bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of the activity of Estrogen Response Elements present on Pax‐5 promoter and their potential role on regulating Pax‐5 expression in breast cancer
Authors: Faye Mame Daro , Ouellette Rodney 
Published: June 2021

Pax‐5 is a transcription factor playing a crucial role in B lymphopoïesis and its deregulation has been associated to certain malignancies, namely non‐Hodgkin lymphomas and acute lymphoblastic leukemia. Although Pax‐5 is mainly known to be expressed in B cells, there is a body of preliminary data generated in our laboratory suggesting its expression in some breast cancer cell lines and primary breast tumors.In an attempt to explain Pax‐5 expression in these breast cancer cases, we analyzed its promoter and found a number of Estrogen Receptor Elements (EREs) and Estrogen Related Receptors sites (ERRs), suggesting a role for estrogen receptors in Pax‐5 expression in breast cancer. Therefore, electrophoretic mobility shift assays (EMSA) were performed to assess the binding capacity of estrogen receptors ERα and ERβ on those predicted sites, which were also cloned in the Luciferase reporter vector pGL3‐Promoter to evaluate the receptors activity by dual luciferase reporter assays.We report here the specific binding of estrogen receptors on some of the EREs located on Pax‐5 promoter and their differential activation under 17β‐estradiol stimulation in MCF‐7 cells. These results suggest a role for estrogen receptors in the expression of the oncogene Pax‐5 in breast cancer and suggest a mechanism that contributes to breast carcinogenesis.This work has been supported by an ''Atlantic Innovation Fund'' grant.
AMP‐activated Protein kinase regulates FasL expression in Jurkat T lymphocytes via NF‐AT and AP‐1 dependent pathways
Authors: Lee Jung Yeon , Kang Insug 
Published: June 2021

T cell activation by T cell receptor (TCR) engagement or its pharmacological mimics induces FasL expression to maintain T cell homeostasis by apoptosis of activated T cells. AMP‐activated protein kinase (AMPK), an important regulator of energy homeostasis, is known to be activated during T cell activation. In this study, we examined the roles and signaling mechanisms of AMPK in T cell receptor‐induced FasL expression. AMPK is activated at the downstream of Ca2+/CaMKK during T cell receptor activation. Inhibition of AMPK by pharmacological agent or small interfering RNA suppressed FasL expression as well as secretion of FasL protein in T cells stimulated with PMA plus ionomycin (PMA/Io) or with monoclonal anti‐CD3 plus anti‐CD28 (CD3/CD28). Consistently, inhibition of AMPK blocked promoter activity of FasL in Jurkat T cells. We found that inhibition of AMPK reduced transcriptional activation NF‐AT and AP‐1 in Jurkat T cells. Furthermore, we found that inhibition of AMPK blocked phosphorylation and activation of PKC‐theta, a critical molecule in T cell activation and FasL expression. Taken together, our results show that AMPK regulates T cell receptor‐induced FasL expression through activation of NF‐AT and AP‐1 pathways in Jurkat T cells and imply that AMPK may play a role in activation‐induced cell death during T cell activation.This work was supported by grants from KOSEF and KRF of Korea Government.
Role of ζ‐Crystallin and Other AUBPs in Bcl‐2 Over‐Expression Occurring in B‐cell CLLs
Authors: di Gesualdo Federico , Donnini Martino , Witort Ewa , Papucci Laura , Specogna Rebecca , Cianchi Fabio , Lulli Matteo , Capaccioli Sergio , Lapucci Andrea 
Published: June 2021

We previously identified in the 3'UTR of bcl‐2 mRNA an adenine + uracil‐rich element (ARE) thatregulates bcl‐2 expression at the post‐transcriptional level by interacting with specific AU‐BindingProteins (AUBPs). In most solid tumours and leukemias, bcl‐2 is overexpressed without any obvious gene rearrangement or mutation, suggesting that it could depend on impaired ARE/AUBP interaction based post‐transcriptional control. Investigating this possibility, we have recently disclosed a new bcl‐2 AUBP, ζ‐crystallin, which increased binding to the ARE of bcl‐2 mRNA resulted in bcl‐2 over‐expression in T‐cells of Acute Lymphocytic Leukemias (ALLs) patients as compared to T‐cells from healthy donors. Here, we also show that ζ‐crystallin and Bcl‐2 protein levels are strictly co‐related in B‐cell Chronic Lymphocytic Leukemias (CLLs) and demonstrate that this is consequent to bcl‐2 mRNA stabilization by ζ‐crystallin, in a circuit involving shifting of other bcl‐2 AUBPs. Our results clearly indicate that ζ‐crystallin overproduction contributes to bcl‐2 over‐expression and thus to the onset of human B‐cell CLLs.
Immortalization of human small airway epithelial cells with characteristics of bronchioalveolar stem cells
Authors: Gao Boning , Huang Chunxian , Sullivan James P , spinola Monica , Raso Maria Gabriela , Wistuba Ignacio , Shay Jerry , Minna John D 
Published: June 2021

Most of our current understanding of stem cells in the adult lung is based on mouse models while information in the human lung remains poorly defined. A major advance would be the ability to reproducibly grow human lung stem or progenitor cells to allow their systematic study and genetic manipulation. Toward this goal, we have worked out conditions to routinely immortalized (NB = 9) human small airway epithelial cells (HSAECs) from peripheral lung using Cdk4 and hTERT expression vectors in these cells. As an example strain HSAEC1 grows in serum free SAGM medium (Clonetics), forms colonies in liquid media efficiently, but does not form colonies in soft agar or tumors in SCID/NOD mice. HSAEC1 expresses lung basal/stem cell markers (aldehyde dehydrogenase, p63, Cytokeratin14 and 17, and is resistant to 1 mM naphthalene) but very low or undetectable Clara cell, Type1 and Type2 cell markers in SAGM, which are then expressed when grown in Matrigel culture or in serum. Finally, the cells can be genetically manipulated toward oncogenesis (with KRASV12, and or missense p53). We conclude, that we have prepared multiple, immortalized strains of human peripheral lung epithelial cells with many characteristics of lung stem or progenitor cells that are experimentally tractable for studying lung differentiation and tumorigenesis.This work is supported by NCI SPORE P50CA70907, and NASA/DOE NSCOR NNJ05HD36G, DE‐AI02‐05ER64068
Glybenclamide Exhibits Thromboxane Receptor‐Dependent Antiplatelet Effects
Authors: Ting Harold J , Khasawneh Fadi T 
Published: June 2021

BackgroundProper platelet function is vital as they are the main cellular agents of hemostasis. Conversely, inappropriate activation of platelets is featured in occlusive disease such myocardial infarction, and stroke. While the thromboxane A2 pathway of platelet activation has been identified as an attractive target for pharmacological intervention, no thromboxane receptor (TPR) antagonists are available for clinical use. Given the structural similarity between the antidiabetic sulfonylurea agent Glybenclamide (Glyb) and the TPR antagonist SQ29548, we hypothesize that Glyb exhibits antiplatelet effects via interaction with TPR.ObjectiveCharacterize the potential antiplatelet capacity of Glyb.MethodsIsolate platelets from healthy donors who denied taking medication in the last 10 days and then investigate the effects of Glyb on platelet aggregation induced by the TPR agonist U46619, the thromboxane A2 precursor arachidonic acid (AA), ADP, as well as the protease‐activated receptor peptide (PAR4) using optical aggregometry.ResultsGlyb was found to dose‐dependently inhibit U46619/AA‐ (i.e., TPR‐) mediated platelet aggregation, but had no detectable effects on that triggered by ADP or PAR4.ConclusionOur findings suggest a therapeutic role for Glyb in thrombotic diseases via blockade of TPRs, and may lay the foundation for the design of therapeutic agents for selective targeting of TPR.
A pilot study of paternal drug exposure: the Motherisk experience
Authors: Lee Candace Y.W. , Jin Cheng , Mata Andrea M. , Tanaka Toshihiro , Einarson Adrienne , Koren Gideon 
Published: June 2021

BackgroundThere is a dearth of information on medication safety and counseling experience regarding paternal exposure (PEx) to drugs and chemicals in the peri‐conception period. The Motherisk Program, first established in Toronto, ON, Canada in 1985, is a teratology information and clinical consultation service with a focus on drug safety during pregnancy. Here, we reviewed for the first time our counseling experience with PEx.MethodsThis is an observational retrospective cohort study using a prospectively collected database. Telephone counseling records from Jan 1, 2002 to Dec 31, 2006, inclusive, were screened manually for PEx.ResultsOf a total of 157,933 telephone requests for counseling over this 5‐year period, there were 249 (0.16%) requests for counseling on PEx. Most of these calls (177/249) were referred by health professionals. Counseling for exposure to drugs was requested in the majority of cases, with the remainder being exposure to chemicals, radiation, infection, or combinations of the above. The four drugs on which counseling was most frequently sought were methotrexate (33 requests), finasteride (24 requests), azathioprine (20 requests), and prednisone (18 requests). For many drugs, there was a paucity of information on PEx.ConclusionThere is an ongoing need for safety data on PEx. Future studies are needed to evaluate the safety of PEx to selected drugs in the peri‐conception period.HSC Research Institute (CYL,GK); equal contribution (CYL,CJ)
LIPIDS PROFILE IS THE MOST INFLUENTIAL CARDIOVASCULAR RISK FACTOR ON THE OXIDATIVE STRESS IN A GENERAL HUMAN POPULATION.
Authors: Cuevas Santiago , Roman Elena , Lopez Bernardo , Hernandez Isabel , Carbonell Luis F 
Published: June 2021

AimOxidative stress and inflammation appear to play an important role in the process of ageing and in the associated dysfunction of the human cardiovascular system. In this study we tried to identify which of the cardiovascular risk factors are better related with oxidative stress, in a human population with a wide range of age.MethodsThe study population included subjects (n=160; age range: 18‐84 years) living in the metropolitan area of Murcia (Spain). It were measured general blood biochemical variables, arterial blood pressure and anthropometrical data, as well as plasma concentration of the oxidative stress and inflammation markers, myeloperoxidase (MPO, EIA), C‐reactive protein ultrasensitive (hsCRP; EIA), and malondialdehyde (MDA; HPLC). It were also collected information about personal habits of the subjects (tabaquism, alcohol and diet). Interactions between variables were calculated by correlation (Pearson or Spearman) and multiple regression analyses.ResultsCRP, MPO and MDA were associated to trigliceryds and/or total cholesterol. Multiple regression tests indicated that body mass index was the most influential factor on the lipids variables.ConclusionTo higher blood concentration of triglycerides and total cholesterol more oxidative stress and inflammation in a general human population. Body mass index may be a good marker of this association.
Perturbation of Cell Cycle Progression by A G‐Quadruplex‐Specific Stabilizer
Authors: TSAI YUAN‐CHIN , Qi Haiyan , Lin Chao‐Pao , John Kerrigan , Rzuczek Suzanne , Rice Joseph E , LaVoie Edmond J , Pilch Daniel S , Liu Leroy F 
Published: June 2021

AbstractThe scarcity and difficulty in total synthesis of telomestatin have led to the development of a facile synthetic scheme, leading to the synthesis of structurally similar hexaoxazole‐containing macrocycles, among which HXDV has been shown to exhibit highly specific binding to human telomeric G‐quadruplexes in vitro through a capping mechanism.Here we study the mechanism of the anti‐proliferative activity of this novel G‐quadruplex stabilizer, HXDV. Surprisingly, HXDV was found to exhibit anti‐proliferative activity against many tumor cells independently of their telomerase status and induce strong apoptosis within 16 hrs of treatment. HXDV also inhibited the progression of the cell cycle, resulting in accumulation of cells at the G2/M phase of the cell cycle. Interestingly, our results showed that cells were arrested at the M, rather than G2, phase of the cell cycle. However, unlike tubulin inhibitors which also arrest cells at M phase, HXDV reduces the expression level of the key M phase regulator Aurora A kinase. In the aggregate, our results suggest that HXDV is a novel M phase blocker, with a possible mode of action distinct from tubulin inhibitors.
Phenotypic variation of mineral contents in beef
Authors: Duan Qing , Reecy James M. , Tait Richard JR , Schoonmaker Jon P. , Beitz Donald C. , van Eenennam Allison , Mateescu Raluca , Garmyn Andrea 
Published: June 2021

Humans have a daily minimal requirement for minerals, of which beef can be a major supply. However, it is unknown to what extent the contents of minerals vary in beef. Thus an objective of this study was to determine the extent of phenotypic variation of mineral contents in beef. Beef longissimus dorsi muscle samples were collected from 1086 head of purebred Angus cattle, trimmed off external connective and adipose tissue, and freeze ground before mineral assays. After microwave digestion, concentrations of iron, zinc, magnesium, phosphorus, potassium and sodium were measured by ICP‐OES. The mean values ± SE for the six minerals (based on wet weight) are 13.97 μg/g ± 0.09, 39.98 μg/g ± 0.35, 219.94 μg/g ± 0.94, 1772.14 μg/g ± 9.68, 3083.61 μg/g ± 21.35, and 434.77 μg/g ± 2.44, respectively. Nearly two‐fold concentration differences were observed between the upper 90% and the lower 10% in most minerals. Significant correlations between mineral contents were also found. The large mineral content variations in beef indicate that it may be possible to improve the nutrient contents of beef thereby making it even better source of nutrients.Research support: PFIZER INC. Animal Health Division and Affiliates
Effects of Changes of Diet from High‐fat to Low‐fat on Hepatic mRNA Levels of ACS, CPT‐1, and ACC
Authors: Shin Gina , Lee In seok , Choue Ryowon 
Published: June 2021

AimsThe purpose of this study was to investigate the effects of dietary changes from high‐fat diet (HFD, 45% of total calories from fat) to low‐fat diet (LFD, 10% of total calories from fat) on hepatic mRNA levels of acyl coenzyme A synthetase(ACS), carnitine palmitoyltransferase‐1(CPT‐1), and acetyl coenzyme A carboxylase(ACC) as well as on serum and hepatic lipids in mice.MethodsFive weeks‐old male C57BL/6 mice were fed high‐fat diet for 9 weeks then switched to a low‐fat diet or continued the high‐fat diet for 3 weeks. Body weight, serum and hepatic lipid levels were measured. Expressions of ACS, CPT‐1, and ACC mRNA were also analyzed.ResultsThe results showed that after the high‐fat diets were switched to low fat diets, body weight, epididymal and retroperitoneal fats were significantly reduced (p<0.05). The levels of serum and hepatic total cholesterol were not different between the two groups however, serum TG levels of high‐fat diet followed by low‐fat diet group were significantly lower than those of high‐fat diet group (p<0.05). Hepatic mRNA levels of CPT‐1 and ACC were higher significantly in the group of high‐fat diet followed by low‐fat diet (p<0.05) however mRNA levels of ACS were not different between the two groups.ConclusionsChanges in the composition of dietary fat from high to low decreased significantly body fats and the serum TGs. Furthermore, changes of dietary fat composition affected differently the hepatic mRNA levels of ACS, CPT‐1 and ACC.
Emerging science demonstrates that L‐theanine and caffeine in combination can help improve attention
Authors: Kovacs Eva M.R. , Balentine Douglas A. , Einöther Suzanne J.L. , Rycroft Jane A. , de Bruin Eveline A. 
Published: June 2021

Double‐blind randomized placebo‐controlled crossover studies have shown that consumption of L‐theanine combined with caffeine can help improve attention (1,2,3). Haskell et al. (1) observed that 250mg of L‐theanine and 150mg of caffeine improved aspects of cognition and mood, while either ingredient alone did not. Owen et al. (2) demonstrated that lower levels of L‐theanine (100mg) and caffeine (50mg) also improved aspects of attention and mood, while caffeine alone did not. Similarly, Kelly et al. (3) observed that 100mg of L‐theanine and 50mg of caffeine acted synergistically, improving behavioral aspects of attention as well as affecting alpha brain wave activity related to attention during task performance. In a recent double‐blind randomized crossover study, we confirmed previous findings, demonstrating improved selective attention with consumption of an iced tea beverage containing L‐theanine (97mg) and caffeine (40mg) relative to a placebo iced tea beverage (4). We conclude that there is emerging evidence showing that L‐theanine and caffeine, when consumed in combination and in amounts of 100mg of L‐theanine and 50mg of caffeine, can help improve attention.This research was supported by the Lipton Institute of Tea
Experimental Validation of a Model of the Arterial Circulation
Authors: Edwards Jonathan William , Rose William C. 
Published: June 2021

Accurate noninvasive measurement of the blood pressure waveforms throughout the body is clinically desirable, but difficult to accomplish. We used a computational model, based on a description of the architecture and mechanical properties of the arterial network and blood, to predict dynamic pressure throughout the arterial vasculature. Applanation tonometry was used to measure dynamic pressure noninvasively at the carotid, radial, and femoral arteries under different conditions. A pressure waveform from one recording site was used as input to the model. Model parameters were adjusted to obtain the best fit between the pressures predicted at other locations and the pressures actually measured at those locations. The site whose pressure was used as the input was altered, and the ability to accurately predict pressures at the other sites was compared.In ten healthy subjects, radial artery pressure allowed most accurate prediction of pressures elsewhere. Vascular stiffness, resistance, and the dependence of stiffness on arterial diameter were determined from the fitted model parameters. The model provides insight into the effects of physiological and pharmacological stimulation on arterial vascular properties in vivo. The model also provides a noninvasive estimate of central aortic pressure, which is valuable for understanding ventricular‐vascular coupling in health and disease.
Characterization of the mitochondrial isoform of FASTK
Authors: Jourdain Alexis , Koppen Mirko , Martinou Jean‐Claude 
Published: June 2021

The Fas‐Activated Serine/Threonine kinase (FASTK) is a protein that regulates alternative splicing in the nucleus (Simarro et al., 2007). This protein is also present in the cytosol where it is associated to stress granules and processing bodies (Kedersha et al., 2005). FASTK is the founding member of the FASTKD family, which contains five other proteins (1–5). These proteins localize to mitochondria (Simarro et al., 2009) and recently FASTKD2 has been reported to regulate cytochrome c oxidase activity (Ghezzi et al., 2008), whereas FASTKD3 is required for mitochondrial respiration. Importantly, FASTKD2 has been identified to be mutated in a case of mitochondrial encephalomyopathy.We have characterized the two different isoforms of FASTK and we have found that the isoform 1 of the protein contains an internal and atypical mitochondrial targeting signal. This isoform is in the mitochondrial inner membrane with its domains exposed to the matrix. Interestingly, we also found that in mitochondria FASTK is not equally distributed but is rather concentrated in particular foci within mitochondria. We are now investigating the function of FASTK in mitochondria, as well as of the FASTKDs.
An open‐label study to assess the efficacy of a dietary supplement in subjects who display subjective memory complaints
Authors: Hirsh Steven P. , Zhang Peter , Joyal Steven 
Published: June 2021

ObjectiveThis study assessed the change in cognitive performance from baseline to Day 60 based on an online cognitive assessment tool, results from a CGI‐I (Clinical Global Impression‐Improvement) Scale, and an assessment survey for consumer attitude.MethodsForty middle age to elderly subjects were enrolled and dosed with three capsules per day of the nutritional supplement. Cognitive evaluations were conducted at various time points. The results achieved yielded a cognitive score measuring different cognitive capabilities. The CGI‐I provided an overall clinician‐determined summary measure.ResultsTwenty‐nine subjects completed the study. There were no significant adverse events reported. Preliminary results revealed a statistically significant improvement (p<0.05) in the various tests including Working Memory‐N‐Back which displayed the most significant improvement. Based on the CGI‐I, improvement was noted after 60 days of product dosing.ConclusionThese preliminary results revealed beneficial effects on memory, higher‐order and complex cognitive processes. The results attained through the CGI Improvement Scale reflected an overall improvement in the subject following administration of the study product.Supported by: Life Extension Foundation Inc.
Protein intake and yoga influence whole body protein turnover in middle‐aged women
Authors: Colletto Megan , Rodriguez Jose , DelFavero Jeffrey , Rodriguez Nancy 
Published: June 2021

This study characterized effects of protein intake on whole body protein turnover (WBPTO) between middle‐aged (50–70 y) women who practice yoga (YOGA) and healthy sedentary controls (CON). WBPTO (15N glycine method) was determined at baseline (BASE) and following 2 wk of diet interventions (T2W) where protein intakes approximated the RDA (RDA; .8 g/kg) or 1.6 g/kg (HP). 15N ammonia enrichment was determined for an overnight urine collection at BASE and T2W. Protein and energy intakes were estimated from 7 d diet records. Data represent mean ± SE and level of significance was P<0.05. Age, weight and BMI were similar for YOGA (n=4, 54.8±1.4 y, 62.0±5.3 kg, BMI=24.4 ± .9) and CON (n=8, 54±1.5 y, 66.3± 2.6 kg, BMI = 25.6 ± .7). Q was lower for YOGA vs CON (Q: .62 ± .05 vs .75 ± .04) while PB (2.86 ± .29 vs 3.07 ± 47), PS (3.33 ± .33 vs 4.47 ± .52) did not differ. Q increased with HP for YOGA (61 ± .11 vs 1.1 ± .19) and CON (72 ± .03 vs 1.03±.10). The change (T2W‐BASE) in Q was greater for HP for YOGA (.48 ± .08 vs .04 ± .03) vs CON (.32 ± .08 vs ‐.30±.16). PS increased for HP for YOGA (3.14 ± .56 vs 5.29 ± .58) and CON (3.81 ± .18 vs 5.68 ± .62) from BASE to T2W. PB increased for CON – HP (2.79 ± .64 vs 5.88 ± 0.72). At T2W, PS was greater for HP for CON (5.68 ± .62 vs 3.74 ± .07). Increased consumption of protein affected WBPTO in middle‐aged women. Research is warranted to delineate the protein related metabolic response to protein intake in active and sedentary middle‐aged women.Grant Funding Source : Dairy Research Institute