bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotype switching by inflammation‐inducing polarized Th17 cells, but not by Th1 cells
Authors: Shi Guangpu , Cox Catherine A. , Vistica Barbara P. , Wawrousek Eric F. , Gery Igal 
Published: June 2021

Analyses of inflammation inducing Th cells revealed that a portion of these cells express both IFN‐γ and IL‐17, suggesting that Th1 and/or Th17 may switch their phenotype. Here, we examined phenotype retention in a system in which polarized Th1 or Th17 cells specific against hen egg lysozyme (HEL) induce ocular inflammation in recipient mice expressing HEL in their eyes. Whereas no switching to Th17 was detected in Th1 recipient eyes, substantial proportions of transferred Th17 expressed IFN‐γ, or both IFN‐γ and IL‐17 in Th17 recipient eyes. The phenotype switch of Th17 cells increased with time and was attributed to exposure to IL‐12 that is expressed in the inflamed eyes. Incubation in vitro with Th1 polarizing cocktail (IL‐2+IL‐12) converted most Th17 into IFN‐γ or IFN‐γ/IL‐17 expressing cells, but no reciprocal conversion was noted with Th1 cells. Furthermore, whereas Th1 cells did not express ROR‐γt following incubation with Th17 polarizing cocktail, Th17 expressed T‐bet following incubation with Th1 cocktail. Thus, polarized Th1 cells fully retain their phenotype, while Th17 switch and express IFN‐γ or both IFN‐γ and IL‐17, as well as T‐bet, following exposure to IL‐12.This study is supported by NEI/NIH intramural program.
Downregulation of Cellular Energy Sensor during Disease condition results in Alteration of Lipid Homeostasis in Immune Cells
Authors: Giri Shailendra , Nath Narender , Khan Mushfiquidin , Singh Avtar K , Singh Inderjit 
Published: June 2021

AMP‐activated protein kinase (AMPK), an energy sensing metabolic switch of mammalian cells, was observed to be down regulated during T cells mediated autoimmune disease. A catalytic subunit of AMPK, alpha1, was predominantly expressed in T‐ and antigen presenting cells. During EAE disease, activity of AMPK was significantly downregulated in thymocytes, spleen cells and brain. Decreased AMPK activity results increased lipid biosynthesis and their content in total T cells, adherent and non‐adherent spleen cells at disease state. Increased lipids biosynthesis leads to the higher proliferative state of these cells was evident from active form of Akt, p42/44 and reduced levels of p21 and p27. AMPK activators restored lipid alteration in total spleen cells by reversing the AMPK activity and inhibited production of pro‐inflammatory cytokines under in vitro stimulation. All together, our results demonstrated that downregulation of AMPK‐mediated altered lipid metabolism in immune cells, resulted an inflammatory environment may be one of the critical aspects of pathogenesis during EAE or Multiple Sclerosis and identified AMPK as a novel therapeutic target for autoimmune diseases.Grants support: Mainly by RG 3810‐A‐1 and PP1283 from the MS Society (SG) and in part by (NS‐22576, NS‐34741, NS‐37766 and NS‐40810) from NIH (IS).
IgE accelerates in vitro development and modifies the phenotype of mast cells
Authors: Kashiwakura Jun‐ichi , Xiao Wenbin , Kitaura Jiro , Kawakami Yuko , Wilson Bridget S. , Blank Ulrich , Kawakami Toshiaki 
Published: June 2021

Monomeric IgEs possess a wide range of heterogeneity in their ability to induce mast cell activation in the absence of multivalent antigen. Highly cytokinergic (HC) IgEs induce a variety of mast cell activation events including cell survival, degranulation, cytokine production, and migration, whereas poorly cytokinergic (PC) IgEs do so inefficiently. Here we investigated the effect of monomeric IgE molecules on mast cell differentiation. When bone marrow cells are cultured with monomeric IgEs, cell number is increased compared to cultures without IgE. Furthermore, time in culture required to generate greater than 80% pure mast cells is decreased. IgEs can induce mast cell progenitors to differentiate into mast cells. mRNA expression levels of several mast cell proteases and mast cell‐related transcription factors such as Egr‐1, a transcription factor involved in the production of TNF‐α, are increased in mast cells cultured with an HC IgE compared to those cultured with a PC IgE or without IgE. Consistent with this, expression of TNF‐α is higher in mast cells cultured with an HC IgE. Taken together, these results suggest that monomeric IgEs, especially HC IgEs, not only promote mast cell development, but also modulate the mast cell phenotype.Funded in part by the NIH grant AI50209.
Anti‐tumor effect by dendritic cells stimulated with IL‐2 in OT‐1 model
Authors: YANG QIN , Herberman Ronald B. , Lotze Michael T. , Kalinski Pawel , Basse Per H. 
Published: June 2021

Background:Recently, IKDCs expressing both natural killer (NK) and dendritic cell (DC) characteristics have been described: these NK‐like DCs “convert” from cells with NK cell lytic activity and NK receptor expression, into cells acquiring MHC class II and the requisite molecules for APC function. In an attempt to stimulate IKDC‐like activity in bone‐marrow‐derived DCs (BMDCs), we stimulated the BMDCs with IL‐2. These “DCs‐IL‐2” cells possessed an impressive anti‐tumor effect in mice when injected s.c, mixed with M05 tumor cells.Methods:1) Vaccination with DCs‐IL‐2+MO5 in OT‐1 model; 2) Rechallenge of tumor‐free mice; 3) Flow and image analysis.Results:1) The DCs‐IL‐2‐treatment demonstrated an impressive anti‐tumor effect in that no tumor growth was seen in four of the five mice that received DCs‐IL‐2 + MO5 tumor cells on the right flank and M05 cells alone on the left flank; 2) Three out of the four tumor‐free mice did not grow tumors when re‐challenged with MO5 tumor cells. One mouse developed tumors, but much delayed compared to control mice; 3) Flow data demonstrated that 10–20% of the DCs‐IL‐2 acquired A‐NK phenotypic markers, while maintaining their DC phenotypes.Conclusion:The DCs‐IL‐2 have a promising potential to improve cancer immunotherapy and we will continue to study the phenotype, lineage commitment, and in vivo relevance of these cells.
Selective stimulation of mast cells with a TLR2 agonist inhibits tumor growth in vivo
Authors: Oldford Sharon Ann , Leiva Carlos A. , Johnston Brent , Marshall Jean S. 
Published: June 2021

Mast cells are potent effector cells abundant at the growing edge of solid tumors, where they can enhance angiogenesis. Mast cells stimulated with the Toll‐like receptor‐2 (TLR2) activator Pam3CSK4 lipopeptide (LP) secrete angiostatic chemokines. We hypothesized that LP‐stimulated mast cells would have anti‐tumor potential. LP‐activated bone marrow derived mast cellls (BMMC) significantly inhibited the growth of B16.F10 melanoma (n=10, P=0.0195) and LLC1 Lewis lung carcinoma (n=9, P=0.0078), in Matrigel plugs in vivo. The presence of BMMC alone had no significant effect on tumour growth. Tumors containing LP‐activated BMMC had reduced blood vessel frequency (B16.F10, n=7, P<0.05; LLC1, n=7, P=0.08) and blood volume (LLC1, n=6, P<0.05), correlating with tumor weight (r=0.48, P=0.02). In vitro studies demonstrated this anti‐tumor effect was not attributable to BMMC‐mediated tumor cytotoxicity. Dependence on mast cell expressed TLR2 was confirmed by the lack of LLC1 or B16.F10 tumor inhibition in C57Bl/6 mice using LP and BMMC derived from TLR2 knock‐out mice. Protein array analyses identified several candidate mediators that may contribute to the anti‐tumor effect of LP‐activated BMMC. These findings suggest a novel role for mast cells as intermediaries for anti‐cancer immunotherapiesSupported by National Cancer Institute of Canada. SAO is supported by the Cancer Research Training Program.
CD8 T cell response to IL‐15/IL‐15Rα complex is MHC class I dependent
Authors: Stoklasek Thomas A , Lefrancois Leo 
Published: June 2021

Recent findings illustrate that IL‐15 operates via a unique mechanism termed transpresentation. In this system, IL‐15 produced by one cell type is bound to IL‐15Rα expressed by the same cell and presented to apposing cells expressing the IL‐15Rβ/γC complex. We have recently shown that administering soluble IL‐15Rα complexed with IL‐15 can greatly enhance IL‐15 activity by increasing IL‐15 half‐life and forcing transpresentation of IL‐15. Furthermore, IL‐15/IL‐15Rα complex can cause the proliferation and maturation of naïve CD8 T cells. We now show that the CD8 T cell response to exogenous IL‐15/IL‐15Rα complex is MHC class I dependent. In the absence of MHC class I, naïve CD8 T cells scarcely proliferate in response to IL‐15/IL‐15Rα complex. In addition, providing specific peptide along with IL‐15/IL‐15Rα complex can enhance the proliferation of antigen‐specific CD8 T cells. The responding antigen‐specific CD8 T cells undergo an expansion and contraction phase, resulting in a larger frequency of remaining memory‐phenotype cells. These data suggest that IL‐15/IL‐15Rα complex has selective effects on antigen activated CD8 T cells. Our findings have important implications for directing IL‐15/IL‐15Rα complex based therapy to specific antigen targets, and illustrate the possible adjuvant uses of IL‐15/IL‐15Rα complex.NIH Grant AI‐051583 (to L.L.) and NCC Predoctoral Fellowship (to T.A.S.).
Regulation of CD8+ T cell‐associated Programmed Death‐1 (PD‐1) expression by antigen‐dependent and ‐independent signaling
Authors: Wong Raymond , Smith Kent , Tam Victor , Meisenberg Brenna , Quach Angeline , Carillo Mayra , Bot Adrian 
Published: June 2021

PD‐1/PD‐1 ligand interaction regulates immune homeostasis and is a potential barrier to optimal T cell activity against viruses and tumors. Using a lymph node‐targeted immunization approach, we evaluated the impact of antigen‐dependent and ‐independent signaling on the phenotype of CD8+ T cells, with focus on expression of the inhibitory receptor PD‐1. The levels of antigen exposure and co‐stimulation provided by CpG oligodeoxynucleotide (ODN) adjuvant, respectively, had striking and opposite effects on PD‐1 acquisition by epitope‐specific CD8+ T cells (∼5 to 65% positive). Elevated PD‐1 expression was associated with decreased functionality on a cell‐for‐cell basis, which was at least partly reversible by antibody‐mediated PD‐1 blockade. Low antigen exposure in context of an optimal immune co‐stimulatory signal – via peptide + CpG ODN or DNA plasmid immunization – yielded low PD‐1‐expressing central and peripheral memory cells with substantial proliferation and differentiation potential upon subsequent antigen stimulation. These findings shed light on the distinctive mechanism of action of DNA and peptide vaccines and, in general, the homeostasis of CD8+ T cells via induction of an inhibitor receptor.Funding for this research was provided by MannKind Corporation.
Relative animal versus plant foods consumption and risk of childhood obesity
Authors: Sabaté Joan , Lousuebsakul Vichuda 
Published: June 2021

Background. During the last decade, the prevalence of childhood obesity in the U.S. has doubled.Materials and Methods. The association between dietary intake and obesity was examined using a multivariate logistic regression model on 1,764 California school children, ages 7 to 18 years, who completed a 106 item food frequency questionnaire. The relative frequency of consumption of meat, poultry, fish, dairy products and eggs were combined and classified as animal product intake. Similarly, the relative frequencies of consuming cereal, legumes, nuts, fruits, vegetables and vegetable protein products were combined as plant foods intake. A child was classified as obese if his or her body mass index (weight/height2) was above the 75 percentile value of the age and gender‐specific population subgroup.Results. Compared to girls, boys had a 22% lower risk of obesity (OR=0.78, 95%CI: 0.62–0.99). Compared to the lowest animal products intake quartile (19% or less), the risk of obesity increased by 75%, 46% and 69% respectively as quartiles of animal product consumed increased. Children with a high proportion of plant foods in the diet had a 38% lower risk of obesity (OR= 0.62, 95%CI: 0.41–0.93) compared to those with low consumption.Conclusions. Among children, a high proportion of plant product consumption can prevent obesity where as a high proportion of animal products in the diet increases the risk of obesity.
Variability in results from predicted resting energy needs as compared to measured resting metabolic rate: Determining the most accurate formula for use in younger children
Authors: Kim Eun‐Kyung , Kim Jae‐Hee , Lawrence Jeannine Clunk 
Published: June 2021

Introduction: Energy prediction equations are often used to predict energy needs in young children, however little data is available regarding their accuracy in this population. This study compared measured resting energy expenditure to commonly‐used prediction equations to determine the most accurate formula.Methods: 42 kindergarten children (17 boys and 25 girls; mean age 5.0 ± 0.9 y.o.) from the Gangneung area, South Korea were included. Measurements included: resting metabolic rate (MRMR; TrueOne 2400 metabolic cart); weight and height (digital scale/stadiometer); body fat (bioelectrical impedance analysis, Inbody720). Prediction equations included: the Harris‐Benedict, Dietary Reference Intakes, Mifflin, Maffeis, Body surface area, WHO/NAO/FAO, Schofield (‐W and –HW), Owen, FAO/WHO/UNU, and Cunningham.Results: Mean MRMR was 878.1 ± 56.1 kcal/day (no significant gender differences). Only results from the Maffeis and Schofield equations were not significantly different from the MRMR. Others showed differences of up to 227 ± 61.4 kcal/day.Conclusions: Care should be taking when choosing an energy prediction equation for younger children to select one that is most accurate. In this group of 4–6 y.o.'s both the Maffeis and the Schofield equations would be appropriate for predicting energy needs.Research support: Kangnung National University, South Korea
Relationships of smoking and alcohol consumption on atherogenic index, antioxidant status and lymphocyte DNA damage in Korean men
Authors: Oh Hye Sun , Kim Hyun Young , Lee Hye‐Jin , Park Yoo Kyoung , Kang Myung‐Hee 
Published: June 2021

The purpose of this research was to investigate the influence of alcohol consumption and smoking habits on atherogenic index, antioxidant enzymes, level of lipid peroxidation and lymphocyte damage. The participants included 386 men 19–60 years of age. The level of lipid peroxidation was measured as the level of conjugated diene (CD) and the lymphocyte DNA damage was measured by COMET assay. In the observed sample population, we categorized the subjects into 15 groups. Subjects were divided into 5 groups: A0 (0 g/day, n=49), A1 (1–70 g/day, n=98), A2 (71–140 g/day, n=84), A3 (141–350 g/day, n=101), A4 (>350 g/day, n=40), and then were further divided into S0 (nonsmoker, n=92), S1 (1–15 cigarettes/day, n=138), S2 (>15 cigarettes/day, n=142) depending on the level of cigarette consumption. Regardless of the alcohol intake, there was a continuous increase of the atherogenic index with the increasing quantity of cigarette smoking. HDL‐C was increased with the increasing level of alcohol consumption. In addition, regardless of the alcohol intake, CD level was lowest in the S0 groups and highest in the S3 groups. Antioxidant status measured by plasma tocopherol, carotene and vitamin C level did not differ significantly among groups. The DNA damage (assessed by tail DNA) was greatest in the heavy smokers compared to the non‐ or light smokers. Our result showed that the exposure of cigarette smoking has higher impact on the level of antioxidants and DNA damage than the combined effect with alcohol consumption.This study was supported by a grant from Kyung Hee University Research Fund in 2004 (KHU‐20040945)
Relationships Among Omega‐3 fatty acids, Anthropometrics, and Biochemical Markers in College Students
Authors: Barber‐Heidal Kimberly , Broughton Kenneth Shane , Malinauskas Brenda M , Hickner Bob , Duffrin Melani 
Published: June 2021

Students participated in a college life survey, an n‐3 FFQ, and a fasting blood draw. Participants were classified as normal weight (BMI < 25 kg/m2, n=27.), overweight (25–29.9 kg/m2, n=16), or obese (≥30 kg/m2, n=12.). IL‐6 negatively correlated with plasma phospholipid EPA (−0.387) and DHA (−0.396) and positively with saturated fat (0.469) (P<0.05) only in the normal weight. While IL‐6 correlated with lipids in the normal weight, a positive correlation was found with IL‐6 and body weight (BW) in the obese (0.627) and overweight (0.506). Ghrelin had a negative correlation with BW (−0.504), EPA (−0.415) and total n3 (−0.397) and a positive correlation with the n6:n3 ratio (0.496) in the normal weight (P<0.01) while not correlating with any of these variables in the overweight and obese.Blood n‐3 PUFAs were similar in overweight and obese women, but were 25% higher in overweight than normal weight women. The difference in women total n‐3 PUFA levels was induced by cumulative differences in EPA, DHA, and DPA and the combined influence on total n‐3 PUFA as there was no difference within the sex for the specific n‐3 PUFA. There was no difference in total n‐3 PUFA in men; however, the overweight had significantly lower DHA than the normal and obese men at a mean of 3.0 mol% vs. 4.9 and 4.6 mol%, respectively. While there were differences between individuals with different BMI's the health implication need to be evaluated.
Effects of vitamin E on serum cytokine levels in healthy adults
Authors: Sundaresan Sinju , Malone Brenda , Radcliffe John , Imrhan Victorine 
Published: June 2021

Effects of Vitamin E on serum cytokine levels in healthy adultsPurpose: The study determined the effects of increased dietary intake of Vitamin E (~15g per day) on serum levels of vascular endothelial growth factor (VEGF), interleukins (IL)‐1α, 1β, IL 2, IL 4, IL 6, and tumor necrosis factor (TNF‐α) in healthy adults. Methods: Healthy volunteers were randomly assigned to Control (C) and Intervention (I) groups (n=15) and allowed to consume normal diets for one week. Group C continued their normal diets for 4 weeks and group I was given vitamin E‐rich foods (muffins with cottonseed oil, almonds, broccoli, wheat germ) for 4 weeks. Weekly 3‐day diet diaries were analyzed for nutrients and energy using NDSR program. Blood samples were assayed for VEGF, interleukins and TNF‐α at baseline and week 5. Results: At the end of week 5, Group I had 2.5‐fold higher IL‐α, and 2.2‐fold higher IL‐1β production than Group C (P<0.05) respectively. This group also had 2.0‐fold higher IL‐2, IL‐4, and 1.8‐fold higher TNF‐α production than Group C (P<0.05) respectively. However, IL‐6 production was not significantly enhanced in Group I at the end of week 5. VEGF levels in Group I was 0.8‐fold lower (NS; P=0.059) than Group C at the end of week 5. Conclusion: Serum pro‐inflammatory IL 1‐α, 1‐β, IL 2, IL 4, and TNF‐α levels were significantly improved by including vitamin E‐rich foods in the diet without affecting energy intake, with no changes in IL‐6 and VEGF levels in these healthy adults.
Modular architecture and human disease alleles of the mitochondrial replicative DNA helicase
Authors: Kaguni Laurie S. , Ziebarth Tawn D. , Matsushima Yuichi , Farr Carol L. 
Published: June 2021

The human mtDNA helicase shares amino acid sequence and functional similarities with bacteriophage T7 primase‐helicase. mtDNA helicase exists as a hexamer that is destabilized under low salt conditions, but can be maintained by inclusion of Mg2+ and ATP, and by temperatures above 20 °C. Limited proteolysis reveals distinct N‐ and C‐terminal polypeptides that represent minimal structural domains, and yields several stable fragments that differ in the presence of nucleoside di‐ and triphosphate and DNA. Truncations of the N‐ and C‐termini affect differentially DNA‐dependent ATPase activity, and whereas a C‐terminal domain polypeptide is functional, an N‐terminal domain polypeptide lacks ATPase activity.Molecular analysis of the Drosophila homolog was used to evaluate the physiological consequences of active site and human disease alleles. RNA interference reduces expression of d‐mtDNA helicase to an undetectable level in Schneider cells, causing an ∼5‐fold decrease in mtDNA copy number, whereas overexpression increases mtDNA levels 1.4 fold. Overexpression of helicase active site mutants results in a severe depletion of mtDNA, and a dominant‐negative lethal phenotype. Interestingly, overexpression of mutants analogous to human disease alleles show differential effects, ranging from dominant negative effects to increases in mtDNA copy number. This research was supported by NIH grant GM45295.
The characterization of the morphology and intrinsic oscillatory contractions in pudendal arteries of aging normotensive rats
Authors: Hannan Johanna , Blaser Mark , Pang Judy , Bennett Brian , Pang Stephen , Adams Michael 
Published: June 2021

Aging increases the risk of erectile dysfunction (ED) and cardiovascular diseases. We examined the effects of age on erectile function and vascular structure and function, particularly with respect to intrinsic oscillatory properties (vasomotion) of the primary penile resistance artery (pudendal).Methods: Erectile responses were assessed in 15 and 50 week Sprague‐Dawley rats. After sacrifice, myograph‐mounted pudendal arteries were pre‐contracted and responses to acetylcholine and L‐NAME assessed. Oscillations were analysed via FFT and the signals separated by power density spectra; very low (VLF) 0.002‐0.05 Hz, low (LF) 0.05‐0.2 Hz, high (HF) >0.2 Hz.Results: Aged rats had severe ED that corresponded with a disproportionately thickened wall of the pudendal (~2‐fold). In both young and old rats, pudendal vasomotion was dominated by VLF oscillations, whereas aortic waves were mainly LF and HF. Aging increased VLF activity in the pudendal (4‐fold), but not aorta. L‐NAME abolished aortic VLF activity, but did not alter pudendal oscillations.Conclusion: The preponderance of VLF oscillations in the pudendal arteries suggests there is a novel regulation for controlling penile inflow that is independent of nitric oxide. The aging associated morphological and vasomotion changes in the pudendal suggests a causative role for pathogenic vascular remodelling of pre‐penile vessels in aging‐induced ED.
No change in endothelium‐dependent relaxation or morphology of peripheral arteries following 30 days of aortic coarctation.
Authors: Newcomer Sean , Hsu Charlie , Caron Normand , Ingram David , Roseguini Bruno , Laughlin Harold 
Published: June 2021

We designed this study to evaluate the effects of thoracic aortic coarctation (AC) on peripheral endothelial function and development of atherosclerosis. Endothelial function and development of atherosclerosis were assessed in the brachial (BR) and femoral (FEM) arteries of control (CON; n=6) and coarctated (COA; n=7) swine 30 days after AC. In vitro assessments of vasorelaxation to increasing doses of endothelium‐dependent and –independent vasodilators were performed in arterial rings harvested from the BR and FEM arteries. Intimal medial thickness (IMT) and sudan IV staining were performed in the BR and FEM arteries. AC produced a 30 day average blood pressure gradient of 56 ± 5mmHg across the coarctation. Elevated blood pressure proximal to the coarctation produced a significantly greater heart to body weight ratio in the COA (5.51 ± 0.06g/kg) vs. CON (4.66 ± 0.15g/kg) swine. Endothelium‐dependent and ‐independent relaxation was not significantly different in the BR or FEM arteries of COA and CON swine. In addition, there were no significant differences in either IMT or sudan IV staining of the BR or FEM arteries from COA and CON swine. These findings suggest that the stimulus and/or duration of 30 days AC were insufficient to produce endothelial dysfunction and atherosclerosis in the peripheral vasculatures of these swine.Supported by NIH HL083597, HL36088 and HL52490