bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2X7 receptor stimulation raises lysosomal pH and triggers cytokine release from RPE cells
Authors: Guha Sonia , Baltazar Gabriel C , Tu Leigh‐Anne , Lim Jason C , Eysteinsson Thor , Laties Alan M , Mitchell Claire H 
Published: June 2021

Accumulation of lipofuscin in retinal pigmented epithelial (RPE) cell, results from incomplete degradation of phagocytic and autophagic material by lysosomes. Both increased lipofuscin and enhanced cytokine release are associated with macular degeneration in these cells, although the link between the two is unclear. Since stimulation of the P2X7 receptor (P2X7R) activates IL‐1β release in some cell types, and triggers lysosomal exocytosis in others, we investigated the effect of P2X7R activation on lysosomal pH in, and cytokine release from, RPE cells. Surprisingly, stimulation of the P2X7R with agonist BzATP did not lead to a release of IL‐1β but did trigger release of both IL‐6 and MCP‐1. BzATP led to a rise in intracellular Ca2+, and extracellular Ca2+ was necessary for IL‐6 release. Lysosomal pH was elevated by BzATP and this alkalinization was inhibited by P2X7R antagoinsts A438079 and Brilliant Blue G. BzATP on its own did not significantly increase expression of IL‐6, MCP‐1 or the ectoATPase NTPDase1, but did increase expression of all three genes in cells concurrently exposed to oxidized photoreceptor outer segments. In conclusion, stimulation of the P2X7R on RPE cells elevated lysosomal pH and enhanced cytokine release. P2X7R stimulation also upregulated cytokine gene expression in cells subjected to an oxidative challenge.Grant: EY013434
Genetic Mechanisms Coordinating Protein Synthesis and Folding
Authors: Barral Jose M , Siller Efrain , Spencer Paige , Anderson John F 
Published: June 2021

Since the process of translation is directional, nascent proteins emerge from the ribosome as incomplete chains that are susceptible to misfolding. Ribosome movement along an mRNA is influenced by tRNA availability and the physical‐chemical properties of the anticodon‐codon interaction. Experiments from our laboratory suggest that polypeptide elongation rates and local folding events of the nascent protein are intimately coupled. Our current goal is to understand how genetically encoded information regulates protein synthesis rates and folding pathways. Differences in tRNA availability and protein folding efficiencies between bacteria and eukaryotes are being exploited to study these relationships. In order to accelerate or decelerate translation speed, sequences are engineered that encode identical proteins but contain variations along wobble positions of synonymous codons. We find that harmonization of translation rates based on tRNA availability of the organism of origin of the polypeptide with that of the production host leads to robust enhancement of folding efficiencies. These studies provide insight into how the genetic code, although nearly universal in its amino acid encoding properties, is utilized differently between bacteria and eukaryotes to regulate local protein folding events.This work was supported by The Welch Foundation and The Pew Charitable Trusts.
Identification of a Glutathione Transferase Superfamily gene in Leishmania tarentolae
Authors: Osei‐Owusu Nana Yaw , Hearne Jennifer L , Currington Rashalai , Pitula Joseph 
Published: June 2021

Leishmaniasis is a tropical disease that is caused by the parasitic protozoa Leishmania, a member of the Trypanosomatidea family. Unlike other eukaryotes, members of the Trypanosomatidea family lack a complete heme biosynthetic pathway; therefore, they must acquire heme exogenously. The mechanisms of heme scavenging and storage remain to be fully elucidated. Here, it is revealed that one mechanism of these functions may be accomplished through the coordination of heme with glutathione (GSH) via membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG), members of the glutathione transferase (GST) superfamily. It is known that Macaca fascicularis microsomal prostaglandin E synthase type 2 (mPGES‐2), a MAPEG GST, binds GSH which has the potential to form a coordination bond with heme. Therefore, it is reasonable to hypothesize that there is an enzyme similar to mPGES‐2 which scavenges free heme in promastigote Leishmania for use during its maturation. Identification of a GST superfamily member gene target gene in the L. major genome was accomplished using the Basic Local Alignment Search Tool at GeneDB. Because Leishmania lack a complete heme biosynthetic pathway, the exploitation of its heme dependency is a key target for drug discovery. Identification of this gene provides the first evidence of a GST superfamily member in Leishmania.Supported by TEDCO‐MRASC #W81XWH‐07‐2‐0055
Protein Structure Initiative:Biology‐Materials Repository: Developing a Public Resource for Structural Biology Plasmids
Authors: Cormier Catherine , LaBaer Joshua 
Published: June 2021

The PSI:Biology‐Materials Repository (MR; http://psimr.asu.edu) provides centralized archival and distribution of the annotation and samples for plasmids created by the Protein Structure Initiative (PSI). The MR developed an informatics and sample processing pipeline to fully track, sequence analyze, and annotate each plasmid deposited in the MR. Plasmid annotations, including the full length sequence, vector information, and associated publications, are stored in a freely available, searchable database called DNASU (http://dnasu.asu.edu). Each plasmid links to external resources, including the PSI Structural Biology Knowledgebase facilitating cross‐referencing of plasmids to additional protein annotations and experimental data. To expedite and simplify plasmid distribution, the MR developed an Expedited Material Transfer Agreement (MTA) where researchers from network institutions can order and receive PSI plasmids without delay. Currently over 35,000 protein expression plasmids and 75 empty vectors from the PSI are available upon request from DNASU. Overall, this repository of expression‐ready plasmids allows the research community to quickly and easily dissect the biological function of proteins whose structures have been identified by the PSI.This work was supported by the National Institute of General Medical Sciences.
Increases in physical activity reduces BMI gain in Mexican obese girls attending elementary school
Authors: Jauregui Alejandra , Villalpando Salvador , Rangel‐Baltazar Eduardo , Lara‐Zamudio Yaveth , Castro‐Hernández Jessica 
Published: June 2021

BackgroundIn México the prevalence of unhealthy weight jumps from 5% at 5 y to 25% at 7 y, making this a window of opportunity to better understand the pathogenesis of obesity.ObjectiveTo explore the association between PA patterns and obesity over the transition from kindergarten (K) to elementary school (ES) in a cohort of Mexican children.MethodsThe PA (5‐d accelerometry) and BMI of 211 children (5–6 y at the beginning of the study) were measured while in K, 1st and 2nd grade of ES. Associations between PA changes and BMI changes were examined using multiple, longitudinal regression models stratified by sex, controlling for energy intake and other demographic variables.ResultsOverweight/obese girls who had increased their PA level from 1st to 2nd grade ES had a lower BMI gain compared to obese girls who decreased or maintained their PA (0.02 kg/m2, 95%CI: −1.8, 1.9 vs 2.8 kg/m2, 95%CI: 2.2, 3.3, respectively). This association was not observed comparing changes from K to 1st or 2nd grade ES. In boys, changes in PA were not associated with change in BMI.ConclusionIn obese girls, an increase in PA in the early years of ES may result in decreased adiposity overtime.
TAK1 is activated by two independent mechanisms in the regulation of epithelial cell survival
Authors: Takaki Emily Omori , Inagaki Maiko , Mishina Yuji , Matsumoto Kunihiro , Ninomiya‐Tsuji Jun 
Published: June 2021

TAK1 (TGF‐β‐activated kinase 1) is a key signaling intermediate in cytokines such as IL‐1 signaling leading to cell survival. We have previously reported that skin and intestinal epithelium‐specific TAK1 knockout mice are lethal in early neonatal stage due to accumulation of reactive oxygen species and subsequent induction of cell death. TAK1 has three high affinity binding proteins, TAB1, TAB2 and TAB3. TAB3 is structurally very similar to TAB2 and both TAB2 and TAB3 activate TAK1 through recruiting TAK1 to the polyubiquitin chains. TAB1 shares no homology with TAB2/3 and functions to oligomerize and activate TAK1. Although TAB2/3 have been reported to mediate TAK1 activation in cytokine signaling, we found that TAK1 activation was intact in TAB2 and TAB3 double‐deficient cells in response to IL‐1. Unexpectedly, we discovered that TAK1 activation was abolished in TAB1 and TAB2 double‐deficient cells. Furthermore, epithelium‐specific TAB1 and TAB2 double but not TAB1 or TAB2 single knockout mice phenocopied epithelium‐specific TAK1 knockout mice. TAK1 kinase activity was abolished in TAB1 and TAB2 knockout in vivo epithelial tissues, while it was maintained in TAB1 or TAB2 single knockout epithelium. These results demonstrate that TAB1‐ and TAB2‐mediated mechanisms independently activate TAK1 in the in vivo epithelial cells, and one mechanism is sufficient for maintenance of TAK1 activity.This work was supported by National Institutes of Health Grant GM068812 and GM084406 (to J. N‐T.)
Vitamin D2 enriched mushrooms significantly reduced inflammatory cytokine and chemokine expression in the spleens of LPS challenged rats
Authors: Babu Uma S. , Garthoff Larry H. , Balan Kannan V. , Calvo Mona S. 
Published: June 2021

Vitamin D2 (VitD) from UVB‐exposed mushrooms (MR) has been shown to stimulate natural killer cell activity and modulate plasma cytokine response to lipopolysaccharide (LPS) challenge in rats. In this study, female rats were fed 1 of 5 diets for 10 weeks followed by challenge with pyrogen‐free saline or a low dose of LPS (100 μg/kg BW). All 5 experimental diets were based on AIN‐93G formulation with varying levels of VitD: 1) control levels of VitD; 2) no VitD; 3) no VitD + 5% unexposed MR; 4) no VitD + 2.5% UVB‐exposed MR, and 5) no VitD + 5% UVB‐exposed MR. Spleens were evaluated by microarray (Qiagen, Frederick, MD) for changes in expression of inflammatory cytokines and their receptors 3 h following LPS challenge. Several inflammatory chemokines, including Ccl2, 3, 4, 7 and 9, as well as Cxcl1, 2, 6, 9, 10 and 11 and cytokines, including interferon‐γ, IL‐1α and IL‐10 were significantly up‐regulated in spleens of LPS treated rats from all the dietary groups compared to those treated with saline. However, this up‐regulation was significantly reduced in the VitD enriched mushroom groups (2.5% & 5% UVB‐exposed MR) compared to those fed the control diet, no VitD‐control diet or 5% unexposed MR diet.ConclusionsMicroarray analysis of spleens confirmed earlier findings that rats fed UVB‐exposed MR diets with higher VitD experienced significant immune modulation with anti‐inflammatory effects.
The expression, purification, and crystallization of the HNOX regulatory domain of bovine soluble guanylate cyclase
Authors: Taylor Leida , Garcin Elsa D 
Published: June 2021

Soluble guanylate cyclase (sGC) converts GTP to cGMP, which plays a crucial role in vasodilation. The β subunit contains a heme NO/oxygen‐binding (HNOX) domain. NO binding to HNOX likely induces a conformational change leading to sGC activation. We aim to elucidate the mechanism of sGC activation using structural studies.Our early results revealed that the β193‐HNOX construct is poorly expressed in E. coli. To solve this problem, we made 12 truncations (from residues 187 to 198) by site‐directed mutagenesis. Cells were transformed with all 12 mutant plasmids and expression conditions were tested. We found that 3 constructs were expressed at high levels, and that only 2 proteins were soluble. Ion exchange and size exclusion chromatography yielded large amounts of partially pure samples. The UV/Vis spectra of both proteins revealed that the heme pocket is intact and that NO is bound to the heme. We are now using immunoaffinity purification to improve the sample purity and attempt crystallization.In summary, we used a systematic mutagenesis approach to obtain novel bovine HNOX sGC constructs with high levels of expression and solubility in E. coli. These constructs will be key to solve the first x‐ray structure of a mammalian HNOX domain that will provide a structural basis to understand the mechanism for NO activation.Work supported by American Heart Association Scientist Development Grant (E. Garcin)
Characterization of next‐generation anti‐androgens as potential prostate cancer therapeutics
Authors: Jobbagy Soma , Sikes Robert Allen , Koh John Tze‐tzun 
Published: June 2021

Anti‐androgens are the gold standard of care for treatment of advanced prostate cancer (PCa). The purpose of this study was to characterize novel anti‐androgens PLM1, PLM6, and PAN52 designed and synthesized in the Koh laboratory. PLM6 and PAN52 but not PLM1 are thought to have unique mechanisms of action based on their ability to evade progression to anti‐androgen resistance in vitro. Western blot analysis of nuclear fractions showed correlation between prevention of AR nuclear translocation and progression of anti‐androgen resistance in prostate cancer cell lines. Some differences in localization effects were also observed between LNCaP and CWR22Rv1 PCa models that may reflect AR mutants present in these cell lines. The compound PLM6 and PAN52 found to down‐regulate the androgen receptor (AR) in PCa cell lines. These compounds thus appear to hold promise as therapy for advanced prostate cancer.This work funded by the Beckman Foundation and the National Institutes of Health 5R01DK054257
EFFECT OF VISCUM ALBUM ON METOCLOPRAMIDE (MAXOLON) INDUCED HYPERPROLACTINEMIA AND HEPATOTOXICITY
Authors: Nwoke Stella C , Magbagbeola Olubunmi A , Ebuehi Albert O , Afolayan A T 
Published: June 2021

The use of herbal concoctions for the management of infertility by Nigerian women is becoming a common trend. One of these herbal plants used is Viscum album. This research work studied the reversal effect of Viscum album on metoclopramide (maxolon) induced hyperprolactinemia and hepatotoxicity.The level of Prolactin, Aspartate Aminotransferse (AST) and Alanine Aminotransferase ALT) activities were assayed in 25 female albino rats, which were divided into 5 equal groups. Group 1 control, while group 2 (negative control) treated with maxolon alone, group 3, 4 and 5 animals treated with maxolon, for 7 days, then treated with 62.5g, 125g and 250g of Viscum album extract respectively.The result showed a significant increase (P< 0.05) in prolactin level (32.36ng/ml) in group 2 animals compared to the control group 1 (12.36ng/ml), while its level decreased in group 3, 4, 5 respectively (23.24ng/ml, 16.06ng/ml, 13.40 ng/ml).The value of serum ALT of group 2 (25.00U/I) significantly increased (P < 0.05) as compared to group 1 (17.20U/I) while in group 3, 4, and 5, no significant increase in ALT was observed (20.40U/I, 20.00U/I, 21.40U/I). Activity of AST in group 2 animals (35.80U/I) was high as compared to the control group (27.60U/I) while in group 3, 4, and 5, the AST activity reduced.In conclusion, the results show the overall effect of Viscum album extract was dose dependent, hepatoprotective and has hypoprolactinemia.
Manual Activities of Meal Preparation and Consumption Play a Significant Role in Musculoskeletal Nutrient Intake among Homebound Older Adults
Authors: Sharkey Joseph R 
Published: June 2021

PurposeMusculoskeletal nutrients (MN) – vitamin D, calcium, magnesium, and phosphorus – are associated with lower extremity physical function (balance, mobility, and strength) and with performance of basic tasks of daily living. Considering that manual, daily activities that involve meal preparation and consumption (AMPC) are important to older adults, especially those who are homebound, this study examined the influence of difficulties in nutrition‐related AMPC on usual intake of MN.MethodsSelf‐reported measures at baseline (demographic, psychosocial and health‐related factors, dietary intake of MN from 3 24‐hour dietary recalls, and seven nutrition‐related manual AMPC tasks) from a randomly recruited sample of 345 homebound older adults were examined. Ordered logistic regression was used to evaluate the relationship between level of difficulty in AMPC and dietary intakes <2/3 age‐ and gender‐specific Recommended Dietary Allowance/Adequate Intake (RDA/AI) in vitamin D, calcium, magnesium, and phosphorus.ResultsAlmost 30% (n = 102) found 1–2 AMPC were very difficult/impossible; 13.9% (n = 48) reported ≥3 of 7 AMPC. Dietary intake <2/3 RDA/AI was reported by 92% for vitamin D, 72% calcium, 59% magnesium, and 3% phosphorus. Forty‐three percent reported <2/3 RDA/AI for 1–2 of the 4 MN; 52% for 3–4 MN. Independent of other factors, increased number of MN <2/3 RDA/AI was associated with gender, education, and difficulty ≥3 AMPC [odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.1–4.1].ConclusionsThis study suggests that manual activities of meal preparation and consumption may play a significant role in MN intake. As such, future interventions should focus on improving AMPC and the type of food containers used by older adults, which may also improve nutritional health and quality of life.
Effects of whole and refined grains on cardiometabolic risk factors: designing a controlled‐feeding study
Authors: Harris Kristina Arline , West Sheila , Heuvel Jack Vanden , Kris‐Etherton Penny 
Published: June 2021

Dietary recommendations to reduce risk of major chronic diseases consistently include the substitution of whole grains for refined grains. However, the strength of evidence to support this is “moderate” due to reliance on epidemiological data and mixed results from free‐living clinical trials. Therefore, a 12‐week randomized, parallel‐arm, controlled‐feeding, weight‐loss study was designed to determine the biological effects of chronic whole and refined grain intake on cardiometabolic risk factors in participants with “pre‐metabolic syndrome (MetSyn).” Overweight or obese (BMI 25–42 kg/m2) men (n=25) and women (n=26) aged 35–55 with increased waist circumference and at least 1 other MetSyn characteristic were randomized to either a whole (WG) or refined grain (RG) diet. Weight was maintained for 6 weeks then weight loss was induced for 6 weeks via reduced‐calorie diet (~500 kcal/d). The macronutrient profiles of WG and RG diets were matched (~54% CHO, ~17% PRO, ~29% FAT, ~6.7% SFA) with the exception of fiber due to the whole grains (WG: 7 serv WG/d, 39 g fiber/d; RG: 0 WG serv/d, 22 g fiber/d in 2100 kcal/d diet). We hypothesize that a diet containing whole versus refined grains will elicit improvements in abdominal adiposity, inflammation, and endothelial function, which are clinical targets of cardiometabolic disease that present in MetSyn. This study is supported by General Mills.Grant Funding Source: General Mills
The influence that the fractions reaches to the antiobesity key enzyme when partitioning the green pepper water extracts according to a solvent
Authors: Baek Jongmi , Kim Taewoo , Kim Jeongmi , Kim Taehyuk , Choe Myeon 
Published: June 2021

We measured an effect by using the enzyme activity of the antiobesity key enzyme. Lipoprotein lipase (LPL) catalyses the hydrolysis of the triacylglycerol component of circulating chylomicrons and very low density lipoproteins, thereby providing non‐esterified fatty acids and 2‐monoacylglycerol for tissue utilisation. Also activation of fatty acids by acyl‐CoA synthetase(ACS) and carnitine acetyl transferase(CAT) enzymes is required for de novo lipid synthesis, fatty acid catabolism, and remodeling of biological membranes. It is known that the capsaicin of the red pepper controls a fat already and there is an effect. But we result of partitioning the water extracts of the green pepper according to a solvent and evaluating that, the antiobesity effect was exposed to be shown in the fractions using the water. Therefore, the antiobesity effect of the green pepper is considered to be besides a capsaicin.Thanks to financially support the Economy(MKE) through the fostering project of the Human Resource Training Project for Regional Innovation.
The effect of an emulsified fish oil preparation on cardiovascular risk factors in an overweight young adult population
Authors: Root Martin , McGinn Megan , Collier Scott , Zwetsloot Kevin 
Published: June 2021

BackgroundLong chain omega‐3 fatty acids (O3) are known to have beneficial effects on a number of hemodynamic and vascular risk factors in at‐risk populations. The effects of a highly bioavailable emulsified preparation on a young adult population were less well known.MethodsYoung adults, age 18–30, with body mass indices (BMIs) greater than 23 (average = 28.1) were administered 1.7 g of fish oil O3 per day in an emulsified preparation (N=30) (Coromega, Inc.) or safflower placebo (N=27) for 4 weeks in a double‐blind randomized design. Blood was drawn and anthropometric measurements taken before and after the dosing period. Central pressures, arterial distensibility, inflammatory cytokines, fasting serum lipids, glucose, and C‐reactive protein were measured.ResultNone of the 5 American Heart Association metabolic syndrome measures improved over the dosing period. None of the hemodynamic measures (pulse wave velocity, augmentation index, or aortic systolic blood pressure), inflammatory cytokines (IL‐6, IL‐8, IL‐10, or TNF‐α), C‐reactive protein, or lipids (LDL, HDL, or triglycerides) improved over the dosing period.ConclusionsThese data suggest that O3 supplementation has no effect in this relatively healthy overweight cohort. This may be due to the relatively short supplementation time.
Pinto beans as part of a normal diet do not improve glycemic control in adults with type 2 diabetes
Authors: Hutchins Andrea , Winham Donna 
Published: June 2021

This study examined the impact of daily consumption of ½ c pinto beans, compared to a control (½ c green beans), on changes in fasting glucose, postprandial glucose and HbA1c concentrations in men and women with type 2 diabetes (controlled by diet or metformin). Although some health professionals are promoting the benefits of dry beans for glucose control, confusion exists regarding the glycemic properties of dry beans in the context of a normal diet. After a baseline wash‐in period, 16 subjects were randomly assigned to 2 treatment periods [control period and pinto beans], each 12‐weeks in duration with a 4‐week wash‐out period. Eight subjects completed both treatment periods. During the wash‐in period and interventions, on days a diet record was kept (28 total days), subjects measured a postprandial capillary glucose concentration using a glucometer (provided by study) 1 hour after the meal during which the pinto beans or control were consumed. Before and after each intervention, subjects provided a fasted venous blood sample for glucose and HbA1c analyses. There were no statistically significant changes (p<0.05) in fasting glucose, HbA1c or average postprandial glucose values between the 2 interventions. The results of this study did not demonstrate improved glycemic control when pinto beans were incorporated into the normal diet of men and women with type 2 diabetes.Research was supported by the US Dry Bean Council.