bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased expression of ER stress genes in patients with limited cutaneous Systemic Sclerosis and Pulmonary Arterial Hypertension
Authors: Lenna stefania , Farina Alessandra G , Martyanov Viktor , Christmann Romy B , Wood Tammara A , Faber Harrison W , Scorza Raffaella , Whitfield Michael L , Lafyatis Robert , Trojanowska Maria
Published: June 2021

Objective

Previous studies have implicated ER stress and UPR in autoimmune and inflammatory diseases.The goal of this study was to assess whether markers of ER stress/UPR are present in PBMCs from limited cutaneous systemic sclerosis (lcSSc) patients with pulmonary arterial hypertension (PAH).

Methods

PBMCs were purified from healthy controls (HC n=36) and lcSSc patients (n=38 with PAH and n=39 without PAH).Gene expression in HC PBMCs stimulated with ER stress inducer, thapsigargin (TG) was analyzed by DNA microarray.Expression levels of select ER stress/UPR genes and inflammation genes were analyzed by qPCR.

Results

ER stress/UPR genes, including BiP, transcription factors ATF4 and ATF6, and a spliced form of XBP1 were upregulated in lcSSc PBMCs, with the highest levels in patients with PAH.TG induced expression of HSPs and IFN‐regulated genes in control PBMCs.Selected HSP genes, particularly DNAJB1, and IFN‐related genes were significantly elevated in lcSSc PBMCs.There was a positive correlation between DNAJB1 and severity of PAH disease (PAP) (r = 0.59, p<0.05) and between BiP and IL‐6 levels (r = 0.64, p< 0.0001) in lcSSc PBMCs.

Conclusion

These studies demonstrate a possible association between ER stress/UPR gene activation and lcSSc‐PAH suggesting that ER stress/UPR contribute to the interferon signature and altered function of circulating immune cells in patients with lcSSc.
Myeloid Depletion of SOCS3 Enhances LPS‐Induced Acute Lung Injury through CCAAT/Enhancer Binding Protein delta Pathway
Authors: Gao Hongwei , Yan Chunguang , Wang Ximo
Published: June 2021

Objective

SOCS3 is an important negative regulator of IL‐6‐type cytokine signaling. SOCS3 is induced in lung during LPS‐induced lung injury. The objective of this study is to test the hypothesis that SOCS3 is a critical regulator of LPS‐induced ALI.

Methods

We created mice lacking SOCS3 expression in macrophages and neutrophils (LysM‐cre SOCS3fl/fl). We evaluated the lung inflammatory response to LPS in both LysM‐cre SOCS3fl/fl mice and the wild type mice (SOCS3fl/fl). We also determined the role of CCAAT/enhancer‐binding proteins (C/EBP)β and ‐δ in LPS‐induced ALI by using C/EBPβ and ‐δ mutant mice.

Results

LysM‐cre SOCS3fl/fl mice displayed significant increase of the lung permeability index (lung vascular leak of albumin), lung neutrophil accumulation (MPO activity), neutrophils and proinflammatory cytokines/chemokines in bronchial alveolar lavage (BAL) fluids compared to wild‐type mice. These phenotypes were consistent with morphological evaluation of lung, which showed enhanced inflammatory cell influx and intra‐alveolar hemorrhage. We further identify C/EBPδ, but not C/EBPβ, as a critical downstream mediator of SOCS3 in LPS‐induced ALI.

Conclusions

Results indicate that SOCS3 has a protective role in LPS‐induced ALI by suppressing C/EBPδ activity in the lung. Elucidating the function of SOCS3 and C/EBPδ would represent prospective targets for a new generation of drugs needed to treat ALI.
Marine Pharmacology and the Marine Pharmaceuticals Pipeline
Authors: Mayer Alejandro MS , Glaser Keith B
Published: June 2021

As the renaissance in the pharmacology of marine natural products continues (Glaser and Mayer, Biochemical Pharmacology 78:440–448, 2009), the purpose of this project was to assess the status of the clinical marine pharmaceuticals pipeline. Results were the following: there were five FDA‐approved marine‐derived drugs in the US market, namely cytarabine for cancer (Cytosar‐U®, Depocyt®, FDA‐approved 1969), ziconotide for pain (Prialt®, FDA‐approved 2004), omega‐3‐acid ethyl esters for hypertriglyceridemia (Lovaza®, FDA‐approved 2004), eribulin mesylate for cancer (Halaven®, FDA‐approved 2010), brentuximab vedotin for cancer (Adcertis®, FDA‐approved 2011), while vidarabine as an antiviral (Vira‐A®, FDA‐approved 1976) was no longer available, and trabectedin for cancer (Yondelis®, FDA‐orphan drug approval 2005) being EU‐registered. The clinical marine pharmaceutical pipeline, recently reviewed (Mayer et al. TIPS 31:255–265, 2010), as of October 2012 consisted of 11 marine‐derived compounds in clinical development. These included three new monoclonal antibodies conjugated to synthetic dolastatin derivatives, that were in either Phase I, Phase II or Phase III clinical trials. Finally, the preclinical marine pharmacology pipeline remained a global enterprise with researchers from several countries reporting novel mechanisms of action for multiple marine chemicals (Mayer et al. Comparative Biochemistry and Physiology C 153: 191–222, 2011). We conclude that both marine pharmacology preclinical research as well as the clinical pharmaceutical pipeline remained very active in 2012. Supported by Midwestern University.
Higher blood pressure in 5‐ to 7‐year‐old children born preterm as compared to children born at term
Authors: Landmann Eva , Huke Verena , Brugger Markus , Strauch Konstantin , Berthold Lars Daniel , Rudloff Silvia
Published: June 2021

Premature birth which is associated with impaired pulmonary and renal function implies higher cardiovascular risk by developing elevated blood pressure early in life. In this study, systolic blood pressure (SBP) and diastolic blood pressure (DBP) was determined from 236 children aged 5 to 7 years, i.e., 116 children born preterm (gestational age 29.8 ± 2.6 (30; 24–33) weeks [mean ± SD (median; range)]) and 120 children born at term using an automated oscillometric device. Being born small‐for‐gestational age (SGA) was defined as birth weight < 10th percentile. All analyses were performed with in‐ and exclusion of children born SGA. Length‐adapted SBP and DBP were significantly higher in preterms compared to children born at term (p < 0.0001 and p < 0.0003, respectively). Multiple regression analyses including further variables with potential influence on blood pressure confirmed the independent association between prematurity and SBP and DBP. Being born preterm was associated with an increase in SBP by 3.2 mmHg (p=0.0022) and in DBP by 2.1 mmHg (p=0.0077). This study indicates blood pressure to be significantly higher after preterm birth as early as at the age of 5 to 7 years. Identifying mechanisms underlying higher blood pressure in individuals born preterm is crucial for developing preventive strategies.

[Supported by the German Research Foundation (DFG grant no. LA 2428/1–1)]
Fish oil and neurovascular reactivity to mental stress in humans
Authors: Carter Jason R. , Schwartz Christopher E. , Yang Huan , Joyner Michael J.
Published: June 2021

Omega‐3 fatty acids found in fish oil have been suggested to protect against cardiovascular disease, yet underlying mechanisms remain unclear. Given the well documented links between mental stress (MS) and cardiovascular risk, we hypothesized that fish oil would blunt blood pressure (BP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) responsiveness to MS. Neural and cardiovascular responses to a 5 min mental arithmetic protocol were recorded in 67 non‐hypertensive subjects before and after 8 wks of fish oil (9g/day; n=33) or placebo (olive oil; 9g/day; n=34). Fish oil blunted HR reactivity to MS (group × condition × time interaction, P=0.012), but did not alter BP reactivity (interactions, P>;0.05). Fish oil blunted total MSNA reactivity to MS (interaction, P=0.039), but did not alter MSNA burst frequency and burst incidence reactivity (interactions, P>;0.05). Finally, fish oil significantly blunted calf vascular conductance (CVC) reactivity to MS (interaction, P=0.013), but did not alter forearm vascular conductance reactivity (interaction, P>;0.05). In conclusion, 8 wks of fish oil supplementation significantly attenuated HR and total MSNA reactivity to MS, and elicited a paradoxical blunting of CVC. These findings support and extend the growing evidence that fish oil may have positive health benefits regarding neural cardiovascular control in humans. Supported by NIH (HL‐088689).
Cutaneous blood flow influences near infrared spectroscopy evaluation of frontal lobe oxygenation by approximately 30%
Authors: Sørensen Henrik , Kohl‐Bareis Matthias , Siebenmann Christoph , Zaar Morten , Hvidtfeldt Morten , Ogoh Shigehiko , Sato Kohei , Secher Niels Henry , Lundby Carsten , Rasmussen Peter
Published: June 2021

Frontal lobe cerebral oxygenation (scO2) is assessed by spatially resolved near infrared spectroscopy (SR‐NIRS) to exclude the contribution of extra‐cerebral tissue. However, changes in cutaneous blood flow impact scO2 but the contribution of the skin to scO2 is unknown. This study quantified the influence of cutaneous blood flow on scO2 in 22 healthy subjects exposed to whole‐body exercise in hypoxia (FiO2 = 12 %) and normoxia (n = 12), whole‐body heating, hyperventilation (n = 22), administration of noradrenaline with and without petCO2‐correction (n = 15), phenylephrine, and head‐up tilt (n = 7) while scO2 was assessed by NIRO‐200NX (sniroO2) (Hamamatsu, Japan) and INVOS‐5100 (sinvosO2) (Somanetics, Troy, MI). Arterial (saO2), skin (sskinO2), and jugular bulb saturations (sjO2) were obtained. Regression analysis indicated that sinvosO2 reflects 42% arterial, 32% jugular, and 26% skin oxygenation while for sniroO2 the values were 24%, 42%, 34%, respectively (all P < 0.0001). The results demonstrate that skin contributes about 30% to both systems’ evaluation of scO2.
Severe thermal trauma alters adipose tissue mitochondrial function in children
Authors: Porter Craig , Chondronikola Maria , Herndon David N , Børsheim Elisabet , Sidossis Labros S
Published: June 2021

Severe thermal trauma results in a hypermetabolic stress response. Whether altered mitochondrial function plays a role in this response remains unknown. Here, coupled and uncoupled mitochondrial O2 consumption rates (Mito‐VO2) were determined in subcutaneous adipose tissue (AT) samples obtained from healthy children and children with severe burns.

Maximal Mito‐VO2 was determined in Digitonin permeabilized subcutaneous AT samples from healthy children (7.8±2.3 years old, n=5), and children with severe burns (12.1±2.4 years old, 42±28 days post‐burn, 55±17% total body surface area burned, n=9) (mean±SD), in the presence of excess substrates (octanoyl‐carnitine, pyruvate, malate, glutamate, and succinate) and ADP. State 4 respiration was determined following the addition of oligomycin.

Mito‐VO2 was 2.5‐fold greater in AT samples from children with severe burns relative to healthy children (2.04±0.34 vs. 0.79±0.23 pmol/(mg*sec), P<0.05). In addition, AT state 4 respiration (when Mito‐VO2 is uncoupled from ATP production) was 5‐fold greater in severely burned children relative to healthy children (2.06±0.39 vs. 0.42±0.15 pmol/(mg*sec), P<0.05) (mean±SEM).

These data are the first to show that severe burn injury alters subcutaneous AT mitochondrial function; where mitochondria have a greater capacity for uncoupled respiration in patients with severe burns. This suggests that altered AT mitochondrial function may play a role in the hypermetabolic response to burn injury.

Supported by the National Institutes of Health grant P50‐GM60338 and Shriners Hospitals for Children grants 84090 and 84080.
PSD‐95 interacts with NBCn1 and enhances channel‐like activity without affecting cotransport function
Authors: Lee Soojung , Choi Inyeong
Published: June 2021

NBCn1 plays an essential role in intracellular pH regulation and transepithelial bicarbonate movement in the body. NBCn1 also has sodium channel‐like activity uncoupled to Na/HCO3 cotransport. We previously reported that NBCn1 interacts with the postsynaptic density protein PSD‐95 in the brain. Here, we elucidated the structural determinant and functional consequence of NBCn1/PSD‐95 interaction. In rat hippocampal CA3 neurons, NBCn1 was localized to the postsynaptic membranes of both dendritic shafts and spines and occasionally to the presynaptic membranes. A GST/NBCn1 fusion protein containing the C‐terminal 131 amino acids of NBCn1 pulled down PSD‐95 from rat brain lysates, whereas GST/NBCn1‐ΔETSL (deletion of the last four amino acids) and GST/NBCn2 lacking the same ETSL did not. NBCn1 and PSD‐95 were coimmunoprecipitated in HEK 293 cells. PSD‐95 has negligible effects on intracellular pH changes mediated by NBCn1 in HEK 293 cells and Xenopus oocytes. However, PSD‐95 increased an ionic conductance produced by NBCn1 channel‐like activity. This increase was abolished by NBCn1‐ΔETSL or by the peptide containing the last 15 amino acids of NBCn1. Our data suggest that PSD‐95 interacts with NBCn1 and increases its channel‐like activity while negligibly affecting Na/HCO3 cotransport. We propose that the channel‐like activity may occur via an intermolecular cavity of multimeric NBCn1 proteins.
KCNQ channels regulate activity of chemosensitive neurons in the retrotrapezoid nucleus
Authors: Hawryluk Joanna Monica , Wenker Ian C , Takakura Ana C , Moreira Thiago S , Tzingounis Anastasios V , Mulkey Daniel K
Published: June 2021

Chemosensitive neurons in the retrotrapezoid nucleus (RTN) regulate breathing in response to CO2/H+. Their activity is also sensitive to neuromodulatory inputs from other respiratory centers, thus serve as a nexus of respiratory control. However, the molecular mechanisms that control their activity and propensity to neuromodulation are unknown. Here we show in vitro and in vivo that KCNQ channels are critical determinants of RTN neural activity. In brainstem slices isolated from rat pups (P7–12), application of XE991 (selective KCNQ channel blocker) increased basal activity by 1.4 ± 0.2 Hz and decreased serotonin responsiveness by ~50%. While inhibition of SK channels with apamin had no effect on basal activity or serotonin‐sensitivity. Unexpectedly, neither XE991 nor apamin had any effect on other raphe transmitters. We show that blocking KCNQ channels in the RTN in vivo blunts the ventilatory response to serotonin in awake and anesthetized animals. Together, these results indicate that KCNQ channels: i) regulate tonic activity and serotoninergic modulation of RTN neurons in vitro; ii) are effectors of serotonin modulation of RTN in vivo; iii) and contribute to respiratory drive in anesthetized and awake animals. Given that 5‐HT dysfunction may contribute to respiratory failure, our findings suggest a new therapeutic avenue for respiratory complications associated with multiple neurological disorders.
Renal subcapsular infusion of siRNA as a novel method of gene silencing in the kidney
Authors: Asico Laureano D , Villar Van Anthony M , Escano Crisanto S , Yang Yu , Cuevas Santiago , Feranil Jun B , Armando Ines , Jose Pedro A
Published: June 2021

Transgenic and knockout technologies allowed the development of mouse lines for the functional analysis of genes on animal physiology. Classic gene knockout requires the deletion of a gene in ES cells and may result in embryonic lethality. Functional characterization in viable offspring may be confounded by the development of compensatory changes in utero. Innovative conditional knockouts allow the reversible gene silencing in a limited number of tissues; however, this technology is tedious and expensive, and is not always successful. As a viable alternative to these techniques, we tested the feasibility of using gene‐specific siRNA infused via an osmotic minipump into the subcapsular space of the kidney of uninephrectomized C57Bl/6J and BALB/cJ mice. A 7‐day siRNA infusion ensured optimum gene silencing without gross or histological changes in the renal parenchyma or spill over into other organ systems. At least 60% knockdown efficiency was observed for several genes tested, e.g., Snx1, DJ‐1, Pon2, Drd2, and Usp48, which are genes that regulate blood pressure (BP). These were accompanied by changes in systolic BP (ΔSBP=26±3 mm Hg for Snx1; 24±4, DJ‐1; 41±5, Pon2; 20±5, Drd2; −21±2, Usp48 [n=3–4/group]). Our novel subcapsular siRNA infusion offers the advantage of restricted gene silencing in one kidney only and precludes unforeseen compensatory mechanisms that may develop in classical knockout models.
Baby‐Friendly Hospital Practices and Birth Costs
Authors: Allen Jessica , Longenecker Holly B. , Perrine Cria G. , Scanlon Kelley S.
Published: June 2021

Objective

Describe the association between the number of breastfeeding supportive practices a hospital has in place and the cost of an uncomplicated birth.

Methods

Data from hospitals in 20 states that participated in the 2007 Maternity Practices in Infant Nutrition and Care (mPINC) survey and Healthcare Cost and Utilization Project's (HCUP) State Inpatient Databases (SID) were merged to calculate the average median hospital cost of uncomplicated vaginal and C‐section births by number of ideal practices indicating the Ten Steps to Successful Breastfeeding. Linear regression analyses were conducted to estimate change in birth cost for each additional ideal practice in place.

Results

Unadjusted analyses of uncomplicated births revealed a significant increase in the cost of C‐section births ($98) with each additional practice in place, but no significant increase in the cost of all births or vaginal births ($44 and $35, respectively). The adjusted model showed no significant difference in cost per additional practice among any of the birth groups (all births, $19; vaginal, $15; C‐section, $40).

Conclusions

Our results revealed that the number of breastfeeding supportive practices a hospital has in place are not significantly associated with higher birth costs. Concern for higher birth costs is not necessarily a barrier for improving maternity care practices that support women who choose to breastfeed.
High Amylose and Stearic Acid‐Modified Resistant Starch: Human Post‐Prandial Gut Fermentation and Blood Glucose Response
Authors: Haugabrooks Esther , Ai Yongfeng , Jane Jay‐lin , Hendrich Suzanne
Published: June 2021

Stearic acid‐modified digestion‐resistant starch was compared with its parent high amylose starch for physiological effects in healthy humans. In a randomized blinded crossover study after a 10‐h fast, 30 volunteers ate crackers providing 50 g carbohydrate and 10% (control starch, CS), 30% (high amylose, HA) and 50% (stearic acidRS5) digestion resistance as measured by AOAC method 991.43. Blood glucose and fermentation were tested. Participants consumed one cracker type as a test meal once a week over a period of 3 weeks. Blood glucose area under the curve (AUC) was not different between HA and RS5; both produced lesser AUC responses than CS (p < 0.05). Fermentation, assessed by breath hydrogen was greater after ingestion of RS5 than after eating HA or CS (p< 0.05). In vitro digestion of crackers by AOAC method 2000.02 corresponded with the in vivo glucose response to each starch. Overall gastrointestinal symptoms assessed from a questionnaire were minimal and not statistically different between cracker types. This study indicates that further study of health effects of the fermentability of RS5 should be feasible in humans. Research support received from AFRI Proj. no. 2009–65503‐05798.
Commensal Lactobacillus modulate ROS‐dependent cytoprotective gene expression in intestinal epithelia
Authors: St Clair Ardita Courtney , Jones Rheinallt M , Mercante Jeffrey W , Luo Liping , Gates Cymone , Moberg Keneth H , Neish Andrew S
Published: June 2021

A growing body of data has emerged showing that members of the gut microbiota are essential for the normal physiology and homeostasis of the intestine. However, the molecular basis for these processes are not well understood. In this study, we describe a novel role for the commensal bacterium Lactobacillus in intestinal cytoprotection. We show that this bacterial genus specifically induces cellular reactive oxygen species (ROS) in both Drosophila and murine guts. This ROS induction in turn stimulates the redox‐sensitive Nrf2 pathway and leads to consequent ARE (Antioxidant Response Element)‐dependent cytoprotective gene expression. Nrf2/ARE pathway mediated cytoprotection is well established in many tissues, but its stimulation by gut bacteria is completely unrecognized. Using Nrf2 knockout Drosophila and mice, we demonstrate that Nrf2 is required for protection against a variety of intestinal insults. Together, these data show that gut microbial stimulated ROS generation modulates the Nrf2 signaling pathway thus maintaining intestinal epithelial homeostasis and cytoprotection, and that this effect is evolutionarily conserved.
Neutrophil slow rolling and intravascular crawling is dependent on the guanine‐exchange factor P‐Rex1
Authors: Herter Jan Michael , Rossiant Jan , Block Helena , Stadtmann Anika , Welch Heidi , Zarbock Alexander
Published: June 2021

Integrin activation is a hallmark for the function of leukocytes and concise trafficking. Here, we investigated the role of P‐Rex1, a Rac‐specific guanine nucleotide exchanging factor, in integrin activation and leukocyte recruitment. We used intravital microscopy of the M. cremaster and the kidney cortex supplemented by in vitro assays of P‐Rex1 knock‐out mice to determine the role of P‐Rex1 in the different steps of leukocyte recruitment and assessed Rac1 activation in a GTP pulldown approach. Finally we subjected P‐Rex1−/− mice to a model of ischemia‐reperfusion induced acute kidney failure to assess physiological consequences of our findings. We report that P‐Rex1 is required for inducing selectin‐mediated LFA‐1 extension, which corresponds to the intermediate affinity conformation and induces slow leukocyte rolling, whereas P‐Rex1 is not involved in the induction of the high‐affinity conformation of LFA‐1 obligatory for leukocyte arrest. Furthermore, we demonstrate that P‐Rex1 is involved in Mac‐1‐dependent intravascular crawling. Mice deficient in P‐Rex1 are protected from ischemia‐reperfusion induced kidney failure.

This study was supported by grants from the German Research Foundation (AZ 428/3–1, AZ 428/6–1, SFB 1009/A5 to A.Z and HE‐6810/1–1 to J.H.).
Telomerase Holoenzyme Assembly
Authors: Collins Kathleen
Published: June 2021

Maintenance of the terminal telomeric repeat tracts requires new repeat synthesis by the specialized ribonucleoprotein reverse transcriptase telomerase. Reconstitution of telomerase enzyme activity in vitro requires the template‐containing telomerase RNA subunit (TER) and the telomerase reverse transcriptase protein (TERT). Numerous additional subunits coassemble or interact with the endogenously functional telomerase holoenzyme complex. Recent studies in the Collins laboratory have focused on defining the factors required for assembly and activity of telomerase holoenzyme using two model systems: the single‐celled ciliated protozoan Tetrahymena and cultured human cells. We have begun to elucidate the biochemical mechanisms that underlie unique features of the telomerase catalytic cycle such as the use of an internal RNA template and the processive synthesis of single‐stranded DNA repeats.
NIH Support of Pre‐ and Postdoctoral Training for a Career as a Research Scientist
Authors: Ulane Rod E.
Published: June 2021

Your pre‐ and postdoctoral training define you as a biomedical scientist and set the course for your career. NIH grant support is an important element in this process. This presentation will explain what NIH grants are available to graduate students, postdoctoral fellows, and those individuals transitioning to independent careers as scientists. The expectations and review of applicants and applications at each stage of training will be discussed. In addition, historical data will be presented on career outcomes of individuals supported by these awards, as well as the number of awards typically made, and the success rates of applicants.
Proteomic Analysis of Pol II Preinitiation Complexes: The Roles of Mediator and SAGA
Authors: Carey Michael
Published: June 2021

An important property of RNA polymerase II preinitiation complexes (PIC) is their ability to coordinate transcription initiation with chromatin modification and remodeling. We employed multidimensional protein identification technology (MuDPIT) to study the composition and assembly of PICs in HeLa and mouse embryonic stem (ES) cell nuclear extracts. Strikingly, most of the machinery necessary for transcription initiation on chromatin is part of the PIC. The PIC is nearly identical between ES and HeLa cells, and contains two major co‐activator complexes, Mediator and SAGA. Genomewide analysis of Mediator reveals a close correlation with Pol II, TBP and mRNA levels implying a major role in PIC assembly. Mechanistic analysis of the two co‐activators showed that they play distinct roles in PIC function. Mediator coordinates assembly of the Pol II initiation factors and chromatin machinery into a PIC, while SAGA acts after PIC assembly to allow transcription on chromatin. MuDPIT analysis of Mediator isolated from native chromatin, under conditions where the transcriptional machinery remains intact, suggests that PICs assembled in vitro and in vivo are similar.
Molecular Regulation of Protein O‐Glycosylation and Relevance to Disease and Development
Authors: Cummings Richard D. , Wang Yingchun , Ju Tongzhong
Published: June 2021

Altered glycan expression is a hallmark of animal development and cellular differentiation, as well as being a hallmark of cancer. A common class of glycans is the mucin‐type O‐glycan linked via GalNAcα1‐Ser/Thr, a precursor that is recognized as the Tn antigen and is normally extended to form complex O‐glycans. O‐GalNAc glycans occur in many cell surface glycoproteins. We discovered a key gene involved normal extension of O‐GalNAc glycans is the T‐synthase, which encodes a β1,3‐ galactosyltransferase that generates the common T‐antigen Galβ1–3GalNAcα1‐Ser/Thr. Unexpectedly, expression of the T‐synthase is under the control of a unique molecular chaperone termed Cosmc, which is a resident endoplasmic reticulum chaperone whose sole client is the T‐synthase. Cosmc is encoded by an X‐linked gene (Xq24) in humans; acquired or engineered acquired mutations in Cosmc lead to a loss of T‐synthase due to its misfolding and subsequent degradation, and concomitant expression of the Tn antigen in all cells. We have developed genetically engineered mice lacking Cosmc that express Tn antigen in a tissue‐ and cell‐specific manner. Our studies show that a wide variety of glycoproteins require extended O‐GalNAc glycans for normal expression and localization, oligomerization, turnover, and stability, and suggest a new paradigm for the functions of O‐GalNAc glycans in regulating a wide variety of cellular processes.
Weight, serum hepcidin, and iron status in pregnant African American women
Authors: Tussing‐Humphreys Lisa , White‐Traut Rosemary , Hennessy Mary Dawn
Published: June 2021

Iron is critical during pregnancy and deficiency is related to maternal and neonatal complications. Obesity is associated with iron deficiency and decreased dietary iron absorption likely resulting from inflammation‐related expression of the systemic iron regulator hepcidin. Although, one in two adult women of child‐bearing age are overweight or obese, few studies have examined the relationship between weight and maternal iron status and regulation during pregnancy. We conducted a pilot study with 24 African American women recruited in the second trimester and measured iron status, serum hepcidin, inflammation, body weight and other behavioral factors at 22 and 32 weeks gestation; prepregnancy BMI, height, and demographic data were also collected. Descriptive statistics, difference in serum values across BMI groups and Pearson's correlations between BMI and serum values were assessed. Based on pre‐pregnancy BMI, 5 women were normal weight, 7 overweight, and 12 obese; with mean age of 28. At 22 and 32 weeks gestation, serum iron was significantly lower in overweight and obese women and soluble transferrin receptor and hepcidin similar across BMI groups. Pre‐pregnancy BMI was significantly correlated with serum hepcidin (r=0.53) at 32 weeks gestation. Findings suggest maternal iron status may be impaired in overweight and obesity possibly through upregulation of hepcidin. Funding UIC CCTSS0811–02.
Quercetin encapsulated nanocarriers: effects on breast cancer cell growth, apoptosis, and uptake in vitro and bioavailability in vivo
Authors: Sun Ming , Nie Shufang , Pan Xuan , Fan Zhaoyang , Wang Shu
Published: June 2021

Background

Quercetin, a natural flavonoid, has a potential against many breast cancer cells, but its low solubility and bioavailability in the body make administering it in therapeutic dose unrealistic. We have successfully synthesized quercetin encapsulated nanocarriers (NanoQ). Our hypothesis is that NanoQ can enhance quercetin stability and solubility, increase quercetin bioavailability in vitro and in vivo, decrease the viability of breast cancer cells, and induce their apoptosis.

Methods

The stability, solubility and cellular uptake of quercetin in MCF7 and MDA‐MB‐231 breast cancer cells were measured using a high performance liquid chromatography system. The viability and apoptosis of breast cancer cells were measured using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and Annexin‐V/propidium iodide assay, respectively. The pharmacokinetics of NanoQ was measured in SD rats.

Results

NanoQ were about 30 nm in diameter. Nanoencapsulation significantly increased the stability and solubility of quercetin, and increased quercetin cellular content 3.9 times and 9.3 times in MCF7 and MDA‐MB‐231 cells, respectively. NanoQ also significantly lowered the viability of both breast cancer cells and induced their apoptosis as compared to free quercetin at the same concentrations.

Conclusion

NanoQ is a promising approach for the prevention and treatment of breast cancer.

Grant Funding Source: TTU research incentive funding
Effects of vitamin C and vitamin D on mood and distress in acutely hospitalized patients
Authors: Wang Yifan , Liu Xing Jian , Robitaille Line , Eintracht Shaun , MacNamara Elizabeth , Hoffer L John
Published: June 2021

Hypovitaminosis C and D are highly prevalent in acute‐care hospitals, but their clinical implications have not been investigated. Because deficiencies of these vitamins can adversely affect mood, we conducted a double‐blind randomized clinical trial to determine the effect of vitamin C (500 mg twice daily) or D (5000 IU daily) supplementation on psychological status, as assessed using two different validated instruments. At baseline, 73% of patients had a subnormal plasma vitamin C concentration (< 28.4 μM) and 79% had a subnormal plasma 25OHD concentration (< 75 nM). Vitamin C provision for a mean of 8.2 days (n = 26) normalized plasma vitamin C concentrations (P < 0.0001) and resulted in a 71% reduction in Profile of Mood StatesR total mood disturbance score (from 24.0 ± 18.2 to 6.9 ± 14.4, mean ± SD; P = 0.0002) and a 51% reduction in psychological distress as measured using the Distress Thermometer (from 4.5 ± 2.9 to 2.2 ± 2.2; P = 0.0002). By contrast, high‐dose vitamin D provision for a mean of 8.1 days (n = 26) increased plasma 25OHD concentrations (P < 0.0001), but not into the normal range, and had statistically insignificant effects on mood (21.7 ± 17.3 to 14.6 ± 17.7; P = 0.067) and distress (3.7 ± 2.6 to 3.4 ± 2.8; P = 0.45).

Conclusion

Hypovitaminosis C and D are highly prevalent in acutely hospitalized patients. Vitamin C supplementation improves mood and reduces distress in these patients. Supported by the Lotte and John Hecht Foundation and a Faculty of Medicine student research bursary.

Grant Funding Source: Lotte and John Hecht Foundation
DUSP1 gene polymorphisms are associated with obesityrelated metabolic complications and gene methylation levels in severely obese patients
Authors: Guénard Frédéric , Bouchard Luigi , Tchernof André , Deshaies Yves , Hould Frédéric‐Simon , Lebel Stéfane , Marceau Picard , Vohl Marie‐Claude
Published: June 2021

DUSP1 is a member of the dual‐specificity phosphatase family involved in the regulation of innate immune function and inflammation. In a previous study, DUSP1 gene was found to be underexpressed in visceral adipose tissue from severely obese men with the metabolic syndrome.

Objective

To verify the association between DUSP1 polymorphisms, gene expression and methylation levels and obesity‐related metabolic complications.

Methods

Association of tagging SNPs (tSNPs) with obesity‐related complications was tested in a cohort of 1900 severely obese individuals. Impact of tSNPs on CpG site methylation and correlations between DNA methylation and gene expression were computed in a subset of 14 samples.

Results

Following adjustment for the effects of age, sex and BMI, heterozygotes for rs881150 had lower HDL‐cholesterol levels and homozygotes for rs13184134 and rs7702178 had increased fasting glucose levels. rs13184134 was associated with methylation levels of CpG sites located ~1800 bp upstream the transcription start site. Methylation levels for 3 CpG sites located in this region were inversely correlated with DUSP1 gene expression.

Conclusion

These results suggest that polymorphisms in DUSP1 modulate plasma glucose and HDL‐cholesterol levels in obese patients potentially through alterations of gene methylation and expression. Funding: CIHR
Low‐fat milk protects against postprandial vascular endothelial dysfunction in adults with metabolic syndrome
Authors: Ballard Kevin D , Mah Eunice , Guo Yi , Pei Ruisong , Volek Jeff S , Bruno Richard S
Published: June 2021

Vascular endothelial dysfunction (VED) is common in metabolic syndrome (MetS), likely due to greater oxidative stress. We hypothesized that low‐fat milk would protect against postprandial VED by limiting oxidative stress responses that decrease nitric oxide (NO) bioavailability. Adults with MetS (n = 19, 28±2 y) completed a randomized cross‐over study that examined the ingestion of low‐fat milk (475 mL) or an isocaloric volume of rice milk on brachial artery flow‐mediated dilation (FMD), plasma glucose, malondialdehyde (MDA), arginine (ARG), and asymmetric dimethylarginine (ADMA) during a 3 h postprandial period. Postprandial FMD was unaffected by low‐fat milk, but decreased at 30–60 min (P<0.01) following rice milk. Glucose and MDA increased to a greater extent (P<0.001) in the rice milk trial, and MDA AUC0–3 h was related (P<0.01) to glucose AUC0–3 h (r = 0.75), and inversely related to FMD AUC0–3 h (r = −0.59). Plasma ARG decreased in the rice milk trial and increased in the low‐fat milk trial whereas ADMA/ARG increased by only rice milk. ADMA/ARG AUC0–3 h was related (P<0.05) to MDA AUC0–3 h (r = 0.55), and inversely related to FMD AUC0–3 h (r = −0.52). These findings suggest that low‐fat milk is an effective dietary strategy to protect against postprandial VED in MetS individuals by preventing hyperglycemia‐mediated lipid peroxidation that decreases NO bioavailability. Supported by Dairy Research Initiative.
Sugar‐sweetened Soda Intake and Obesity among Korean adults: the Korea National Health and Nutrition Examination Survey (KNHANES) 2007–2009
Authors: Lee Hye‐Seung Heather , Lee Hae‐Jeung , Stampfer Meir J. , Willett Walter C. , Lee Yoonna , Kim Choil , Cho Eunyoung
Published: June 2021

Background

We examined the association of sugar‐sweetened soda intake with overall (BMI) and abdominal adiposity (waist circumference) in Korea.

Methods

A national sample of 11,201 Koreans aged 19–64 was examined with cross‐sectional surveys (KNHANES) in 2007–2009. We conducted logistic regression analyses.

Results

We documented 3,477 cases of overall obesity (BMI =25kg/m2, 31%) and 3,899 cases of abdominal obesity (34.8%). Multivariate prevalence ORs of soda intake (never, =1 time/mo, 2–3 times/mo, 1 time/wk, >;1 time/wk) with overall obesity were 1.00 (ref), 1.02(95% CI 0.92–1.14), 1.06 (95% CI 0.91–1.22), 1.12 (95% CI 0.97–1.29), and 1.41 (95% CI 1.22–1.62, p for trend <0.0001). Soda intake was also positively associated with abdominal obesity (multivariate‐adjusted ORs for the same categories of soda intake: 1.00 (ref), 1.05 (95% CI 0.94–1.16), 1.11 (95% CI 0.95–1.28), 1.30 (95% CI 1.12–1.50), and 1.46 (95% CI 1.27–1.69, p for trend <0.0001). The associations were stronger among women than men. In addition, the positive association between soda intake and abdominal obesity was limited to those under 50 years old.

Conclusions

Soda intake was positively associated with both overall and abdominal adiposity in this population. Policy makers should recommend reducing the intake of sugar‐sweetened beverage such as soda for adults as well as children.
Strategies to Improve the Dietary Quality of Supplemental Nutrition Assistance Program (SNAP) Beneficiaries: An Assessment of Stakeholder Opinions
Authors: Leung Cindy W , Hoffnagle Elena E , Blumenthal Susan J , Lofink Hayley , Jensen Helen H , Foerster Susan B , Cheung Lilian W.Y. , Nestle Marion , Willett Walter C
Published: June 2021

This study examined the opinions of 522 individuals with stakeholder interest in the Supplemental Nutrition Assistance Program (SNAP) on strategies to improve dietary quality of SNAP participants. The top three barriers to improving dietary quality were: 1) unhealthy foods marketed in low‐income communities; 2) the high cost of healthy foods; and 3) lifestyle challenges faced by low‐income individuals. Most respondents (70%) also disagreed that current SNAP benefit levels were adequate to maintain a healthy diet. Stakeholders believed that vouchers, coupons, or monetary incentives for purchasing healthful foods might have the greatest potential for improving the diets of SNAP participants. Many respondents (78%) agreed that sugar‐sweetened beverages should not be eligible for purchases with SNAP benefits. More than half of all respondents (55%) believed retailers could easily implement such restrictions. A majority of respondents (58%) agreed that stores should stock a minimum quantity of healthful foods in order to be certified as a SNAP retailer, and most respondents (83%) believed that the USDA should collect data on the foods purchased with SNAP benefits. Results suggest that there is broad stakeholder support for policies that align SNAP purchase eligibility with national public health goals: reducing food insecurity, improving nutrition and preventing obesity
Household Food Insecurity and Obesity Risk in an Urban Slum in Brazil
Authors: Peterson Krysta , de Sousa Ribeiro Guilherme , dos Reis Mitermayer Galvão , Paploski Igor A.D. , Ko Albert , Salles‐Costa Rosana , Pérez‐Escamilla Rafael
Published: June 2021

Chronic diseases are growing among the poor. Household food insecurity (HFI) may partly explain this trend as individuals experiencing it may cope by consuming low‐cost high‐calorie meals with little nutritive value. This study aims to evaluate the prevalence of HFI and assess its relationships with obesity, health status and dietary intake among participants recruited in an urban slum in Salvador, Brazil. Risk for overweight and abdominal obesity was defined per WHO guidelines. HFI was evaluated using the Brazilian Food Insecurity Scale (EBIA). A total of 147 heads‐of‐households, defined as those responsible for household food preparation (39.8 ± 10.3 years) were interviewed to assess HFI, self‐reported health and diet, and anthropometry. HFI affected 82.3% of the sample (95% CI: 76.1–88.6%), with 20.4% experiencing severe HFI. A total of 69.3% of the population was either overweight or obese, abdominal obesity affecting 66.4%. Abdominal obesity was significantly associated with severe HFI (p=0.012) and BMI ≥ 25 was marginally associated with moderate (p=0.094) and severe HFI (p=0.069). Moderate/severe HFI was associated with lower fruit intake (p=0.022). Findings suggest that moderate and severe HFI is a risk factor for being overweight/obese and for unhealthy dietary behaviors in this disadvantaged community.

This project was funded by the Wilbur G. Downs Fellowship.
Association of diet quality score with periodontal disease in postmenopausal women: Evidence from the Women's Health Initiative Observational Study (WHI‐OS)
Authors: Tinker Lesley , Millen Amy , Wactawski‐Wende Jean , Pettinger Mary , Sarto Gloria , Vitolins Mara , Wallace Robert , Freudenheim Jo , LaMonte Michael , Genco Robert
Published: June 2021

Periodontal disease (perio‐dz) affects 40% of adult US women; prevalence increases sharply with age. Risk factors include smoking, SES, diabetes, overweight/obesity, hormones. Diet also may influence perio‐dz. A National Health and Nutrition Examination Survey III analysis showed that a good compared to poor quality diet assessed by Healthy Eating Index 2005 (HEI), resulted in lower odds of perio‐dz in adults (OR 0.40; 95% CI 0.19,0.85). Here we examine the association of diet quality (HEI) and perio‐dz in 74,222 postmenopausal women ages 50–79 years at baseline during WHI‐enrollment from 1994–98. Logistic regression analysis of cross‐sectional data was used to assess the association of self‐reported diet (HEI computed from food frequency questionnaire) with perio‐dz (ever told by dentist). Higher diet quality (higher HEI score) was associated with lower odds of perio‐dz. Data were limited to cross‐sectional analysis and causal direction may not be inferred.

Diet Quality Score: Healthy Eating Index
OR1
(95% CI)
P trend

<51 Poor (reference)
1.00

0.001

51–80 Needs Improvement
0.88
(0.81, 0.95)

>;80 Good
0.84
(0.77, 0.92)

Adjusted for demographics (age, race/ethnicity, income, education), health behaviors (smoking, physical activity, BMI, waist circumference, sunlight exposure, hormone therapy use, dental visits), chronic diseases.

Source of research support: National Heart Lung and Blood Institute
Quantitative measures of forearm skin color and self‐reported sun exposure scores predict serum 25(OH)D concentrations in a young multi‐ethnic population living in South Florida, US.
Authors: Ajabshir Sahar , Exebio Joel C , Zarini Gustavo G , Podesta Cinthia , Vaccaro Joan A , Huffman Fatma G
Published: June 2021

Objective

The aim of this study was to investigate the association between serum 25(OH)D level and quantitative measures of skin color along with a self‐reported sun exposure score.

Methods

This cross‐sectional study assessed the serum 25(OH)D level among 75 multi‐ethnic adult males (n=39) and females (n=36), aged 18–36 years living in South Florida. The skin color was quantified by a SMARTPROBE400 scanner and 25(OH)D was measured by ELISA method. A sun exposure questionnaire was used to determine the average annual sun exposure score. A linear regression model adjusted for age, gender, race, body mass index, alcohol consumption, tobacco use and years living in US was run.

Results

Total sun exposure score and forearm skin color were predictors of serum 25(OH)D level (P=.004 and P=.004 respectively). This association held after controlling for covariates (B=.292, P=.027 for forearm and B=.385, P=.005 for total sun exposure score). The model explained 24.6% of the variation in 25(OH)D.

Conclusion

The outcome of this study suggested skin color measures and sun exposure scores can be used as an indirect non‐invasive tool to estimate serum 25(OH)D level.
Novel sorghum brans containing bioactive compounds alter colon microbiota in response to a DSS‐induced chronic inflammatory state
Authors: Ritchie Lauren E , Sturino Joseph M , Azcarate‐Peril M Andrea , Turner Nancy D
Published: June 2021

We have shown that sorghum brans influence colon injury during inflammation, and bacterial metabolites (e.g., butyrate), suggesting alterations to the microbiota. To determine if the microbiota was altered, rats (n=80) were fed diets containing 6% fiber from cellulose (C), or black (B, 3‐deoxyanthocyanins), sumac (S, condensed tannins), or high tannin black (HT, both) sorghum bran. Inflammation was induced in 40 rats with three exposures to 3% dextran sulfate sodium (DSS), and the microbiota was characterized post DSS by pyrosequencing. There was no difference in bacterial diversity post DSS#2, yet, there were lower Chao species richness in S and HT compared to C and B rats (p<0.05). Post DSS#3 there was an increase in diversity (13.6–25%) and Chao (39–62%) compared to post DSS#2. Post DSS#3, C and B DSS rats had a lower and S and HT DSS rats had a higher Chao compared to controls (p<0.05). Post DSS#3, the proportion in the Clostridiales order was reduced (56%–79%) relative to post DSS#2, and there were diet effects post DSS#2 and #3 for bacteria in the Bacteroidales (both p<0.0001) and Clostridiales orders (p<0.0001 and p=0.039). The data indicate the microbiota is affected by DSS and polyphenol‐rich sorghum brans, which influence species richness and diversity. Thus, these sorghum brans may protect against reduced microbial diversity and richness typically observed in chronic inflammation. Funded by USCP Roo31A‐09.

Grant Funding Source: USCP Roo31A‐09
Ellagic acid inhibits hyperplastic conversion of human adiposederived stem cells through histone deacetylase‐dependent mechanisms
Authors: Kang Inhae , Kim Da Mi , Gourninei Vishinu , Zhao Bo , Shay Neil , Gu Liwei , Chung* Soonkyu
Published: June 2021

We have previously reported that Muscadine grape polyphenols (MGP) reduced high fat diet‐mediated visceral obesity in vivo. However, underlying mechanisms by which MGP reverses visceral obesity is unknown. The aim of this study was to determine the novel inhibitory roles of MGP on hypertrophic (increase in size) or hyperplastic (new fat cell formation) obesity. Consistent with reduced fat mass, epididymal adipocyte size was significantly smaller in MGP group compared to the HF‐control, suggesting that MGP reduces hypertrophic obesity. We also investigated the effects of MGP on adipogenesis using human adipose‐derived stem cells (hASCs). After fractionating MGP into anthocyanin and non‐anthocyanin fractions, only the non‐anthocyanin fraction inhibited adipogenic conversion of hASCs in a dose‐dependent manner. Among the non‐anthocyanidin polyphenols, ellagic acid has been identified as the responsible polyphenol that exclusively represses the adipogenesis. Ellagic acid repressed adipogenesis by blocking the obligatory reduction of histone deacetylase (HDAC) activity for adipogenic gene transcription. Both TSA‐sensitive and ‐ insensitive HDAC activities were modified by ellagic acid with selective increases of HADAC 1, 2 and 4, but not HADC3. Collectively, these data suggest that ellagic acid attenuates hyperplastic conversion of hASCs via HDAC activity mediated‐epigenetic modification.

Grant Funding Source: Florida Department of Agriculture and Consumer Service, Viticulture Research Program
Science and Me: An interactive program between science student and adult communities
Authors: Alexander Hannah
Published: June 2021

We present a course called “Science Outreach: Public Understanding of Science,” which trains student to communicate science in lay language. Students from a wide range of disciplines generate a series of presentations – the “Science and Me” series – in which each student prepares a 40‐minute, lay‐language presentation about an everyday topic, depicting the role that basic scientific research plays in that issue.

Students refine their talks by presenting them to their classmates and receiving extensive in‐class critiques. They then take their presentations to adult audiences in the community, in independent living facilities, the public library, or the Alumni Center. Colorful tri‐fold brochures, depicting the main points of the talks, are given to the audience at the end of each talk, and have proven to be a very popular aspect of the program.

We have adapted this course for graduate students, for upper level undergraduates, or high school students. Our experience shows that there is an adult audience that appreciates the interaction with “young scientists,” learning about science in lay‐language, and being provoked to think about how much basic science has affected their lives. For the students, this has been a unique opportunity to learn to communicate science in simple language, to gauge first hand the public's perception of science, and to make a direct, positive impact on the lives of adult residents in our community.