bluuebunny/crossref_metadata_2025_split huggingface dataset:
The C‐mannosyltransferase
Authors: Bakker Hans , Buettner Falk F.R. , Ashikov Angel 
Published: June 2021

C‐mannosylation of tryptophan residues occurs on proteins containing the consensus sequence WXXW, particularly thrombospondin repeat containing proteins and type I cytokine receptors. Mutagenesis of the WXXW motif in different proteins had already established important roles of this motif, suggesting that protein C‐mannosylation is as vital as N‐or O‐glycosylation. However, the genetic base of the enzyme catalyzing C‐mannosylation was so far not known.We identified C. elegans DPY‐19 as a protein with low sequence identity to the enzyme responsible for N‐glycosylation (oligosaccharyltransferase, OST). Homology is mainly based on identical overall membrane topology. Few amino acids are conserved, but three of these have been suggested to be involved in lipid linked donor‐substrate recognition of OST.We demonstrated that DPY‐19 is a C‐mannosyltransferase. Interestingly, the gene encoding DPY‐19 has long been known from a mutant presenting a defect in neuroblast migration. We showed that the dpy‐19 mutant is devoid of C‐mannosyltransferase activity. Moreover, by recombinant expression of DPY‐19 and mass spectrometric analysis, we could show C‐mannosylation of target proteins such as UNC‐5 and MIG‐21. Remarkably, dpy‐19 and mig‐21 mutants present identical phenotypes in neuroblast migration. Thus, our work showing C‐mannosylation of MIG‐21 by DPY‐19 provides a functional link between both mutants.
Regulation of Gene Expression by Short Poly‐N‐Acetyl Glucosamine (sNAG) Nanofibers in Endothelial Cells and Keratinocytes
Authors: Vournakis John , Amemiya Yutaka , Bacopulos Stephanie , Zhang Aiguo , Muise‐Helmericks Robin , Demcheva Marina , Seth Arun 
Published: June 2021

O‐GlcNAcylation is a catalyzed transfer of N‐acetylglucosamine to protein substrates. This modification aids cells in regulation of many crucial cellular processes. Short poly poly‐N‐acetyl glucosamine nanofibers (sNAG) enhance wound healing, by cell migration, and hemostasis, by promoting fibrin matrix and clot formation.This study investigated the effects of sNAG on global gene expression using the SOLiD 5500xl Next generation sequencing system in both HUVEC (Human Umbilical Vein Endothelial Cells) and HaCaT (Human keratinocytes) focussing on those having roles in angiogenesis and wound healing.In HUVEC cells, 1,705 genes had at least 2‐fold up‐or down‐regulation upon sNAG treatment. Genes which remained up‐regulated at both 1 and 6 hours of treatment were NFKBIZ, defensins and wound heaIing responses. Many of the collagen family of proteins, E‐Selectin, ICAM1, and cytokines, CXCL1 and CCL2, were up‐regulated transiently.In HaCaT cells, 2,329 genes showed 2‐fold up regulation in response to sNAG (1 or 6 hours) and 2,487 genes showed 2‐fold down regulation. Genes that were up‐regulated over the 6 hour treatment include desmogleins and keratins, suggesting regulation of keratinocyte differentiation and re‐epithelialization.Responses to sNAG observed in this study add support to its role in angiogenesis and wound healing pathways at the level of regulation of gene expression.
Osteoglycin (OGN) modulates inflammation during viral myocarditis via an interaction with Toll Like Receptor 4.
Authors: Rienks Marieke , Papageorgiou Anna Pia , Verhesen Wouter , van Leeuwen Rick , Carai Paolo , Westermann Dirk , Heymans Stephane 
Published: June 2021

BackgroundSmall leucine rich proteoglycans, like OGN, present in the extracellular matrix, have been described to interact with collagen and soluble growth factors, thereby modifying the extracellular milieu. Not much is known however about their influence on inflammation, therefore we investigated the role of OGN in viral myocarditis.ResultsIn both humans and mice with viral myocarditis, we demonstrated increased expression of OGN. We showed distinct OGN protein footprints in different murine cardiovascular disease models, with, a of 72kDa variant most abundant in viral myocarditis. After treatment with chondroitinase ABC there was a shift in detected size indicating the attachment of chondroitin sulfate to OGN. The 72kDa OGN co‐immunoprecipitated with TLR4. Lastly, stimulation of bone marrow derived macrophages with LPS demonstrated a decrease in cytokine production, in the presence of OGN.ConclusionWe demonstrated for the first time that variants of OGN are present in different cardiomyopathies. We showed that the OGN variant abundant in viral myocarditis had the glycosaminoglycan chondroitin sulfate attached to it, and that this variant bound to TLR4, hence modulate the response of macrophages to LPS. Understanding this mechanism and identifying the biochemical substrates responsible for this interaction, could lead to much needed new therapies for viral myocarditis.
HYALURONAN SYNTHESIS IS REGULATED BY INTRACELLULAR O‐GLCNACYLATION OF HAS 2
Authors: Passi alberto , Deleonibus Sara , Vigetti Davide , Viola Manuela , Karousou Evgenia , De luca Giancarlo 
Published: June 2021

The amount of hyaluronan (HA) often reflects the progression of the diseases involving extracellular matrix (ECM) as it promotes neo‐angiogenesis, cell migration and inflammation and its synthesis is regulated by several factors as the phosphorylation of synthetic enzyme HAS2. In this work, based on human smooth muscle cell model, we studied the intracellular regulation of HA synthesis at molecular level. The hexosamine biosynthetic pathway (HBP) may increase the concentration of HA precursor UDP‐Nacetylglucosamine leading to an increase of HA synthesis.We found that the inhibition of O‐GlcNacylation strongly reduced HA production whereas treatments that induced protein O‐GlcNacylation increased HA secretion. Gene expression studies done by quantitative RT‐PCR revealed that HAS2 mRNA was the most sensible to O‐GlcNacylation and accumulated after its induction. We found that the transcription regulator YY1 activates HAS2 expression after O‐GlcNacylation. Using IP and recombinant 6myc‐HAS2 we demonstrate the HAS2 residue O‐GlcNacylated and we quantified AoSMCs motility and monocytes binding and found that O‐GlcNacylation increased cell invasion and inflammatory cell recruitment. Moreover, using ChIP/sec approach we demonstrated that the O‐GlcNacylation is an epigenetic modification of protein interacting with HAS2 promoter.
Potential SET protein involvement in autophagy in cancer
Authors: Ouchida Amanda Tomie , Uyemura Valéria Tudella , Leopoldino Andréia Machado , Curti Carlos 
Published: June 2021

Autophagy is a process by which lysosomes degrade and recycle long‐lived proteins and cellular organelles. It degrades cellular components that are worn out/damaged or needed to generate substrates to maintain cellular energy homeostasis under conditions of limited nutrients or stress. Cells of squamous cell cancer of the head and neck (HNSCC), which is the fifth most common malignancy in the world, have a high expression of the SET protein and under oxidative stress they perform the autophagic process. Therefore, the aim of our study is to verify a potential involvement of the SET protein on the autophagic process in these cells exposed to oxidative stress. Initially, knockdown of the SET protein (siSET) was performed in the Cal 27 cell line, in which oxidative stress was induced with tert‐butylhydroperoxide (t‐BHP). Proteins involved in autophagy as LC3B, Beclin‐1 and p62 were analyzed by immunoblotting. The siSET in Cal 27 cells caused an increase in the level of these proteins, which was slightly and significantly reduced after 4 and 8 hours of exposure to t‐BHP, respectively. Acids vacuoles identified by immunofluorescence, which are indicative of autophagy, were also found in Cal 27 cells for siSET and treatment with t‐BHP. Therefore, we believed that SET protein is important for the modulation of autophagy in HNSCC. PCR array assays are now in progress in order to assess potential genes involved in this regulation.FAPESP and CAPES
Suppression of Scopolamine‐induced Cognitive Impairment by Dehydroglyasperin C
Authors: Kim Jong‐Sang , Seo Ji Yeon , Park In Sil , Kim Seong Soon , Kang Hye Ryung , Kim Bo Ram , Zakharova Alexandra , Kim Hyo Jung 
Published: June 2021

Our previous study demonstrated that dehydroglyasperin C (DGC) isolated from licorice had neuroprotective effects in mouse hippocampal cells. This study was conducted to assess the protective effect of DGC on the impairment of memory and cognitive function in scopolamine‐treated mice. ICR mice (5 week‐old, male) were injected i.p. with 1 mg/kg body weight of scopolamine to induce amnesia. The ability of learning memory of mice was evaluated by passive avoidance test. The spatial learning and memory abilities of mice were assessed by Y‐maze test and Morris water maze test. We found that DGC improved the cognitive function of mice injected with scopolamine in a dose‐dependent manner. In particular, the group treated with 10 mg DGC/kg body weight showed the longer latency time than the control group. Moreover, DGC suppressed the scopolamine‐induced spatial memory impairment as assessed by Y‐maze test. The inhibitory activity of DGC against acetylcholine esterase present in hippocampus and cortex extracts was also observed. In conclusion, these results suggest that DGC attenuates scopolamine‐induced memory impairment maybe through enhancement of the cholinergic nervous system via acetylcholinesterase inhibition.Grant Funding Source: National Research Foundation of Korea
Adequacy of the intake of vitamins and mineral in women participants in the Mexican National Nutrition Survey 2006 (ENSANUT‐2006)
Authors: Villalpando Salvador , Ramirez‐Silva Ivonne , Moreno‐Saracho Jessica , Shamah‐Levy Teresa , Beltran‐Velázquez Filiberto , Campos‐Vega Rocio 
Published: June 2021

ObjectiveTo evaluate the adequacy of intake of micronutrients and fiber in women from the ENSANUT‐2006.MethodsDietary intake and compliance with dietary recommendations were estimates for a sample of Mexican women aged >;19 years from ENSANUT‐2006. Food intake came from a food frequency questionnaire. Dietary adequacy was classified into adequate (adequacy >;100%), moderately inadequate (50–99%), and highly inadequate (<50%).AnalysisMeans of adequacy were estimated through linear and polynomial multiple regression.ResultsThe adequacy for vitamin A varied by age from 69–79%, the following intakes decreased progressively with age: Vitamin C 69–50%, folate 26–12.4%, vitamin B12 56.4–34.4%. For minerals iron decreased from 21.2–12‐13% and increased to 45% in >;50 years of age. Calcium increased with age from 24.9–32.9% and declined to 15.0%. Magnesium intake decreased from 56.6–36.9% and phosphate increased from 57.8–88.2%. The adequacy for fiber increased with age from 12–36%.DiscussionWe documented evidence about the low dietary intake of vitamins and minerals prevailing in Mexican women, although the coincidence with the prevalence of micronutrients deficiencies only occurred with vitamins A and C, calcium, magnesium.
Long‐term effects of micronutrient supplementation on school age child behavior
Authors: Bahnfleth C–arlotte Lena , Murray‐Kolb Laura E , Schaefer Barbara , Cole Pamela , Katz Joanne , Khatry Subarna K , LeClerq Steven , Tielsch James M , Christian Parul 
Published: June 2021

Data on long‐term effects of preschool micronutrient supplementation on behavior are sparse. We examined behavior in 7–9 y old Nepali children (n=694) who received micronutrient supplements from 12–35 mo of age in a double‐masked RCT. Children were randomized to daily iron‐folic acid (IFA); zinc (Zn); iron‐folic acid+zinc (IFAZn); placebo (PL). Behavior was assessed on six dimensions (positive mood; negative mood; lively/active; sociability; sustained attention; demandingness) during two visits. Differences in behavioral ratings were examined relative to the PL for each supplement group. Additionally, those who received any zinc (Zn or IFAZn) or iron (IFA or IFAZn) were compared to those who did not. Overall, those who received IFA scored higher in sustained attention (p=0.05) and demandingness (p=0.02) and those who received IFAZn scored higher in sociability (p=0.04) compared to PL. After adjusting for confounders, the only difference remaining was higher demandingness scores in those who received IFA compared to PL (p=0.002). In both unadjusted and adjusted analyses, children who had received zinc vs. not were rated significantly higher in sociability (p=0.0007 and p=0.009, respectively), but no differences were found between those who received iron vs. not. Zinc supplementation between 12–35 mo appears to have a positive effect on sociability at 7–9 y.Grant Funding Source: NICHD and Gates Foundation
Iron deficiency but not anemia affects cognition in Indian adolescents
Authors: Scott Samuel , Murray‐Kolb Laura , Wenger Michael , Udipi Shobha , Ghugre Padmini , Haas Jere 
Published: June 2021

A quarter of the world's population is thought to be deficient in iron. Though the functional effects of iron deficiency have been studied in infancy and adulthood, adolescence, a period of significant neural and behavioral maturation, has not received much attention. In this cross‐sectional analysis of Indian adolescents in rural Maharashtra (n = 147; 12–16 y; 61 females), relations between baseline blood variables and performance on a test of simple reaction time (SRT, in ms, one of a set of five measures of perceptual and cognitive functioning) were examined. Iron status was defined according to stage of iron deficiency (iron‐deficient anemic (IDA), iron‐deficient (ID), iron sufficient (IS)). Those in the IDA and ID groups had longer RT than those in the IS group (p=0.005 & 0.013, respectively). SRT for individuals who were anemic but not ID did not differ from those of the IS group but were faster than those in the IDA and ID groups (both p<0.01). Further analyses revealed that the serum ferritin quartile was strongly related to SRT (p<0.001) whereas hemoglobin quartile was not. Finally, those with positive body iron (calculated by Cook's equation) had shorter SRTs than those with negative body iron (p=0.044). We conclude that iron deficiency with or without anemia is associated with slower responding, whereas anemia in the absence of iron deficiency is unrelated to response speed in Indian adolescents.Grant Funding Source: HarvestPlus
Prospective, Randomized Double Blind Study to Test Vitamin A Treatment in Patients with Sepsis
Authors: Tayek John A 
Published: June 2021

PurposeTo test the benefits of Vitamin A Tx patients with sepsis on length of time in ICU, Days on Ventilator, Days on Pressors and 28‐day mortality. The trial was prospective, randomized and double‐blind. As part of a larger sepsis trial, 63 patients with sepsis were randomized to receive either 50,000 IU of Vitamin A intramuscular or placebo over 7‐days. Data analysis was by ANOVA with two tailed test and p<0.05 as significant.ResultsThe mean age was 51+2 (mean+ SEM) with 54% female. All patients had an ACTH stimulation test using 250 mcg of ACTH IV and serum cortisol was measured at time 0, 30 and 60 minutes. Baseline cortisol of 24.6+1 mg/dl increased to 41+2 mg/dl at 30 minutes and 49+2 at 60 minutes. There was no significant difference between the groups. All cortisol responses were greater than 12.9 mg/dl. Serum Vitamin A level was below normal in 54% of the patients tested (n=35). Table 1 describes the two groups with regard to baseline APACHE III score, baseline WBC and percent of patients with bacteremia. Vitamin A was given to 32 patients and placebo was given to 31 patients.ConclusionsThe number of days in the ICU was slightly, but not significantly (p=0.13), reduced in Vitamin A treated patients. The average number of days on pressors, the number of days on the ventilator and the 28‐day mortality rate were also not significantly different. Vitamin A Tx in septic adult patients failed to significantly reduce the number of days in the ICU, days on the ventilator, days on pressor agents or 28‐day mortality. Seven days of high dose Vitamin A Tx has no benefit in adults with sepsis (mean+sem).
What role does moderate alcoholic beverage intake play in cardiovascular health?
Authors: Pourafshar Shirin , Johnson Sarah A. , Jafarinasabian Pegah , Bonn Mark , Arjmandi Bahram H. 
Published: June 2021

Cardiovascular disease is the number one cause of death in the United States. Red wine consumption has been promoted for its positive effects on high‐density lipoprotein cholesterol; however, the effects of moderate and heavy alcoholic beverage consumption on cardiovascular health remain unclear. The objective of this cross‐sectional study is to investigate the role of alcoholic beverage intake on cardiovascular health. A total of 60 men and women aged 25 to 40 years old with a body mass index (BMI) between 18.5 and 35 will be included. Participants will be divided into seven quartiles (never or less than 1 drink per week, 1 drink per week, 2–3 drinks per week, 4–6 drinks per week, 1 drink per day, 2+ drinks per day, and 3+ drinks per day) based on their alcoholic beverage intake as indicated in the Beverage Questionnaires. Overnight fasting blood measurements will include C‐reactive protein and lipid profiles. Atherogenic risk ratios, waist‐to‐hip ratio, and BMI will be calculated. Body composition will be assessed using dual‐energy X‐ray. Seated blood pressure (BP) will be assessed by measuring resting brachial BP. Pearson correlation coefficients will be used to determine the relationship between variables of interest. The findings of this study will further our understanding of the role of alcoholic beverage consumption in cardiovascular health.Grant Funding Source: Dedman School of Hospitality
Association of an AHA‐diet quality score with allostatic load and metabolic syndrome in Puerto Rican adults
Authors: Mattei Josiemer , Bhupathiraju Shilpa , Tucker Katherine L 
Published: June 2021

A score based on diet and lifestyle guidelines from the American Heart Association (AHA) has been associated with cardiovascular risk factors in Puerto Ricans. We aimed to assess whether the diet components alone were associated with metabolic syndrome (MetS) and allostatic load (AL) as a composite measure of ten dysregulated physiological parameters. The diet quality score (range: 0–90) included components on intake of dietary fats, fruits and vegetables, whole grains, salt, added sugars, and alcohol, and was tested on 1318 Puerto Ricans (45–75 y/o; 72% female) living in Boston, MA. Mean (SD) diet score was 28.0 (9.9) for males and 30.0 (10.1) for females. Significant inverse associations between diet score and cortisol, waist circumference, and plasma insulin, and positive association with DHEA‐S, were observed in females. In males, the score was inversely associated with norepinephrine and positively with HDL‐C (all p<0.05). In multinomial logistic regression, an increase in 10 units of AHA‐diet score was associated with 22% (95%CI: 1, 39%; p=0.039) lower odds of having ≥ 6 AL components in females, compared to ≤ 2 parameters. In males, lower odds of MetS were observed for a 10‐ unit increase in diet score (0.71 (0.53, 0.96), p=0.027). In conclusion, following a high‐quality diet recommended by the AHA may help maintain cardiometabolic risk factors under control and reduce likelihood of MetS and AL in Puerto Ricans.Grant Funding Source: Supported by NIH grants P01 AG023394 and P50 HL105185
Consistencies in the quality of meals vs. snacks reflect biomarkers of health risks in US adults
Authors: Shin Dayeon , Song Won O. 
Published: June 2021

Health risks are affected by the combination of meals and snacks that differ in compositions and frequencies. We tested the hypothesis that inconsistent qualities of meals vs. snacks are measurable health risks (FBS, insulin, HgA1c, TG, LDLC, TChol; adiposity). Dietary recall data of 2238 men and 2305 women (≥20y) in NHANES 2007–8 were assessed for the quality of meals and snacks separately using HEI‐2005. The HEI scores for snacks(X) and meals(Y) were divided into 2×2 quadrants(Q) by mean HEI scores (51.0 vs. 38.0, resp.): left lower Q (LLQ), right lower Q(RLQ), 3) left upper Q (LUQ) and 4) right upper Q (RUQ). The associations between 4Qs and health risk factors were tested by Chi‐Square and Anova using SAS 9.3. Inconsistent quality of meals and snacks (RLQ and LUQ) accounted 45% of US adults and 47–48% of high income and educated groups. Women, ≥college educated, Hispanics were likely to be in RUQ, which was lower in Kcal, sat fat, sodium and alcohol, and higher in fiber (p<0.05). High quality snacks (RUQ, RLQ) were high in protein, fiber and low alcohol. Lower adiposity were in RUQ; higher TG in LLQ; higher BMI, sodium and alcohol in RLQ. We conclude that 45% of US adults have snacking patterns inconsistent with their usual meal patterns, leading to potential change in health risk factors.Grant Funding Source: Nestle USA
Timing of infant swallowing within the respiratory cycle during breastfeeding
Authors: Geddes Donna Tracy , Stoddart Rohanna , Sakalidis Vanessa , Hartmann Peter Edwin 
Published: June 2021

During feeding, the infant must briefly cease respiration during swallowing. This can occur mid expiration (EE), mid inspiration (II), between inspiration and expiration (EI) or the opposite (IE). When the majority of swallows (60–75%) are followed by expiration this is considered a mature pattern. Since milk flow rates are highly variable during breastfeeding we hypothesized that the frequency of EE and IE swallows would not comprise the majority of swallows. Simultaneous measurements of infant tongue movement, intra‐oral pressure, swallowing and breathing were made for a breastfeed in 10 infants (mean age: 47 days; range 18 – 115). For nutritive sucking (NS) the most frequent phase of respiration for a swallow was EE (median %; interquartile range, 35; 18–53) and EI (33; 11–49) followed by IE (10; 0–21) and II (4; 0–18). There was no difference in frequency for EE and EI however EE occurred more often than IE and I‐I (P<0.01). Less than half of the NS swallows were followed by expiration. Preliminary results suggest a predominance of swallows followed by expiration do not necessarily represent a mature swallowing pattern in breastfed infants and the ability to swallow in response to variable flow rates may contribute to breastfeeding success.Funding: an unrestricted research grant from Medela AG