bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyisoprenylated Cysteinyl Amides Induce Apoptosis and Inhibit Proliferation and Migration of Human K‐Ras Mutant Cancer cells
Authors: Nkembo Augustine , Salako Olufisayo , Poku Rosemary , Aguilar Byron , Flores‐rozas Hernan , Lamango Nazarius 
Published: June 2021

Activating K‐Ras is present in 90, 50 and 25% of pancreatic, colorectal and lung cancers, respectively, making them refractive to chemotherapies. Tumors with Ras mutations are challenging to drug, leading to poor prognoses. We hypothesize that polyisoprenylated cysteinyl amides inhibitors (PCAIs) can be effectively used to target and disrupt Ras signaling resulting in potentially very effective new therapies. To test this, MIAPaCa‐2, Panc10‐05, Caco‐2 and A549 human cancer cells were treated with PCAIs for their effects on cell viability, proliferation, apoptosis and migration. The PCAIs inhibited MIAPaCa‐2, Panc10.05, Caco‐2 and A549 cell viability and proliferation with EC50 values ranging from 2.0 to 6.0, 1.8 to 3.3, 0.2 to 4.0 and 0.4 to 10 µM, respectively. Ethidium bromide/acridine orange analysis suggests an apoptotic cell death mechanism while annexin v/propidium iodide flow cytometry analysis revealed cell arrest at the G0/G1 phase. Submicromolar concentrations of PCAIs significantly inhibited MIAPaCa‐2 cell migration in the wound‐healing assay. The effect on migration appeared to be linked to the disruption of filamentous actin organization as observed with phalloidin staining and transfections with a plasmid expressing an RFP‐tagged F‐actin marker protein. The potency of PCAIs in K‐Ras mutant cells is likely due to the disruption of signaling by Ras and related monomeric G‐proteins such as RhoA/B. PCAIs might therefore represent attractive therapeutic molecules for cancers with activating Ras mutations and hyperactive G‐proteins.Supported by the NIMHD of the NIH under Award Number G12 MD007582
Regulation of Ubiquitin Independent Proteasomal Degradation of Intrinsically Disordered Proteins
Authors: Shaul Yosef 
Published: June 2021

Intrinsically disordered proteins (IDPs) are labile proteins and undergo degradation by ubiquitin dependent and independent mechanisms. Previously we reported on the 20S proteasomal degradation pathway of the IDPs that is regulated by NQO1, a 20S associated protein, and by Nannies. Nannies are IDP interacting proteins functioning to inhibit IDPs proteasomal degradation. However the question of whether and how the IDPs are targeted to the 20S proteasome remained open. To address this question, we adopted the BiFC cell based technique for visualizing protein interactions with 20S proteasome. We found that IDPs interact with a subset of 20S proteasome alpha subunits. The results suggest that the 20S proteasome has two hub sites for interaction with IDPs in the alpha ring. We focused on the subunit PSMA3 and showed that its C terminus interacts with multiple IDPs. Thus, it implies that IDPs are targeted to the 20S proteasome prior to their degradation. In addition, lately we have identified a new type of 26S proteasomes whereby no ATP but NADH regulates its assembly. We have evidence for this new type of NADH‐26S proteasomes preferentially involved in IDPs degradation. Finally we will report on a new proteomic approach in identifying the selective 20S proteasomes substrates.Asher, G., Reuven, N. and Shaul, Y. (2006). 20S proteasomes and protein degradation by default. BioEssay. 28(8):844‐849.Tsvetkov, P., Reuven, N. and Shaul Y. (2009). The nanny model for IDPs. Nat Chem Biol. 5(11):778‐81Tsvetkov P, Myers N, Eliav R, Adamovich Y, Hagai T, Adler J, Navon A, and Shaul Y. (2014). NADH Binds and Stabilizes the 26S Proteasomes Independent of ATP. J Biol Chem. Apr 18;289(16):11272‐81.
The Perinuclear Endoplasmic Reticulum as the Site of Phosphatidylethanolamine Synthesis in a Model Eukaryote
Authors: Buetikofer Peter , Farine Luce 
Published: June 2021

Phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are among the most abundant phospholipids in biological membranes. In many eukaryotes, the CDP‐ethanolamine and CDP‐choline branches of the Kennedy pathway represent major – and often essential –routes for the production of PE and PC, respectively. While ethanolamine and choline phosphotransferases (EPT and CPT, respectively) catalyze the last reactions in the respective pathways, choline/ethanolamine phosphotransferase shows dual specificity for both CDP‐ethanolamine and CDP‐choline as substratesAlthough the site of PE and PC synthesis is commonly known to be the endoplasmic reticulum (ER), detailed information on the localization of the different phosphotransferases is lacking. In the unicellular model eukaryote, Trypanosoma brucei, both branches of the Kennedy pathway are essential for parasite growth in culture, making T. brucei an ideal organism to study eukaryotic phospholipid synthesis. We have previously reported that EPT catalyzes the production of alk‐1‐enyl‐acyl PE molecular species while CEPT synthesizes diacyl‐type PE and PC molecular species. We now show that the two enzymes localize to different sub‐compartments of the ER. By expressing a series of tagged EPT and CEPT enzymes in T. brucei parasites, EPT was found exclusively in a distinct area located close to but different from the nuclear membrane, which we term perinuclear ER. In contrast, CEPT was detected in the bulk ER. The different localization pattern of EPT and CEPT was confirmed by subcellular fractionation experiments in combination with enzyme activity measurements and identification of the tagged proteins by immmunoblotting.
Characterization of Human Polyamine Oxidase
Authors: Zamora Diana , Tormos Melendez Jose , Galaleldeen Ahmad 
Published: June 2021

Polyamine Oxidase (PAO) is a flavoprotein that is necessary for the catabolism of polyamines. PAO oxidizes the endo carbon nitrogen bonds of N1‐acetylspermine and N1‐acetylspermidine when oxidized to spermine and spermidine, respectively. Normal levels of polyamines are needed for cell growth, yet their actual function is not well understood. The crystal structures of maize and yeast PAO (Fms1) are available but no mammalian PAO structure has been determined to date. The identity between human PAO (hPAO), Fms1, and maize PAO is only 20%. Sequence homology and mutational analysis showed that a conserved histidine residue in mammalian PAOs that corresponds to position 67 of Fms1 helps to properly position the amine substrate for oxidation. Determining the crystal structure of hPAO will help identify the other residues that play a role in substrate binding and catalysis.hPAO was cloned into pAG8H, a modified pET19d vector that introduces a cleavable his‐tag at the N‐terminus of the protein. hPAO was expressed and purified using affinity and ion exchange columns. The his‐tag was removed and the protein is being assayed for activity. Analytical ultracentrifugation sedimentation velocity experiments are also underway to determine the oligomerization state of the protein in solution in addition to crystallization trials to determine the structure of hPAO.
Replacement of Sugar‐Sweetened Beverages with Water and its Impact on Insulin Sensitivity Among Overweight Adolescents and Young Adults
Authors: Jin Ran , Collin Lindsay , Vos Miriam , Welsh Jean 
Published: June 2021

BackgroundIntake of sugar‐sweetened beverages (SSBs) has dramatically increased over recent decades. Habitually high consumption of SSB has beenlinked to multiple adverse health consequences including insulin resistance. High consumers are encouraged to reduce their SSB consumption and drink more water in their place but little is known about the impact of this replacement.ObjectiveWe aimed to evaluate whether 1‐month replacement of SSBs with plain water would improve insulin sensitivity.MethodsA total of 22 overweight males and females age 16‐21 y, who consumed 蠅 3 servings of SSBs daily at baseline, were recruited in a 1‐month cross‐over beverage trial. All subjects were instructed to replace all sweet beverages (SSBs, diet drinks, juices) with study providedbottled water (3 daily) for 1 month and otherwise maintain their diet and activity level as usual. Their plasma levels of glucose and insulin sensitivity were compared at baseline and after one month of water replacement, using Wilcoxon test (SPSS, version 17.0, SPSS Inc., Chicago, IL). Insulin sensitivity was assessed by calculating HOMA‐IR (fasting glucose * insulin / 405) and adipose IR (fasting insulin * free fatty acid).ResultsAfter the replacement of their sugar‐sweetened beverages with plain water for 1 month, subjects had reduced concentration of plasma glucose (p = 0.048), and improved insulin sensitivity as indicated by both HOMA‐IR (p = 0.042) and adipose IR (p = 0.050).ConclusionThe results of this study suggest that insulin sensitivity and plasma glucose level regulation among overweight high consumers improves after one month of replacing SSBs with water and in the absence of other changes in diet or physical activity.
HYDRAGUT study: Influence of HYDRAtion status on the GUT microbiota and their impact on the immune system.
Authors: Redondo Useros Noemi , Gheorghe Alina , Serrano Labajos Ruth , Nova Rebato Esther , Marcos Sanchez Ascension 
Published: June 2021

While a good hydration state is essential for health maintenance, the dehydration state, produced by the imbalance between fluid intake and fluid losses, could be related to an inflammatory situation. A good mucosal hydration is also necessary for a normal protective intestinal barrier. We performed this study in one hundred twenty‐three healthy young adults from Madrid to address the influence of hydration status on the gut microbiota balance and their impact on the immune system. Blood and stool samples were collected from all volunteers. Beverage patterns, sodium and osmolality levels, intestinal microbiota, leukocyte subpopulations and cytokine levels were analysed.Men showed statistically higher levels of osmolality and liquids intake than women (P<0.05), and osmolality had a significant positive correlation with beer intake in men and with soft drink intake in women (P<0.05). Men showed a trend to increased values of hydration parameters with TNF‐α rises. Sodium levels were influenced by Bacteroidetes (P=0.029), whereas Clostridium affected osmolality levels (P=0.043), suggesting an influence on cellular transport of solutes and thus contributing to the hydration state.Bifidobacterium composition influenced T lymphocytes levels (P<0.001), reflecting an interaction with the immune response of the host. It might be interesting to evaluate this effect in euhydration and dehydration states, and thus relating possible changes in dehydration biomarkers with changes in microbiota community and the immune response.
Grit is Negatively Associated with Body Weight, Body Mass Index and Disinhibition and Positively Related to Cognitive Eating Restraint
Authors: Metzgar Catherine , Nickols‐Richardson Sharon 
Published: June 2021

Grit, the perseverance and passion for pursing long‐term goals, may be a personality trait of interest in weight management as grit may be related to body weight (BW) modification through the control of food intake. This study explored the association between grit and cognitive eating restraint (CER), disinhibition and hunger, three factors known to affect BW regulation. Eighty women [mean±SD age: 31.4±8.2 y, BW: 76.2±19.1 kg, body mass index (BMI): 27.9±6.9 kg/m2] completed the Short Grit Scale (Grit‐S) and Eating Inventory (EI) upon enrolling in a 1‐year weight gain prevention trial. Grit‐S scores ranged from 2.0 to 4.6 (1‐5 scale); the average Grit‐S score was 3.4±0.7. EI scores for CER (0‐21 items), disinhibition (0‐16 items) and hunger (0‐14 items) ranged from 2‐17, 1‐14 and 0‐13, respectively, with average scores of 9.1±3.5, 7.6±3.2 and 5.6±2.8, respectively. Pearson's correlation was used to examine the relationship between Grit‐S score and BW, BMI, CER, disinhibition and hunger. Grit was negatively associated with BW (r=‐0.24, p<0.05), BMI (r=‐0.23, p<0.05) and disinhibition (r=‐0.47, p<0.01) and positively associated with CER (r=0.23, p<0.05). There was no significant relationship between grit and hunger. These findings suggest that women who have a higher Grit‐S score may have better control of BW management as reflected in lower BW and BMI, higher level of CER and lower level of disinhibition. Further research is warranted to understand whether grit may be a useful predictor of BW status, prevention of BW gain, attainment of BW loss and/or success with BW‐loss maintenance.Funded by an Illinois Agricultural Experiment Station/National Institute of Food and Agriculture research grant (#100125).
Quenching of Cytotoxic Reactive Carbonyl Species by Black Rice with Giant Embryo
Authors: Colzani Mara , Lee Yoon‐Mi , Han Sang‐Ik , Aldini Giancarlo , Yeum Kyung‐Jin 
Published: June 2021

Reactive carbonyl species (RCS) are cytotoxic molecules originating from lipid peroxidation and sugar oxidation. A robust and efficient method based on high resolution mass spectrometry was used to test the ability of water‐soluble rice extracts to inhibit protein carbonylation induced by RCS. The model protein ubiquitin was incubated in vitro with different RCS such as 4‐hydroxy‐trans‐2‐nonenal (HNE) in presence of increasing concentration of various rice extracts. After 24 hours of incubation, the reaction was stopped and ubiquitin was analyzed by HRMS to determine the extent of protein modification due to the RCS, and to observe its modulation in presence of the extracts. The different rice extracts inhibited the formation of RCS‐induced protein modificationsto different extents. A black sticky rice with giant embryo (IC50=~29.1) strongly inhibited protein modification by the HNE than white rice (IC50=~151.0). These findings suggest that certain bioactive components in water‐soluble fractions of specific rice varieties effectivelysequester RCS, and that such rice variety can be valuable for dietary strategy for optimal health.This work was supported by Rural Development Administration (PJ010059), Republic of Korea.
Association between ApoE (rs429358 and rs7412), SLC16A11 (rs13342692) and ABCA1 (rs9282541) polymorphisms and biochemical parameters in subjects with metabolic syndrome
Authors: Orozco‐Ruiz Ximena , Guevara‐Cruz Martha , Ayala‐Alanis Brenda , Medina‐Vera Isabel , Jimenez‐Rolland Edith , Aguilar‐Lopez Miriam , Tovar Armando , Torres Nimbe 
Published: June 2021

Approximately one of two Mexican adults have metabolic syndrome (MetS). Some single nucleotide polymorphisms (SNPs) highly prevalent in the Mexican population, particularly ApoE, SLC16A11 and ABCA1 SNPs have been associated with dyslipidemia, diabetes and obesity. Thus, the aim of this work was to study the association of these SNPs with the presence of several factors of MetS.We studied 880 Mexican overweight and obese subjects (164 men, 716 women). The frequency of ApoE, SLC16A11 and ABCA1 were 25.5%, 64.4% and 20.6% respectively. Subjects with the ApoE or SCL16A11 or the presence of both showed a higher waist circumference, serum triglycerides (TG), glucose, total cholesterol, blood pressure (BP) and lower HDL cholesterol (HDL‐C). Patients with MetS and ABCA1 SNP showed higher TG and BP and lower HDL‐C than those without MetS. Subjects with MetS and three SNPs showed higher TG (249 mg/dl) and lower HDL‐C (32 mg/dl). Interestingly subjects with ApoE and SCL16A11 or ApoE and ABCA1 had 1.5 fold more risk to develop MetS. Thus, the presence of specific gene variants could increase the risk to have MetS and possibly the risk of cardiovascular disease.Supported by: MEDIX to NT and CONACYT 181685 to MGC
Impact of Liquid Sugar Reduction on Behavioral and Brain Responses to Food Viewing
Authors: Crézé Camille , Bielser Marie‐Laure , Knebel Jean‐François , Campos Vanessa , Tappy Luc , Murray Micah , Toepel Ulrike 
Published: June 2021

Obesity is increasingly considered as a brain disease in which homeostatic mechanisms regulating food intake are overridden by hedonic drives towards consumption of foods high in fat and sugar. How added sugars from sugar‐sweetened beverages (SSBs) impact hedonic drives to foods, and whether artificial sweeteners have specific effects of their own remains unknown.We studied 14 high SSB consumers (8 men, 6 women) before and after 3 months of SSB replacement by artificially sweetened equivalents. Participants performed behavioral preference ratings on a 5‐point scale when presented with color images of solid foods differing in fat content (high‐ vs. low‐fat) and taste quality (savory vs. sweet). Moreover, the spatio‐temporal brain dynamics while viewing the food types were assessed using electroencephalography (EEG) and electrical neuroimaging analyses.Behavioral results show a significantly greater appreciation of savory foods, but decreased appreciation of sweet foods post‐SSB replacement. Brain responses reveal diet‐induced modulations in particular to low‐fat foods in areas involved in food valuation and cognitive control over food intake. That is, the replacement of liquid calories substantially influences responsiveness to solid calories, likely explaining changes in food intake behavior. Whether these effects are due to sugar reduction or to artificial sweeteners per se remains to be investigated.This work was supported by the Swiss National Science Foundation.
Potential Role of PYY in Skeletal Muscle Cells?
Authors: Gupta Diwakar , Roman Heather , Touhamy Samir , Lin Kevin , Thalacker‐Mercer Anna 
Published: June 2021

PYY is characteristically considered an appetite hormone with identified roles in metabolism, inflammation, and proliferation. The expression of PYY and its receptors has been demonstrated in the skeletal muscle; however, the role of PYY in the skeletal muscle is unknown.ObjectiveTo investigate the role of PYY on proliferating and differentiating/differentiated skeletal myoblasts and to determine the effect of PYY on inflammatory and metabolic signaling pathways.MethodsExpression of the PYY gene was determined in cultured murine C2C12 cells incubated in growth or differentiation media (GM and DM, respectively) using quantitative PCR. Additionally, changes in proteins of interest were determined from C2C12 cells that were cultured in DM for 96 h then switched to DM containing 0.1 mM palmitate for 72 h, followed by exposure to 500 pM murine PYY3‐36 for 6 h prior to lysis.ResultsPYY gene expression, which was identified in proliferating C2C12 cells, decreased in differentiating cells. Relative to myotubes that received only palmitate, the presence of PYY decreased phosphorylation of STAT3 (signal transducer and activator of transcription 3) serine‐727 (‐37%, p = 0.03) and tyrosine‐705 (‐33%, p = 0.01). There was no change in the total STAT3 protein, the ratio of phospho‐STAT3 to total STAT3, or NF‐kB‐p65 levels.ConclusionsThese results indicate that the PYY gene is not only detectable in mouse myoblasts, but it also changes with different physiological states (i.e. proliferating vs. differentiating). Additionally, PYY appears to play a role in skeletal muscle STAT3 signaling. Follow‐up research is necessary to confirm these results and identify downstream targets of PYY through the STAT3 pathway and functional outcomes. Support: NIDDK P30DK056336
Influence of açaí supplementation in cardiac remodeling after myocardium infarction in rats
Authors: Figueiredo Amanda , Polegato Bertha , Cardoso Ana Carolina , Candido Renata , Rafacho Bruna Paola , Dos Santos Priscila , Batista Diego , Gonçalves Andréa , Okoshi Katashi , Gaiola Paula , Zornoff Leonardo , Minicucci Marcos , Paiva Sergio Alberto 
Published: June 2021

One of the determining factors for cardiac remodeling after myocardial infarction (MI) is oxidative stress. Fruits, such as açaí, which modulate oxidative stress, may attenuate cardiac. (Vissotto, 2013)Objectiveanalyze the influence of açaí supplementation in chow on the cardiac remodeling after MI.Material and methodsAfter MI, male rats Wistar weighing from 200 g were allocated into 6 groups: 1) Sham group fed with standard chow (SA0, n=5); 2) Sham group fed with standard chow with 2% açaí (SA2, n=5); 3) Sham group fed with standard chow with 5% açaí (SA5, n=5); 4) MI standard chow (IA0, n=5); 5) MI and chow with 2% açaí (IA2, n=7); 6) MI and chow with 5% açaí (IA5, n=7). After 3 months of supplementation, echocardiography study was conducted. Two‐way ANOVA was used and values are expressed as mean±SE.ResultsAfter 3 months, the Infarct size did not differ among the MI groups. In MI rats, it was observed an increase in the left ventricular diastolic diameter, left ventricular systolic diameter, left ventricle posterior wall thickness, left atrial diameter (LA)/ aortic diameter (Ao) and a reduction in the fractional area change and A mitral wave. The addition of açaí pulp in the diet reduceLA (LA, LA/Ao, LA/BW), increase A mitral wave andreduce the E mitral wave and E/A. No difference was observed between IA2 and IA5.Conclusionaçaí supplementation modulates cardiac remodeling induced by MI, improving the diastolic function.
Thrombomodulin Inhibits Tissue factor Mediated Thrombin Generation in blood and Prothrombin Complex Concentrates
Authors: Fareed Jawed , Hoppensteadt Debra , Syed Daneyal , Kahn Daniel , Mosier Michael , Kaul Inder 
Published: June 2021

A recombinant thrombomodulin (Recomodulin, Asahai Kasei, Tokyo, Japan) is currently used for the management of DIC and related disorders. Beside inhibiting thrombin and forming complexes with this enzyme, Recomodulin (RM) mediates its therapeutic effects involving modulation of inflammatory processes and thrombogenesis. The purpose of this study is to determine the effect of RM on thrombin generation in plasma and prothrombin complex concentrates.RM (2.02 mg/ampule) was commercially obtained. Working solutions of buffered RM were prepared at 100ug/ml. Tissue factor mediated generation of thrombin and its inhibition in normal human plasma (NHP) (n=25), platelet rich plasma (PRP) (n=25) and various prothrombin complex concentrates such as Beriplex, Cofact, Feiba, Konyne, Octaplex, Preconativ, Profilnin, Prothromplex ( 1u/ml) were investigated utilizing a fluorometric thrombokinetics method. The effect of RM on thrombin mediated fibrinokinetics was also measured using an optical method.RM produced a concentration dependent inhibition of thrombin generation in all systems. In the NHP the IC50 was 0.29 + 0.06 ug/ml in contrast to PRP where the IC50 was 1.99 + 0.31 ug/ml. The inhibition of thrombin generation in various PCCs was also concentration and product dependent. Marked inhibition was noted in Preconativ, Prothromplex and Beriplex. RM also inhibited the fibrin formation in both the PRP and NHP system in a differential manner.These results suggest that beside the direct inhibition of thrombin, RM is capable of inhibiting thrombin generation in a matrix dependent fashion and is also capable of modulating fibrin formation as evident by fibrinokinetic studies.