bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell polarity kinase MST4 cooperates with cAMP‐dependent kinase to orchestrate histamine‐stimulated acid secretion in gastric parietal cells
Authors: JIANG HAO , Wang Wenwen , Zhang Yin , Yao William W. , Ding Xia , Liu Xing , Yao Xuebiao 
Published: November 2023

The digestive function of the stomach depends on acidification of the gastric lumen. Acid secretion into the lumen is triggered by activation of PKA cascade, which ultimately results in the insertion of gastric H, K‐ATPases into the apical plasma membranes of parietal cells. A coupling protein is ezrin whose phosphorylation at Ser66 by PKA is required for parietal cell activation. However, little is known regarding the molecular mechanism(s) by which this signaling pathway operates in gastric acid secretion. Here we show PKA cooperates with MST4 to orchestrate histamine‐elicited acid secretion by phosphorylating ezrin at Ser66 and Thr567, respectively. Histamine stimulation activates PKA which phosphorylates MST4 at Thr178 and then promotes MST4 kinase activity. Interestingly, activated MST4 then phosphorylates ezrin pre‐phosphorylated by PKA. Importantly, MST4 is important for acid secretion in parietal cells because either suppression of MST4 or overexpression of non‐phosphorylatable MST4 prevents the apical membrane reorganization and proton pump translocation elicited by histamine stimulation. In addition, overexpressing MST4 phosphorylation‐deficient ezrin results in an inhibition of gastric acid secretion. Taken together, these results define a novel molecular mechanism linking PKA‐MST4‐ezrin signaling cascade to polarized epithelial secretion in gastric parietal cells.Support or Funding InformationThis work was supported by Chinese 973 Project 2013CB911203; Ministry of Education 20113402130010; Anhui Project 08040102005; Chinese Natural Science Foundation Grants 31430054, 31271518, 31301105, 90508002 and 90913016; National Institutes of Health Grants CA164133 and DK56292; China Postdoctoral Science Foundation Grant 2014M560517; and Central University Grants WK2340000032 and WK2340000021.
Transcriptome Profiling of Burkholderia thailandensis Reveals that MftR is a Master Regulator
Authors: Gupta Ashish , Wang Guannan , Dassanayake Maheshi , Grove Anne 
Published: November 2023

The Burkholderia thailandensis‐encoded major facilitator transport regulator (MftR) is a multiple antibiotic resistance regulator (MarR) homolog. mftR is divergently oriented to a gene encoding major facilitator transport protein (MftP), which is a major facilitator superfamily efflux pump. The mftR‐mftP locus is conserved in B. cenocepacia, which is a serious pathogen of patients with cystic fibrosis. Biofilm formation by this bacterium makes it less sensitive to antibiotics, making infection by B. cenocepacia difficult to treat. To combat the bacterial infection, the host produces reactive oxygen species (ROS), and one enzyme involved in this process is xanthine oxidase, which also produces urate. The invading pathogen may therefore detect urate and respond by upregulating the expression of virulence genes. MftR responds to urate by upregulation of mftR and mftP. To see the global effect of urate on B. thailandensis and the effect of MftR, we carried out transcriptome sequencing (RNA‐seq) analyses of wild type (WT) and mftRΔ cells grown in absence and presence of urate. The analysis of RNA‐seq data shows that ~330 genes are differentially expressed (>2‐fold) in the presence of urate and that MftR regulates ~310 genes. In mftRΔ and in WT grown in presence of urate, some genes are either up‐ or downregulated compared to WT, consistent with MftR controlling expression. For example, both mftRΔ and urate upregulate genes encoding enzymes responsible for the synthesis of 2‐heptyl‐4‐quinolone (HHQ). This signaling quinolone participates in cell‐cell communication. Genes encoding type III secretion system are repressed in mftRΔ and with urate. Some genes are differentially regulated by urate and not by MftR, suggesting the existence of additional factors that respond to urate; urate upregulates the whole flagellar gene cluster in the mftRΔ strain. Flagella play a vital role in biofilm formation and host invasion. Taken together, our data suggest that the urate‐responsive MftR is a master regulator that controls expression of genes associated with host colonization later in infection.Support or Funding InformationNIH grant (1R15GM107825) to Anne Grove
Biochemical characterization of the substrate specificity of two unique members of the mammalian protein arginine methyltransferase family, PRMT7 and PRMT9
Authors: Hadjikyriacou Andrea , Feng You , Yang Yanzhong , Bedford Mark T. , Clarke Steven G. 
Published: November 2023

Protein arginine methylation is a widespread and important posttranslational modification in eukaryotic cells, shown to be involved in the activation or repression of transcription, modification of the splicing machinery, signaling, and DNA repair. Mammalian protein arginine methyltransferases include a family of nine sequence‐related enzymes that transfer one or two methyl groups onto the terminal guanidino groups on arginine residues, producing monomethylarginine only (MMA, type III), symmetric dimethylarginine (SDMA) and MMA (Type II), or asymmetric dimethylarginine (ADMA) and MMA (Type I). While PRMT1, 2, 3, 4, 6, and 8 have been characterized as type I enzymes, and PRMT5 as a type II enzyme, the role and activity types of the two final members of this family of enzymes, PRMT7 and PRMT9, had been unclear due to conflicting results in the literature, and the substrates for these enzymes had been elusive. Both PRMT7 and PRMT9 are distinct members of the family with two methyltransferase or methyltransferase‐like domains and containing acidic residues in otherwise well‐conserved substrate double E binding motif, features not seen in the other PRMT enzymes. Recent work in our laboratory confirmed PRMT7 as the only type III MMA‐forming enzyme in the group, with a unusual low temperature optimum for activity, and a heretofore not seen preference for a basic stretch of residues in an R‐X‐R sequence for methylation. Mutations of the acidic residues in the substrate‐binding motif results in a loss of the specific R‐X‐R activity and the appearance of a G‐R‐G specificity typical of many of the other PRMTs. The physiological substrate of PRMT7 has yet to be confirmed, although histone H2B is an effective in vitro substrate. PRMT9, on the other hand, had no reported activity, until immunoprecipitation from HeLa cells showed it pulled down two splicing factors, SF3B2 and SF3B4, in a complex. Amino acid analysis showed that PRMT9 methylates SF3B2 to produce both MMA and SDMA, thus making it the second type II enzyme in mammals. PRMT9 knockdown results in modulation of alternative splicing events. This enzyme appears to be relatively specific for the SF3B2 protein; a peptide containing the methylatable arginine residue was not found to be a substrate, and typical substrates of other PRMTs are not recognized by PRMT9. We found that the position of the methylated arginine residue in SF3B2 is important, and the acidic residues in the substrate‐binding motif also play an important role in substrate recognition. Thus, PRMT7 and PRMT9 represent unique members of the mammalian PRMT family.Support or Funding InformationNIH grants GM026020 to S.G.C., DK062248 to M.T.B. and GM007185, a Ruth L. Kirschstein National Research Service Award to A.H.
Use of Dietary Scores for Diet Quality Measurement: Relation with Nutritional Status of Women in Northern Benin
Authors: Burney Jennifer , Alaofe Halimatou , Naylor Rosamond , Taren Douglas 
Published: November 2023

BackgroundDietary diversity is recommended to obtain good nutritional status and health. However, the association between the diversity score and nutritional status of women is unknown in Benin.ObjectivesThis study's purpose was to assess dietary diversity and its relationship to the nutritional status of women of childbearing age.MethodsIn 2014, a total of 680 mothers with children below the age of 5 y were recruited from 16 villages in Kalalé district of Northern Benin. Dietary diversity scores (DDS) were assessed based on frequency of consumption of individual food items categorized into 12 individual food groups. These scores were then divided into tertile. Body mass index (BMI) was used to determine the women's nutritional status.ResultsThe overall dietary quality was poor: mean DDS=5.6 (SD 1.4) food groups. Approximately 24% consumed 7 or more food groups and 9.3% consumed less than 4 food groups. Considering the diet within each category of the diversity score, women with low scores had a very basic diet and consumed only three food groups (cereals, condiments and oils/fats) at most. Women with medium scores often consumed vegetables, roots and tubers in addition to these groups, and also a little more meat, fish, legumes, nuts or seeds, and sugar. Women who had higher dietary diversity scores also ate more meat, fish, legumes, nuts or seeds, sugar as well as some fruits. Women with a DDS in the lowest tertile had a mean BMI of 20.9, while those in the highest tertile had a BMI of 22.4 (P=0.042). Those in the lowest tertile of DDS had a 15.8% prevalence of underweight vs 6.3% in the highest tertile (P=0.02). The latter relationship remained significant even when the subjects’ sociodemographic and economic characteristics were controlled (P=0.04).ConclusionDietary scores measured at the individual level were a good proxy for overall dietary quality of women living in northern Benin. These scores were also shown to be linked with the nutritional status of women indicating that dietary diversity of women can also be measured to obtain information on their nutritional status.
Implantation of Insulin‐producing Cells From Human Umbilical Cord Blood Mesenchymal Stem Cells in The Liver and Its Potential to Cure Streptozotocin‐induced Diabetes: An Animal Model Study
Authors: Eladl Mohamed Ahmed , El‐Sherbiny Mohamed , Ranade Anu Vinod , Gabr Hala 
Published: November 2023

BackgroundDiabetes mellitus (DM) is one of the most prevalent chronic diseases affecting people globally. To date, researchers are still in search for new therapeutic measures that could further improve patients conditions. The aim of this study was to investigate the therapeutic response to injected human umbilical cord blood mesenchymal stem cells (HUCBMSC) in Streptozotocin (STZ) induced diabetic albino rats.Materials and MethodsThe present study was conducted on three groups of albino rats. The first group (GI, n=25), was the control group in which rats were fed with standard rat diet, Group II and III (n= 25 each) were STZ‐induced diabetic albino rats with and without differentiated HUCBMSC stem cell implantation respectively. Animals were sacrificed on the eleventh week following implantation, and liver biopsies were collected. In addition to hematoxylin and eosin (H&E), liver sections were stained with Prussian blue as well as immunostain using anti‐ human insulin antibodies in order to highlight both the presence and function of the impregnated cells in the liver tissue.ResultsThe H&E stained sections of the rats in GI and GII showed normal liver architecture while animals of GIII showed the presence of cell clusters inside the liver tissue and around central veins. Blue cell clusters were absent in animals of GI and GII when stained with Prussian blue. However, these cell clusters with blue cytoplasm were present in sections from GIII indicating the presence of injected differentiated UCBMSCs (Photomicrograph 1). The sections with antihuman insulin immunostaining of GIII showed clusters of cells within the liver parenchyma and around the central veins indicating that these cells are active and secreting insulin (Graph 1), while there were no such cells found inside the liver parenchyma of GI and GII (Photomicrograph 2).ConclusionHuman UCBMSCs are capable of differentiating into insulin‐secreting cells (IPCs) in vivo when transplanted into the liver of STZ‐induced diabetic albino rats. They were able to secrete insulin and partially control the diabetic status of the rats. However, further research is needed in the field of human UCBMSCs, in the hope that it might be a promising source with potential therapeutic application in diabetics.
Autism Linked to Alcohol and Sugar Intake
Authors: Shamberger Raymond Joseph 
Published: November 2023

The rate of autism is increasing 10–15% per year. The cause of autism is unknown. Autism usually appears in children ages 2 to 4. Because one cannot follow the usual nutrition over several years, nutritional epidemiology was applied from two sources. The Institute of Health Metrics and Evaluation at the University of Washington published a study “Where America Drinks”. They have determined the percentage of alcohol consumed in every county of the United States except Hawaii and Alaska. In addition to the counties, an average intake was calculated for each state. They divided the alcohol consumption to one drink or less per month and the other to more than one drink per month. They also published an average amount of alcohol per state. This result was correlated to the amounts of autism among 8 year olds per state. The autism and alcohol consumption correlated r=0.519 and p<0.001. Horizontal trend lines were found for many of the states (45–48).Alcohol consumption was also compared to multiple sclerosis among war veterans r=0.610 and p<0.0001. Horizontal trend lines between the alcohol curve and those with multiple sclerosis were also found (40–48).The USDA has measured the B‐vitamin content of human breast milk from 279 mothers, After calculating the average amount that the babies drink, comparisons can be made to the MDR (Minimal Daily Requirement). With the exclusive breast feeding that is recommended for the first six months it is possible that there could be a B‐vitamin deficiency, All of the B‐vitamins were acceptable except thiamine which was well below the MDR for the first four months. Part of this deficiency can credited to the excess sugar intake in America, Thiamine is needed for the first step of the Krebs cycle and excess sugar could cause a thiamine deficiency. Thiamine is also decreased by alcohol.Support or Funding InformationNo funding or support.
Sugary beverage and food consumption and leukocyte telomere length maintenance in pregnant women: a pilot study
Authors: Leung Cindy W , Laraia Barbara A , Coleman‐Phox Kimberly , Bush Nicole R , Lin Jue , Blackburn Elizabeth H , Adler Nancy E , Epel Elissa S 
Published: November 2023

Leukocyte telomere length (LTL) has been inversely associated with sugar‐sweetened beverage (SSB) consumption in cross‐sectional studies, but its relation to other sources of added sugars is unknown. Furthermore, no studies have examined whether dietary intake influences LTL over time. This study examined longitudinal associations between sugary foods and beverages and LTL. Participants were 65 overweight and obese pregnant women, aged 18–45, in an 8‐week mindfulness intervention study conducted in early pregnancy (≤16 weeks gestation) with follow up through 9 months postpartum. During the pregnancy and postpartum periods, dietary intake was measured with two 24‐hour diet recalls and LTL was assessed using quantitative polymerase chain reaction. From baseline to 9 months postpartum, increased consumption of SSBs was associated with greater concurrent LTL shortening (β= −0.094, 95% CI −0.171, −0.016), adjusting for sociodemographic and health characteristics. No associations were observed between the intakes of sugary foods, including dairy desserts, sweetened yogurt, baked goods, candy, and syrups and sweet sauces, and changes in LTL. The association between SSB consumption and LTL shortening warrants investigation in large prospective cohort studies.Support or Funding InformationThis study was supported by the National Institutes of Health grants (U01 HL097973 and K99 HD084758 to C.W. Leung).
Relation of Total Sugars and Fructose‐Containing Sugars with Risk of Cardiovascular Disease: A Systematic Review and Meta‐Analysis of Prospective Cohort Studies
Authors: Khan Tauseef Ahmad , Blanco‐Mejia Sonia , de Souza Russell , Kendall Cyril WC , Sievenpiper John L 
Published: November 2023

ObjectiveIntake of sugars‐sweetened beverages has been associated with weight gain and risk of cardiovascular disease in adults, though, it is not known if the intake of total sugars and particularly fructose‐containing sugars is associated with cardiovascular disease (CVD). We undertook a systematic review and meta‐analysis of cohort studies to quantify the relation of total sugars, sucrose, and fructose with incident CVD.MethodsMEDLINE, EMBASE and Cochrane Library (through October 31, 2015) were searched for relevant studies. We included prospective cohort studies in humans investigating the association between total and individual fructose‐containing sugars and incident CVD. Two independent reviewers reviewed and extracted the relevant data and assessed study quality (Newcastle‐Ottawa Scale). Risk estimates of extreme comparisons (lowest versus highest quantile) were pooled using inverse variance random effects models and expressed as risk ratios (RR) with 95% confidence intervals (CIs). Inter‐study heterogeneity was assessed with Cochran Q statistic and quantified with the I2 statistic.ResultsEight prospective cohort comparisons (n = 512,343) involving 14,035 cases of CVD observed over an average of 11.9 years of follow‐up were eligible. Median total sugar intake was 55 g and 115 g in the lowest and highest quantile respectively. Total sugars intake was weakly associated with increased CVD risk (RR, 1.08 [95% CIs, 1.01 to 1.14]) with no evidence of heterogeneity (I2= 0%, p= 0.99). There was a weak positive association with total fructose intake (RR, 1.08 [95% CIs, 1.00 to 1.15]) but not total sucrose intake (RR, 0.95 [95% CIs, 0.87 to 1.04]) with no evidence of significant heterogeneity (I2<29%, P>0.24). Effect estimates were similar when stratified by sex.LimitationsAs the observed associations were weak and the 95% CIs for sucrose included potentially important benefit, measured and unmeasured residual confounding cannot be excluded.ConclusionsTotal sugars and fructose were weakly associated with increased CVD risk in eight large prospective cohort comparisons. Additional studies looking at important food sources of sugars other than sugars‐sweetened beverages may be helpful in better explaining the relationship between dietary sugars and CVD risk.Support or Funding InformationCanadian Diabetes Association and PSI Foundation. https://clinicaltrials.gov/ct2/show/NCT01608620
Despite higher n‐6 PUFAs, butter remains a reliable source of saturated fats across the world
Authors: GHOSH SANJOY , Botta Amy 
Published: November 2023

Recent epidemiological data and updated meta‐analyses indicates that the saturated fat from sources like butter is not harmful in appropriate quantities. However, anecdotal evidence suggests that commercial farming, with increased incorporation of linoleic acid [LA, an n‐6 polyunsaturated fatty acid (PUFA)] containing oilseeds in animal feeds enhances LA and depletes saturated fatty acids (SFA) in animal food sources like butter. However, concrete evidence is lacking. We hypothesized that across the world, n‐6 PUFA content in butter would be inversely proportional to SFA content and directly proportional to country‐wide n‐6 PUFA rich oilseed production rates. We analyzed fatty acid compositions of commercial table butter from 7 countries (USA, Canada, Japan, Australia, India, France and the Netherlands) via gas chromatography. A locally sourced butter from a grass‐fed cow was used as a reference. Rates of oilseed production in those countries were collected from the FAOStat 2012 database. Unsurprisingly, all commercial butter contained higher n‐6 and lower beneficial n‐3 PUFA than grass‐fed butter, except in Dutch butter where both were high. However, contrary to our hypothesis, LA content of butter was not reflective of oilseed production rates across countries. Moreover, instead of depleting SFA, LA levels were directly proportional to SFA in butter, with the highest present in Canadian butter. As, the increase of LA in commercial butter compared to our grass fed sample was only 1.17% of total fatty acids, we conclude that the issue of higher n‐6 PUFAs is minor and butter continues to be a reliable source of SFA (72–73% of all fatty acids) across the world.Support or Funding InformationDairy Farmers of Canada
MODELLING SUBSTITUTION OF FOODS. A TOOL TO IMPROVE DIET QUALITY
Authors: Weill Ricardo Julián , Zapata María Elisa , Domet Marine , Clerfeuille Edouard , Carmuega Esteban 
Published: November 2023

IntroductionArgentinean population has low intake of calcium and dairy products. Food surveys available in the country and CESNI studies show that 68% of adults do not reach a consumption of 2 servings daily and that calcium intake decreases with age at 5 year‐old as a consequence of a reduction in the amount of dairy servings consumed. This reduction results in a high proportion of individuals with calcium intakes below recommendations (from 26% of preschoolers to 74% of elderly population). In order to effectively address these insufficiencies, the challenge is to provide acceptable and potentially impactful dietary advice best suited to the eating habits of these populations. In order to capture these habits, complex statistical tools are required in particular to take into account the dynamics of consumption, associations and substitutions in real dietary practices.MethodologyA statistical tool was developed to determine the associations and substitutabilities of different foods and beverages in actual eating and drinking practices. Using food and drink consumption data from a 7‐day diary run on a representative sample 18‐ to 69‐year‐old Argentinian urban women, the level of substitutability is estimated as a function of amount, frequency and moment of consumption, at the individual and population level. Simulation analyses were then performed using Creme Food® software, in order to measure the potential impact on nutrient intakes of virtually substituting a given food or beverage for its main alternatives, in corresponding proportions.ResultsOur analyses show that in adult urban Argentinian women, dairy consumption could be potentially increased by replacing 23.8% of the infusions, 25.96% of cookies, and 18.1% of crackers at breakfast by fresh dairy products; or replacing 24.4% of the infusions, 25.3% of bakeries and pastries, 22.6% of crackers, and 18.15% of cookies at mid‐afternoon snacking by fresh dairy products.If these substitutions were performed with a yogurt low in sugar and fat and fortified in calcium, our simulation analyses show that the consumption of free sugars would decrease by 10% while total and saturated fat would remain stable and calcium intake would double, with prevalence of intakes below requirements shifting from 64% to 11%.ConclusionThis tool applied on representative samples of the population may be useful to design realistic scenarios for potential changes in dietary patterns and their impact on nutrient intakes.Support or Funding InformationDanone Nutricia Research