bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acid sphingomyelinase, syntaxin 4 and nitric oxide: how regulation of exo‐endocytic pathways is implicated in tumor chemotherapy
Authors: Perrotta Cristiana , Assi Emma , Bizzozero Laura , Cazzato Denise , Clementi Emilio 
Published: June 2021

Acid sphingomyelinase (A‐SMase) plays an important role in apoptosis and its activation involves the exocytosis from intracellular compartments to the plasma membrane. One of the players in the apoptotic event is nitric oxide (NO) that inhibits apoptosis through the generation of cyclic GMP (cGMP) and the ensuing inhibition of A‐SMase. Here we demonstrate the mechanism of this regulation and the possible implications.We found that A‐SMase is localized in lysosomes and in early/recycling endosomes, where it co‐localizes with syntaxin 4 (synt 4), a SNARE protein. After receptor activation A‐SMase translocates to the cell surface through an exocytic event in which synt 4 is required. In addition, we demonstrated that translocation of A‐SMase is required for its activation because the silencing of synt 4 inhibited A‐SMase activation. Synt 4 is the target of NO that acts via generation of cGMP and activation of G‐kinase, inducing phosphorylation of synt 4 on serine 78 and triggering proteasome‐dependent degradation of synt 4. Of importance, we found that this is a relevant mechanism in chemoresistance since NO produced by tumor‐associated macrophages protects glioma cells from cisplatin‐induced apoptosis. The identification of the interaction among ASMase, synt 4 and NO reveals an important mechanism of action of NO relevant in cancer and indicates synt‐4 as a novel target for antitumour strategies.
Does Digital Photography Improve the Accuracy of Diet Records in the Elderly?
Authors: Brown Alisa , Hakkak Reza , Gonzales Dana , Wolfe Robert , Hays Nicholas 
Published: June 2021

Utilizing digital photography alongside food records could prove to be a feasible way to refine the accuracy of food records in the elderly population. We determined whether the accuracy of 3‐day food records is improved by use of an accompanying digital photographic food record. Three day diet records were entered into the Nutrition Data System for Research (NDSR) both with and without the accompanying digital photography. We used total estimated energy expenditure (TEE), as assessed by the DRI's to determine overall accuracy of each method. Bland Altman regression, paired t‐tests and ratio of energy intake to total energy expenditure was used to determine variance between the methodologies. Our results shows that the digital photographic record helped to refine 157 items during data entry. Overall energy intake to TEE ratio was similar, indicating a high level of agreement between each method. Mean energy and protein intake did not significantly differ between the methodologies (p=0.75 and 0.73). We concluded that while accuracy was improved through the use of accompanying digital photographs, this did not significantly correct the tendency of underreporting. Given the qualitative improvement in food record data obtained using this technique, further research is needed to determine optimal use of digital photography.Supported by Dept. Dietetics and Nutrition and NIH to RW.
Association of body fat indicators with lipid concentrations in US children aged 6–11
Authors: Masters Melissa , Stanek-Krogstrand Kaye , Albrecht Julie A 
Published: June 2021

Childhood obesity is a major health issue in the US. The associations of body fat indicators were compared with lipid concentrations in a representative sample of US children.Data from 1819 participants aged 6–11 y from the 2001–2004 NHANES were assigned to specific groups according to gender (male/female) and BMI (normal/overweight/obese) and total cholesterol and HDL cholesterol were compared. Prevalences of adverse total cholesterol (>200 g/dL) and HDL cholesterol (<35mg/dL) in this population were determined according to BMI categories. Associations between three indicators of body fat (BMI, subscapular skinfold, triceps skinfold) and lipid concentrations were assessed.For children 6–11 y, 8.6% ± 0.9% had high total cholesterol and 5.0 ± 0.9% had low HDL cholesterol. Prevalence of adverse total and HDL cholesterol in obese US children was greater than normal weight participants. In multiple linear regressions adjusted for age, gender, survey period, and race‐ethnicity, HDL cholesterol levels were significantly inversely associated with BMI (p<0.001), subscapular skinfold (p<0.001), and triceps skinfold (p<0.001). Total cholesterol levels were significantly associated with subscapular skinfold (p=0.03) and triceps skinfold (p=0.007).High adiposity and adverse lipid concentrations were significantly associated in children aged 6–11 y.Grant Funding Source: NA
Examining the Anti‐inflammatory Properties of Blueberry Polyphenols Using MC3T3‐E1 Cells
Authors: Elam Marcus L , Zhang Jiyao , Feresin Rafaela , Hooshmand Shirin , Arjmandi Bahram H 
Published: June 2021

The objective of this study was to investigate the mechanisms by which total blueberry polyphenol extract (BPE) exerts its anti‐inflammatory function on MC3T3‐E1 preosteoblasts under inflammatory conditions. Cells were treated with BPE at concentrations of 0, 10, 100 μg/ml. After 24 h incubation, cells were stimulated with TNF‐α (10 ng/ml) and IL‐1 (10 ng/ml) individually or in combination for 24 and 48 hrs. Cells and supernatants were collected to assess NO production and for RNA extraction. Select gene expressions involved in bone cell differentiation were assessed using commercial cDNA array plates. BPE was able to suppress the increased NO production induced by either TNF‐α or IL‐1, suggesting the prevention of impaired osteoblastic differentiation. However, BPE had no significant effect on NO production when TNF‐α and IL‐1 were both present. At the molecular level, BPE upregulated RANKL and IL‐6 via the NF‐κB signaling pathway. In spite of this, BPE tended to increase gene expression of Runx2 and osterix, albeit not significantly. From these preliminary findings it can be suggested that BPE does not suppress bone turnover through osteoblast‐mediated activity unlike in vivo findings.Grant Funding Source : Margaret A. Sittion Professorship
Lipid extracts from edible blue‐green algae reduce the production of pro‐inflammatory cytokines by inhibiting nuclear translocation of NF‐κB in RAW 264.7 macrophages
Authors: Ku Chai Siah , Lee Jiyoung 
Published: June 2021

Chronic inflammation contributes to the pathogenesis of several metabolic diseases including atherosclerosis. We investigated anti‐inflammatory effects of lipid extract from edible blue‐green algae (BGA) such as Nostoc commune var. Sphaeroides Kützing (NO) and Spirulina Platensis (SP) in RAW 264.7 macrophages. The algal lipids were extracted into chloroform/methanol (2:1). Cells were pre‐treated with 100 μg/ml of the lipid extract for 12 hr and subsequently activated by 100 ng/ml lipopolysaccharide for 18 hr. Quantitative realtime PCR analysis showed that mRNA levels of pro‐inflammatory cytokines such as tumor necrosis factor α, interleukin 1β, and interleukin 6 are significantly repressed by NO and SP lipid extract. Cytokine array demonstrated that the secretion of pro‐inflammatory cytokines was also markedly reduced by both NO and SP lipid extract. The repressive effect was at least partly due to the inhibition of nuclear translocation of NF‐ κB. In addition, the repression of pro‐inflammatory cytokine expression by algal extracts was more potent than SN50, an inhibitor of NF‐κB nuclear translocation, suggesting that additional pathways may exist for the anti‐inflammatory effect of NO and SP lipid extract. In conclusion, BGA lipid extract contains anti‐inflammatory compounds that could be developed as a nutraceutical agent against inflammation‐related diseases.Grant Funding Source: NIH R21AT005152
Prevalence of dyslipidemia and cardiovascular disease (CVD) risk factors among young Mexican college students
Authors: Vazquez-Vidal Itzel , Andrade Flavia C.D , Teran-Garcia Margarita , Aradillas-Garcia Celia , Vargas-Morales Juan Manuel 
Published: June 2021

Our objective was to evaluate the prevalence of dyslipidemias and CVD risk factors among young Mexican college applicants. Fasting lipid profile (triglycerides (TG), total cholesterol (TC), HDL and calculated LDL) from 794 individuals 18–25 year‐old (56% females, BMI: 24.3±4.1 kg/m2) who applied to the UASLP in 2009. Only 41% of the population had a normal lipid profile. Fifty percent of the population had high‐LDL and 44% had low‐HDL. The most common lipid disorders were: low‐HDL (30%), high‐TC (9%), combined high‐TG and low‐HDL (7%) and combined high‐TC, high‐TG and low‐HDL (4%). Men had higher atherogenic profile ratios than women (all p<0.001): TC/HDL (41% vs. 31%), LDL/HDL (45% vs. 37%), and TG/HDL (55% vs. 41%). Low‐HDL and high‐LDL were the most common lipid disorders. These results suggest that young Mexican adults might be at risk for coronary heart events later in life. Sponsor by C09‐PIFI‐030606 (UASLP) and the University of Illinois Vice‐chancellor of Research, CHAD and USDA/NIFA Hatch Projects (#600108‐793000‐793323 and #600109‐698000‐698354).Grant Funding Source: USDA/NIFA Hatch Projects
Enteric Microbiome (EMB) of Breastfed Infants (BFI) on Complementary Feeding (CF) Regimens with Different Iron (Fe) Exposure
Authors: Krebs Nancy F , Sherlock Laurie , Robertson Charles E , Westcott Jamie , Culbertson Diana , Feazel Leah , Frank Daniel 
Published: June 2021

BackgroundThe low bioavailability of electrolytic Fe in infant cereals results in high Fe exposure for gut organisms, which may alter the balance of microbiota in the developing intestine.ObjectiveCompare the development and composition of the EMB among groups of healthy BFI on CF regimens that provided a range of Fe intake and excretion.MethodsHealthy BFI were randomized at 5 mo to Fe‐fortified infant cereal (IFC, n=4), Fe+Zn‐fortified cereal (IZFC, n=6), or meat (M, n=4). All infants continued breastfeeding and received no formula. Stool samples were obtained monthly from 5–9 months. Bacterial profiles were analyzed by broad‐range PCR of 16S rRNA genes and phylogenetic sequence analysis.ResultsAt 9 mo, mean Fe intake was 13 vs 3.7 mg/d for IFC+IZFC vs M, respectively. Sequence data identified significant differences in longitudinal development of the EMB by feeding group, including greater abundances of Clostridium Group XIVa (M > IFC & IZFC) and Bacteroidetes (IFC > IZFC & M). The M group also had higher species diversity.ConclusionsThis longitudinal study indicates that the composition of CF, including Fe exposure, influences the development of the infant enteric microbiota.Supported by NIH K24DK083772, T32 DK007658‐20S, 1R21HG00596, M01‐RR00069; The Beef Checkoff, NCBA
Human adipose‐derived stem cells attenuate cigarette smoke induced bone marrow hypoplasia via secretion of anti‐inflammatory cytokine TSG‐6
Authors: Xie Jie , Schweitzer Kelly , Johnstone Brian , Cook Todd , Feng Dongni , Albrecht Marjorie , Gao Yong , Justice Matthew , Cooper Scott , Broxmeyer Hal , Petrache Irina , March Keith 
Published: June 2021

IntroductionWe have previously observed bone marrow hypoplasia in a murine model of chronic smoking, which was ameliorated by murine adipose‐derived stromal cells (ASC). This study was designed to test the hypothesis that ASC exert their marrow protective effects through key paracrine factors.MethodsMice (NSG) were exposed to cigarette smoke (CS) for 1 day to 6 months. Human ASC or ASC conditioned media were administered through intravenous (i.v.) or intraperitoneal (i.p.) injections. Expression of TSG‐6 in ASC were knocked down by siRNA and confirmed by real‐time PCR and ELISA. BM hematopoietic progenitor subsets were quantified by colony forming‐unit assays. Possible engrafted human ASC in mouse BM were examined by anti‐human nuclei staining.ResultsCS (6 mos) significantly reduced BM hematopoietic progenitors (vs. nonsmoker, 50.7%, p<0.01), which was restored by human ASC i.p. (110.6%, p>0.05) and i.v. (70.9%; p>0.05). Such damage occurred acutely after one‐day exposure (61.6 %, p<0.01), and could be ameliorated with either ASC (111.0%, p>0.05) or ASC conditioned media (105.7%, p>0.05). Knocking down TSG‐6 (>90%) abolished the protective effect of ASC. No human cells were detected in recipient mouse bone marrow.ConclusionsThe protective effects of ASC against smoking‐induced myelosuppression are mediated by paracrine factor TSG‐6 rather than cell engraftment or differentiation.Research supported by American Heart Association
Fluorescence imaging reveals differences in mitochondrial function along the collecting duct
Authors: Courtneidge Holly Robyn , Crawford Carol , Hall Andrew M , Peppiatt-Wildman Claire M 
Published: June 2021

The collecting duct (CD) consists of two different cell populations, principal cells (PCs) and intercalated cells (ICs), which have distinct solute transport functions. Transport and metabolism are closely coupled in the nephron, thus we hypothesised that intrinsic differences in PCs and ICs mitochondrial function might exist. Mitochondrial function can be measured in intact rat kidney slices using confocal and multiphoton microscopy (1,2); here we apply this approach to investigate our hypothesis.PCs and ICs have distinct morphological differences, which enabled their identification during live imaging. Heterogeneity was observed in mitochondrial signals along the CD. Mitochondrial membrane potential, measured using tetramethylrodamine methyl ester (TMRM), was higher in PCs (34.45±3.08) than ICs (16.82±8.23) (n=3, p=0.009), and this signal was not altered by dye efflux inhibitors. Fluorescence signals from the endogenous fluorophores NADH and FAD+ (substrates for complexes I and II in the respiratory chain, respectively) were higher in ICs than in PCs (p=0.03 and p=0.056 respectively).In summary, fluorescence imaging reveals intrinsic differences in mitochondrial function between PCs and ICs, which may be important in understanding (patho)physiology of the CD.Research supported by the Medical Research Council
Peptide expression and purification to elucidate the mechanism of vascular α‐2C adrenoceptor translocation
Authors: Fidelibus Robert , Jeyaraj Selvi C , Unger Nicholas T , Biesiadecki Brandon J , Chotani Maqsood A 
Published: June 2021

In response to physiological cold temperatures cutaneous blood vessels constrict to reduce heat loss. This constriction is mediated by smooth muscle G protein‐coupled α2C‐adrenoceptors (α2C‐ARs) which translocate from the transGolgi to the plasma membrane upon cooling. We hypothesize that this translocation is due to protein‐protein interaction between α2C‐AR C‐terminus and the protein filamin‐2. The goal of this study is to test this mechanism of receptor translocation experimentally by decoy peptide interference. We predict that interfering with this interaction will inhibit translocation of α2C‐ARs and subsequently receptor function.The DNA sequence encoding 11 amino acids of the cell‐permeable HIV transactivator of transduction (TAT) domain was fused in frame with the α2C‐AR C‐terminus to generate the p‐TAT‐α2C‐AR‐ C‐terminus bacterial expression vector. BL21‐CodonPlus competent cells were used to optimize peptide expression at 30°C. The parameters tested were bacterial growth, presence of antibiotics, induction time, cell lysis buffers, sonication and salt precipitation conditions. Peptide expression was confirmed by Western blot and Coomassie techniques. The peptide will be purified by ion‐exchange chromatography, fluorescently labeled for tracking and delivered to human cutaneous smooth muscle cells to assess cellular activity for endogenous α2C‐ARs.
Structural Biology of Methylation‐mediated Epigenetic Regulation
Authors: Patel Dinshaw J. 
Published: June 2021

The lecture will present our research on recognition events controlling epigenetic regulation mediated by methylation marks on histone tails and at CpG sites on DNA.Specific topics will include recognition of methyllyisne marks by reader elements in ADDATRX (Haitao Li), TRIM24/33 (Zhanxin Wang) and MLL1 (Zhanxin Wang and Jikui Song), erasure of lysine methylation marks by the KMD2A jumonji family lysine demethylases (Zhongjun Cheng), and DNMT1‐mediated active and autoinhibitory mechanisms of maintenance DNA methylation (Jikui Song).Collaborators: Yang Shi (Harvard) and Haitao Li (Tsinghua) on ADDATRX, C. David Allis (Rockefeller) on MLL1, Michelle Barton (M. D. Anderson) on TRIM24, Joan Massague (Sloan‐Kettering) on TRIM33, and Or Gozani (UCSF) on KMD2A.
Electrospun Proteoglycan Matrices for Tracheal Tissue Engineering
Authors: Hinderer Svenja , Bayrak Alexandra , Schesny Marianne , Hampel Martina , Seifert Martina , Schenke-Layland Katja 
Published: June 2021

Decorin (DCN) is a proteoglycan (PG) present in the extracellular matrix (ECM) of many tissues, including the trachea. Electrospinning is a suitable method for three‐dimensional (3D) scaffold fabrication to mimic the ECM's fibrous structure. In this study, we generated electrospun DCN‐polymer hybrids to obtain scaffolds that allow human tracheal cell (hTC) seeding.MethodsDCN containing scaffolds were fabricated and characterized using scanning electron microscopy, contact angle measurements and dynamic mechanical analyses. Immunofluorescence (IF) staining was performed to detect DCN within the scaffold. For cell‐matrix interaction studies, we seeded primary hTCs and confirmed their phenotype by using immunocytochemistry.ResultsAnalyses of the 3D substrates revealed a fibrous scaffold with a random fiber orientation. An average fiber diameter of 0.42 ± 0.20 μm and a pore size of 14.4 ± 6.4 μm2 was determined. Antibody staining for DCN showed the PG randomly distributed throughout the entire scaffold. After cell seeding, IF staining with an antibody against FOXJ1 revealed that ciliated hTCs adhered and proliferated on the scaffolds.ConclusionHere, we showed the successful electrospinning of PGs in combination with polymers to generate a fibrous scaffold with features of the natural ECM. Our data suggest that these substrates are excellent for applications in regenerative medicine.Grant Funding Source: Fraunhofer‐Gesellschaft (Attract 692263 to K.S.‐L)
Caffeic Acid Phenethyl Ester protects burn wounds against oxidative stress and improves wound healing
Authors: Monte-Alto-Costa Andrea , Santos Jeanine Salles 
Published: June 2021

Caffeic acid phenethyl ester (CAPE) is an active component of propolis, and has been shown to have anti‐inflammatory and antioxidant effects; in this study we studied its effects on burn wound healing. Twenty one female Wistar rats were divided in three groups: control (no burn)+CAPE, burn and burn+CAPE. A third‐degree burn was created. The CAPE treatment (10 μmol kg‐1; i.p.) began immediately after burn and lasted until euthanasia (14 days after burn). Fourteen days after wounding the burn+CAPE group presented greater wound contraction when compared to burn group. In plasma, lipid peroxidation was higher in burn group compared to control and burn+CAPE group. In wounds, burn+CAPE group presented a smaller lipid peroxidation than burn group. Carbonyl levels in plasma and lesions of the burn group were increased when compared to control group. In burn+CAPE group carbonyls levels were greater than the control only in wounds. Catalase activity was also analysed, and burn+CAPE group presented greater activity when compared to burn, but without difference when compared to the control group. It was also observed that both burn and burn+CAPE groups present a higher myeloperoxidase activity than control group, but the burn+CAPE group presented smaller myeloperoxidase activity compared to burn group. CAPE treatment improved wound contraction and reduced the oxidative damage of burns.Support: CAPES
Elucidation of mechanisms of biochemical regulation of fumarase activity under physiological conditions
Authors: Mescam Muriel , Vinnakota Kalyan C , Beard Daniel A 
Published: June 2021

The enzyme fumarase catalyses the reversible mechanism of hydration/dehydration of fumarate to malate. This reaction is a critical step of the tricarboxylic acid (TCA) cycle and hence of the synthesis of ATP in metabolism. In a recent study, we have identified a catalytic mechanism for the enzyme in various conditions of buffer concentrations, pH and initial substrate concentrations [1]. In the current study, we investigate the influence on the kinetics of fumarase, of various anions such as phosphate, citrate, isocitrate, ATP and ADP. An eleven‐state computational model is fitted to time‐courses of fumarate hydration, obtained under physiological conditions in terms of ionic strength, pH, temperature and concentrations, in order to determine the potential inhibitory/activating effect of each anion on the kinetics of fumarase. This combination of experiments and computational modeling provides a quantitative understanding of the enzyme's catalytic mechanism.This work is supported by the NIH Grant HL094317.
Decline in adipogenesis contributes to peripheral subcutaneous fat loss in older humans
Authors: Caso Giuseppe , McNurlan Margaret A , Mileva Izolda , Stein Seth , Gelato Marie C 
Published: June 2021

Aging is associated with redistribution of body fat characterized by a relative loss of subcutaneous limb fat and accumulation in trunk and visceral areas. The loss of subcutaneous peripheral fat is associated with metabolic abnormalities, particularly insulin resistance. The causes and mechanisms of loss of peripheral fat with aging are not completely clear.The aim of this study was to assess whether defects in adipogenesis contribute to fat loss in aging humans, as suggested from animal studies.Preadipocytes isolated from subcutaneous peripheral fat of healthy young and elderly subjects were compared in their ability to replicate and differentiate.The results show that both the rate of replication of subcutaneous peripheral preadipocytes and their ability to differentiate are impaired with aging. The reduction in adipogenesis is accompanied by a higher plasma level of the inflammatory marker, soluble tumor necrosis factor receptor 2, and greater release of tumor necrosis factor α from fat tissue. Thus, the gradual loss of peripheral fat in aging humans may in part result from a defect in adipogenesis, which may be linked to inflammation and/or to increased release of proinflammatory cytokines from fat tissue.(Supported by NIH grants DK049316 and 5‐MO1‐RR‐10710; and New York Empire Clinical Research Investigator Program (ECRIP) fellowships to GC and SS)
Mg supplementation acutely affects intracellular Mg2+ in human leukocytes
Authors: Nestler Axel , Vormann Juergen , Kolisek Martin 
Published: June 2021

Intracellular Mg2+ ([Mg2+]i) is overall well regulated, however it is not known whether Mg supplementation may lead to its acute changes. Therefore we examined acute effect of Mg administered either in form of MgO or Mg citrate on total plasma Mg ([Mg]p) and [Mg2+]i in human leukocytes.Study design51 healthy individuals were randomized into 3 groups. One group received 300 mg Mg as MgO (n = 20), another group received 300 mg Mg as Mg‐citrate (n = 21). A control group contained 10 persons. Samples were obtained at 0 h and 1, 3, 9, and 24 h after supplementation. Probands ingested the supplement after breakfast. All probands received identical food and table water containing low‐Mg during the sampling time. [Mg]p was determined by AAS. [Mg2+]i was assessed as 340/380 nm mag‐fura 2 ratios in leukocytes of the probands.ResultsSignificant changes in [Mg]p could not be observed between groups. However supplementation with Mg lead to a significant increase of 340/380 nm ratios after 3, 9, and 24 h. After 9 and 24 h, the 340/380 nm ratios were significantly higher for Mg‐citrate than for MgO.ConclusionEven though only minor changes in [Mg]p could be detected already 3 h after Mg supplementation [Mg2+]i increased but returned to near normal after 24 h. Mg given as Mg‐citrate induced significantly higher increases of [Mg2+]i as if given as MgO.