to WT males. We found markedly higher protein levels (compared to WT) of adipose triglyceride lipase (Atgl) in Aldh1a1−/− females vs. males. Consistant with Atgl's key role in lipolysis, visceral fat in Aldh1a1−/− female, but not male mice has Atgl‐positive staining in clusters of multilocular cells, also co‐expressing thermogenic proteins. The effective induction of Atgl protein levels was proven to be mediated by Rald. Altogether, our data suggest that Aldh1 could be a crucial target for treating female visceral obesity.Grant Funding Source : The EHE SEED Grant, The Ohio State University
Is mass cytological cancer screening possible worldwide?
Authors: Markovic Olivera , Markovic Nenad 
Published: June 2021

Our answer is yes, but with appropriate tools.Although preventable, cervical cancer is still, second to the breast cancer, major killer of women from malignant diseases worldwide. The outreach for preventive cytological screening is less than 10% in the most of the developing counties. Screening for risk factors such as HPV have contributed, but still not sufficiently.At EB 2004, we presented for the first time our proprietary, biomarker‐based MarkPap® platform technology. The biomarker is cytoplasmic expression of genetic changes in cervical cells during transformation from normal to pre‐malignant (dysplastic) and malignant. At subsequent EB meetings, we presented further developments of this technology from manual to semi‐automated, to diagnosis at distance‐telecytopathology (both digital and wireless), including home self‐collection. Most recently, we made self‐collection kit. With all these small devices, a low‐trained technician at the POC in remote sites, can process the specimen with customer‐friendly MarkPap® kit, locate suspicious cells by the biomarker and transmit microscopic images of those cells via MarkPap® Digital networking system to expert sites for instant diagnosis. Our recent testing with China and India proved that this concept is feasible.Consequently, development of low‐cost devices for mass cervical cancer screening for developing countries is warranted. .
Novel treatment of bladder cancer with cell therapy
Authors: Jeong Christina , Luria Ayala , Nolta Jan , Kurzrock Eric 
Published: June 2021

Our laboratory is studying a potential treatment for transitional cell carcinoma by developing a safe technique for the de‐epithelialization of murine bladder, evaluating aspects of spontaneous native urothelial regeneration, and determining the efficiency of cell replacement therapy. All techniques were performed on cadaveric mice. The mice were catheterized, and their bladders were distended by injecting 0%, 1%, 2%, or 4% trypsin for different periods of time ranging between 30 – 90 minutes at 37°C. Bladders were fixed and stained with hemotoxylin and eosin for histological analysis. The treatments with 1% trypsin had no apparent effect on the epithelial layer. With 2% trypsin, the epithelial cells start to detach leaving patches of urothelium on the basement membrane. Treating the bladder with 4% trypsin for 90 minutes completely removes the epithelial layer with the basement membrane still intact. Our results confirmed that 2% and 4% trypsin treatments can achieve different levels of de‐epithelialization in cadaveric mice. The results will be used as guidelines as we perform the same techniques in vivo. Subsequently, an analysis of cell regeneration and oncogenic‐free urothelium replacement will be done. By applying these tissue engineering technologies to human cancer models in the future, we can offer an entirely new approach to treat bladder cancer.UC Davis Cancer Center Developmental Awards
Cocaine dose and self‐administration history, but not initial cocaine‐induced locomotor responsiveness, affect sensitization to the motivational effects of cocaine in rats
Authors: Mandt Bruce H , Gomez Emily , Johnston Nickie L , Zahniser Nancy R , Allen Richard M 
Published: June 2021

Cocaine addiction is a significant and complex disease. Part of this complexity is due to variability of the drug experience early in drug use (e.g., initial responsiveness, amount of use, etc.). In rats, individual differences in initial cocaine responsiveness and cocaine self‐administration history both predict the development of cocaine sensitization, a putative mechanism contributing to addiction. Here we sought to determine the role of these factors and cocaine dose on the development of sensitization to cocaine's motivational effects during the earliest stages of self‐administration. Rats were classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on acute cocaine‐induced locomotor activity (10 mg/kg, IP) before learning to self‐administer cocaine (0.75 mg/kg/IV inf) under a fixed ratio 1 (FR1) schedule. Following acquisition, rats advanced to progressive ratio (PR) testing (0.75 or 1.5 mg/kg/inf cocaine) either immediately or after an additional 5 FR1 sessions (0.75 or 1.5 mg/kg/inf cocaine). No LCR/HCR differences were found. However, exposure to the higher dose of cocaine under both schedules produced sensitization to cocaine's motivational effects (i.e., increased break points). Thus, our results reveal the development of sensitization during the earliest stages of drug self‐administration and suggest this process may occur very early in drug addiction.This work was supported by NIH Grants R01 DA004216 and K05 DA015050 and an ASPET SURF award.
Role of Central Atypical Cannabinoid Receptor GPR18 in Modulating Cardiovascular Function
Authors: Penumarti Anusha , Abdel-Rahman Abdel A 
Published: June 2021

Background and objectivesThe abnormal cannabidiol (Abn CBD) receptor GPR18 mediates peripheral vasodilatation. N‐arachidonoyl glycine (NAGly) is the endogenous ligand of GPR18. Despite NAGly's abundance in the CNS and GPR18 mediated peripheral vasodilation, there are no studies on the role of central GPR18 in blood pressure control. Therefore, we investigated if GPR18 is: (i) present in the brainstem cardiovascular regulatory nuclei, particularly in presympathetic tyrosine hydroxylase (TH) expressing neurons; (ii) co‐expressed with Cannabinoid 1 receptors (CB1R) in those neurons and, (iii) the impact of GPR18 activation and blockade on blood pressure (BP) and heart rate.Key resultsOur immunofluorescence studies demonstrated GPR18 expression in the rostral vento‐lateral medulla (RVLM). GPR18 is co‐localized with TH expressing neurons as well as with CB1R in RVLM neurons. Intra‐RVLM microinjection in conscious male Sprague Dawley rats demonstrated dose‐dependent reduction in BP following GPR18 activation with Abn CBD. By contrast, intra‐RVLM blockade of GPR18 with the antagonist O‐1918 caused increase in BP and abrogated the Abn CBD‐evoked reduction in BP.ConclusionsThe present studies are the first to demonstrate the expression of GPR18 in the RVLM and to suggest a role for this receptor in modulating central cardiovascular functions.
The Role of Alternative Polyadenylation in Mediating Stress‐ Induced Protein Expression of Hsp70.3
Authors: Tranter Michael , McGuinness Michael , Helsley Robert N , Paulding Waltke R , Brokamp Cole , Haar Lauren , Ren Xiaoping , Jones W. Keith 
Published: June 2021

Heat shock protein 70.3 (Hsp70.3) expression is increased in response to cellular stress and plays a cytoprotective role. It has been shown that increased expression of Hsp70.3 expression in the heart is protective against ischemia/reperfusion injury. Recent work from our lab shows that Hsp70.3 expresssion is controlled through coordinated post‐transcriptional regulation by miRNAs and alternative polyadenylation (APA).Results show an APA‐mediated shortening of the Hsp70.3 3’‐UTR upon a stress‐induced increase in expression that facilitates increased protein expression during stress‐induced upregulation of the gene product. This work investigated the mechanisms through which APA‐mediated shortening of the 3’‐UTR contributes to increased protein expression. Our results describe the role of APA on mRNA stability and longevity, micro‐RNA regulation of Hsp70.3, and the role of APA on polysome loading and translational efficiency of the Hsp70.3 transcript.Our results provide a mechanistic understanding of the role APA plays in regulation of Hsp70.3 gene expression and have broad implications for the understanding of APA as a global modulator of gene expression.This work was supported by NIH RO1 HL0901478 (WKJ) and NIH T32 HL007382 (MT).