bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenosine A1 receptors induce translocation of PKCε to the caveolar membrane of cardiac myocytes
Authors: Yang Zhaogang , Garg Vivek , Hu Keli
Published: June 2021

Caveolae are specialized microdomains of the plasma membrane. They play an important role in the cardioprotective effect of ischemic preconditioning. Both adenosine receptors and PKCε, which have been shown to reside in the caveolae of cardiac myocytes, are associated with ischemic preconditioning. However, the potential link between adenosine receptors and PKCε has not been elucidated. The present study was designed to test the hypothesis that adenosine A1 receptors induce the translocation of PKCε to the plasma membrane within caveolae. Immunoblot analysis from the homogenate of freshly isolated cardiac myocytes revealed that the intensity of 100 kD band corresponding to PKCε increased significantly in the membrane fractions in cells pretreated with adenosine (100 μM) when compared with non‐stimulated cells. The effect of adenosine on PKCε translocation was blocked by a specific A1 antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX, 1 μM). Western blot in caveolin‐enriched fractions prepared from isolated cardiac myocytes showed that immunoreactivity for PKCε increased significantly from cells treated with adenosine but not with adenosine plus DPCPX. Furthermore, PKCε was detected in the anti‐caveolin‐3 immunoprecipitates from caveolar fractions. In conclusion, we demonstrate that activation of adenosine A1 receptors promotes the translocation of PKCε to the caveolin‐enriched plasma membrane of cardiac myocytes.
Involvement of PARP‐1 in the Signal Transduction Pathway Between IL‐4 and IL‐5
Authors: Datta Rahul , Naura Amarjit , Boulares Hamid
Published: June 2021

Our lab focuses on the role of poly(ADP‐ribose)polymermase‐1(PARP‐1) in the pathogenesis of pulmonary inflammation. We have recently shown that PARP‐1 inhibition through genetic or pharmacological means in the OVA‐challenge mouse model of asthma results in a reduction in eosinophilia in comparison to mice with normal PARP‐1. Furthermore, there is a reduction in the inflammatory cytokines IL‐4 and IL‐5. We show the reduction in eosinophilia may be associated with an interruption in the IL‐4 receptor signal transduction pathway. The expression of GATA3, a critical transcription factor for IL‐5 expression is decreased in IL‐4 treated splenocytes derived from PARP‐1‐/‐ mice. Such an effect was associated with a decrease in the expression of STAT6, a transcription factor for GATA3. Such a decrease was not associated with a decrease in the pathway components JAK1 and JAK3. These findings suggest that PARP‐1 plays an important role in the expression of STAT6 and that the reduction of STAT6 expression in PARP‐1‐/‐ mice leads to a decrease in GATA3 expression in these mice. This may explain the reduction in IL‐5 production when PARP‐1 is inhibited in the OVA‐challenge mouse model.
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

Background

There 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.

Methods

This 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.

Results

Of 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.

Conclusion

There 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)
Formation of Nitroapocynin and Diapocynin in Reactions of Apocynin with Peroxynitrite/CO2: Implications for the use of Apocynin as a Selective Inhibitor of NADPH Oxidase System
Authors: Gernapudi Ramkishore , Babu Sainath , Raghavamenon Achuthan C , Uppu Rao M
Published: June 2021

Peroxynitrite (PN) is an elusive oxidant formed in biological systems from the reaction of nitric oxide (•NO) with superoxide (O2•–). In bicarbonate‐rich physiological fluids, PN reacts predominantly with CO2 forming nitrogen dioxide (•NO2) and carbonate radicals (CO3 •–) in yields up to 40 mol% which, in turn, react with target molecules. In the present study, we examined the reactions of PN/CO2 with apocynin (Apo), a classical inhibitor of NADPH oxidase system with potential for treating inflammatory and degenerative conditions. At pH 7.2, Apo readily reacted in PN/CO2 system with an over all yield of oxidation of 36 ± 2 mol% (based on the initial concentration of PN employed). About 85% of the oxidation of Apo could be accounted for by the formation nitroapocynin (NitroApo; 5.4 ± 0.2 mol%) and diapocynin (DiApo; 12.8 ± 0.7 mol%). When pH was varied between 5.76 and 8.34, the yield of NitroApo increased until pH 6.74 and then tended to decline. The yield of DiApo, on the other hand, decreased with increase in the pH. At a given pH, the yield of NitroApo but not DiApo decreased with increase in the concentration of Apo. These results are consistent with the reactions of CO3▸ and •NO2 with the phenol and phenolate forms of Apo and their 1‐electron oxidation product, Apo phenolate radical. The implications of Apo reaction in the PN/CO2 system will be discussed in relation to the specificity of Apo as a probe for NADPH oxidase system and the possible metabolism of xenobitics in general by ▸NO‐derived oxidants.
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

Aim

Oxidative 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.

Methods

The 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.

Results

CRP, 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.

Conclusion

To 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

The 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.
Zinc as an Alternative Signal to Calcium
Authors: Rink Lothar , Haase Hajo
Published: June 2021

Cytosolic alterations of calcium ion concentrations are an integral part of signal transduction. Similar functions have been hypothesized for other metal ions, in particular zinc (Zn2+), but this still awaits experimental verification. Zn2+ is important for multiple cellular functions, especially in the immune system. Here we show that an increase of intracellular zinc ion concentration could be observed after specific cell stimulation by lipopolysaccharide, phorbolester, cytokines and other stimulants in T cells, monocytes, HEK cells and other cell types. However, an increase of the intracellular zinc ion concentration is not observed after every cell activation, but is stimulant‐dependent and alternative to calcium. For example, the phorbolester PMA induced an increase in intracellular zinc in Jurkat T cells, whereas the lectin phytohemagglutinin induced an increase in calcium. Furthermore, calcium and zinc signals are completely independent since the mercury‐induced zinc release still happens after exhaustion of intracellular calcium stores. In conclusion this function of Zn2+ is not limited to cells of the immune system, but seems to be another generalized signalling system based on intracellular fluctuations of metal ion concentration, acting parallel to Ca2+. This generalized role of zinc may explain the multiple effects observed in zinc deficiency.
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

Aims

The 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.

Methods

Five 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.

Results

The 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.

Conclusions

Changes 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.
The Effect of C‐Reactive Protein on Glucose Release in Primary Hepatocytes
Authors: Ellis Flannery , Pfaffenbach Kyle , Wang Dong , Wei Yuren , Pagliassotti Michael
Published: June 2021

C‐reactive protein (CRP) is associated with increased risk of cardiovascular disease and can reduce insulin signaling in skeletal muscle cells. The aim of this study was to determine whether CRP impairs glucose release in primary hepatocytes. Hepatocytes were isolated from male Wistar rats (n=3) by collagenase perfusion. Primary hepatocytes were provided glucose‐free media containing 10 mM lactate, 1 mM pyruvate 0, 1 or 10 nM insulin, and 0 or 10 μg/ml CRP for 6h. Media samples were analyzed for glucose concentration and cells harvested for total protein analysis. In the absence of insulin, glucose release was not different in the absence or presence of CRP. In the presence of 1 nM insulin, CRP increased glucose release (μmol/mg protein/6h) by ~25% (14.0±1.7 vs. 11.3±1.7; mean±SD). In the presence of 10 nM insulin, CRP increased glucose release by only ~8% (13.0±2.3 vs. 12.0±0.4). This data suggests that CRP may reduce the ability of insulin to suppress glucose release in primary hepatocytes.
Isoflavone concentration of soy infant formula influences adipose gene expression in the neonatal piglet
Authors: Schantz Brooke Blue , Cooke Paul S. , Donovan Sharon M.
Published: June 2021

Soy isoflavones (ISO) affect adipocyte development in rodents. Currently, 25% of formula‐fed infants receive soy formulas (SF) that contain 25 mg/L aglycone ISO. Herein, the hypothesis that ISO influenced adipose development was tested. Piglets (n=74) were fed cow milk‐based formula (CMF), SF (25 mg aglycone ISO/L) or a low ISO SF (LSF; 1.1 mg aglycone ISO/L). Subcutaneous (SC) and renal adipose were collected on d 2, 7, 12 and 21. SC adipocyte number and size were measured using a Coulter Counter and gene expression was assessed by Real‐Time PCR. Weight gain was similar in all groups. Adipocyte cell size increased between d 7 and 21 (p<0.02), but no effect of diet on adipocyte number or size was observed. Diet modulated gene expression in a tissue‐specific manner. In SC adipose, PPAR‐γ expression was unaffected by diet, C/EBP‐α was higher in SF than LSF and CM, and C/EBP‐β and lipoprotein lipase (LPL) were greater (p<0.05) in SF than CM, with LSF being intermediate and not different from either. In renal adipose, C/EBP‐α was unaffected by diet, PPAR‐γ and LPL were higher in LSF than CM with SF being intermediate and not different from either, and C/EBP‐β was greater (p<0.05) in SF than CM with LSF intermediate and not different from either. Thus, compared to CMF, SF induced expression profiles consistent with adipocyte differentiation, but SF and ISO effects differed between SC and renal adipose. (Solae LLC and IL Soy Association)
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
Effects of the Curves® fitness & weight loss program in women with medically managed conditions: training adaptations
Authors: Byrd M , Ferreira M , Li R , Parker A , Galbreath M , Jitomir J , Serra M , Beavers K , Dove J , Culbertson J , Hudson G , Shelmadine B , Curts C , Moreillon J , Deike E , Rasmussen C , Kreider R
Published: June 2021

146 sedentary women (50±10 yrs, 162±6 cm; 95±20 kg; 46±5% body fat, 36±7 kg/m2) with medically‐managed conditions were assigned to an exercise & no diet group (E) or a low calorie high carbohydrate (HC) or high protein (HP) diet. Diets consisted of 1,200 kcal/d for 1‐wk and 1,600 kcal/d for 9 wks of either HC (55% C, 15% P, 30% F) or HP (15% C, 55% P, 30% F). During weeks 10‐14, subjects consumed a HC maintenance diet (2,600 kcals/d) and were instructed to diet for 2‐d at 1,200 kcals/d if they gain 3 lbs. Subjects participated in a supervised Curves fitness program 3‐d per wk. Fitness and health measurements were obtained at 0, 10 and 14 weeks. Data are presented as means ± SD changes from baseline. Training significantly increased (p<0.05) 1RM bench press (15±22%), 1RM leg press (23±29%), BP lifting volume (37±55%), LP lifting volume (23±29%), and relative peak oxygen uptake (7.4±19%) while decreasing waist circumference (‐3.2±5%), hip circumference (‐2.8±4%), resting HR (‐3.0±15%), total CHL (‐1.4±16%), and LDL (‐2.8±18%). No significant differences (p>0.05) were observed in changes in resting SBP (‐0.8±13%), DBP (‐0.7±14%), glucose (0.1±19%), triglycerides (0.8±34%), or HDL (‐0.1±20%). Results indicate that the Curves program improves selected markers of health and fitness in women with medically‐managed conditions.
Healthy People Nutrition and Overweight Objectives
Authors: Kim Insun
Published: June 2021

Healthy People is a comprehensive health promotion and disease prevention agenda for the United States. The goal of The Healthy People 2010 Nutrition and Overweight objectives is to promote health and reduce chronic disease associated with diet and body weight. For the next decade, Healthy People 2020 envisions a society in which all people live long, healthy lives. Toward that end, Healthy People 2020 will i) identify nationwide health improvement priorities; ii) increase public awareness and understanding of the determinants of health, disease, and disability and the opportunities for progress; iii) provide measurable objectives and goals that can be used at the national, state, and local levels; iv) engage multiple sectors to take actions to strengthen policies and improve practices that are driven by the best available evidence and knowledge; and v) identify critical research and data collection needs. Nutrition is likely to play an even more prominent role in Healthy People 2020 as it focuses on upstream determinants of health. This paper will discuss progress made in the nutrition and overweight objectives toward the year 2010 and identify disparities among population subgroups. It will also present important information for the nutrition research community to get engaged in the development of nutrition and overweight objectives for the year 2020.
Exercise modifies microvascular reactivity to insulin in the OLETF rat, a rodent model of hyperphagia‐induced obesity and type II diabetes
Authors: Mikus Catherine R. , Rector R. Scott , Thorne Pamela K. , Morris E. Matthew , Booth Frank W. , Ibdah Jamal A. , Laughlin M. Harold , Thyfault John P.
Published: June 2021

The purpose of this study was to determine whether chronic voluntary wheel running (RUN) prevents impairments in insulin‐stimulated vasodilation (ISD) associated with obesity and type 2 diabetes (T2D) independent of the effects of RUN on adiposity. We randomized Otsuka Long Evans Tokushima Fatty (OLETF) rats, a model of hyperphagia‐induced obesity and T2D, to: 1) RUN, 2) caloric restriction (CR), or 3) sedentary (SED) groups (n=6‐8/group) at 4 wks of age. At 40 wks, body weights of RUN and CR were similar, and both were lower than SED (520±22, 503±12, 648±31 g, respectively; P<0.05). Fasting blood glucose and glucose area under the curve (AUC) following an intraperitoneal glucose tolerance test were higher in SED than CR or RUN (54651±2309, 45792±4267, 37891±4647 mg/dL*120; P<0.05) and greater in CR than RUN (P<0.05). ISD in second‐order arterioles isolated from gastrocnemius muscle (recruited in RUN) was greater in RUN than CR or SED at insulin doses = 10 μIU/mL (66±17, 17±9, 11±7 % change from baseline; P<0.05) but did not differ between SED and CR. These effects were ablated in the presence of an endothelial nitric oxide (NO) synthase inhibitor, suggesting enhanced ISD in response to chronic exercise is NO‐mediated and independent of attenuating excess adiposity. Funding: MU Department of Internal Medicine, MU Institute for Clinical & Translational Sciences, NIH HL36088 (MHL).
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.
Recurrence quantification analysis (RQA) used for detection of ST segment deviation
Authors: Wilkins Brek A. , Komanduri Ranga , Bukkapatnam Satish , Yang Hui , Warta Greta , Benjamin Bruce A
Published: June 2021

The current clinical gold standard for the detection of acute myocardial ischemia is ST segment deviation from baseline. Unfortunately, ST segment deviation as a marker for ischemia has well documented limitations. Recent studies have used RQA to quantitatively analyze changes in heart rate variability. The purpose of this study is to use nonlinear dynamical approaches, RQA, to test the hypothesis that R‐R beat patterns are different in ischemia compared to control states. RR intervals were analyzed from 24hr ECG recordings of transient myocardial ischemia patients from PhysioNet's Long‐term ST database. The CRP Toolbox was used for RQA computation. RQA parameters included: embedding dimension=4, time delay=4, window size=500, and radius .8. All RQA statistics for ischemic patients were compared to healthy controls, supine and tilt. Results show that %recurrence (2±1 vs. 15±5, mean±SD), %determinism (0.5±0.28 vs. 0.95±0.04), and entropy (1.04±0.69 vs. 2.61±0.55, mean±SD) are significantly elevated in ischemia patients during ST deviation compared to healthy controls. Furthermore, these same RQA statistics reveal significant differences between ischemia with ST segment elevation and ~1.5hrs pre‐ischemia. This study suggests that RQA can be used to detect ischemia without the use of the current clinical gold standard ST deviation.
Maturation of the oxygen‐induced contractile response of the chicken ductus arteriosus during exposure to increased oxygen
Authors: Dzialowski Edward M , Greyner Henry
Published: June 2021

As with the mammalian DA, the avian ductus arteriosi (DA) are O2‐sensitive vessels that constrict in response to increasing O2 levels. The O2‐induced contraction of the avian DA is strongest during the last stages of hatching on day 20 of incubation. Previously we have shown that on day 19, the chicken DA respond weakly to acute increases in O2. Here we examined the O2‐induced contractile response of the chicken DA during a longer three hour exposure to 25 kPa O2 on day 19 of incubation. The DA initially responded to the increase in O2 with a weak contraction (0.15 ± 0.04 mN/mm) that increased in strength (0.63 ± 0.06 mN/mm) during the three hour exposure to 25 kPa O2. A tonic influence of nitric oxide appeared during the three hour exposure to 25 kPa O2. The contractile response after three hour exposure to O2 was not mimicked by the Kv channel inhibitor 4‐aminopyridine. This O2‐induced contraction is mediated by both L‐type Ca2+ channels and internal Ca2+ stores. The Rho‐kinase pathway inhibitors Y‐27632 and fasudil produced significant relaxation suggesting a role for Ca2+ sensitization in the contractile response to the three hours of elevated O2. While the day 19 DA initially exhibits an immature contractile response to O2, the maturation of the pathways regulating O2‐induced contraction were accelerated by longer exposure to 25 kPa O2 producing contractions similar in magnitude to those found during the last stage of hatching.
The production of exo‐β‐glucosidases from Penicillium spinulosum chemostat and liquid shake cultures
Authors: Wheeler Timothy W , Deffit Sarah N , Kochen Michael A , Anderson Ryan T , Bonetti Sandra J
Published: June 2021

The objectives of this project were to: (1) determine optimal conditions for production of exo‐β‐glucosidases or cellulases in both chemostat and flask cultures of Penicillium and (2) isolate and characterize this activity from P. spinulosum. In P. spinulosum chemostat cultures, strains were selected by using cellulose as the sole carbon source and the resulting strains produced a fourfold increase in enzyme. In liquid shake cultures, trials were performed to optimize enzyme production by P. spinulosum in cultures grown on either glucose‐ or galactose‐containing standard growth media (Glc‐ or Gal‐SGM). Glc‐SGM was selected for enzyme production because cellulase activity peaked on days 12 and 13, remained consistently higher and contained fewer contaminating activities than in Gal‐SGM. Cellulase was purified from 13‐day Glc‐SGM culture filtrates by successive DEAE anion exchange and Sephacryl S‐300 size exclusion chromatographies. SDS‐PAGE was performed on isolated cellulase fractions to resolve a primary (~ 100 kDa) protein band for sequencing. The isolated cellulase was free of contaminating glycohydrolase activities. Research support provided by the Merck Institute for Science Education.
The effect of consuming biofortified beans on the iron status of Mexican school children
Authors: Haas Jere Douglas , Villalpando Salvador , Beebe Stephen , Glahn Raymond , Shamah Tere , Boy Erick
Published: June 2021

Advances in plant breeding have resulted in a 73% increase in the iron content of black bean varieties similar to those consumed in Mexico. The efficacy of consuming these biofortified beans was tested in 587 primary school children in the Mexican state of Oaxaca. We randomized 20 schools to consume either biofortified (95mg/kg Fe) or control beans (55mg/kg Fe) for 110 days. At baseline 137 children (24%) were iron depleted with serum ferritin <20μg/L, and 18% were anemic (Hb<110g/L). Children consumed an average of 11 kg beans during the trial and the high iron bean group consumed an estimated additional 18% of their RI for iron. Children in the high iron bean group had significantly greater reduction in transferrin receptor (TfR) from baseline to end line compared to the low iron group (p<.001). The more iron deficient subjects (high baseline TfR) experience the greatest group difference in change of TfR (p=.05) compared to subjects with lower baseline TfR (interaction of baseline TfR by bean group, p=.011). The greatest group difference in improvement in TfR was also seen in children who consumed the most beans throughout the feeding trial. Interpretation of change in ferritin values appears to be complicated by differential rates of infections in the 2 groups. We conclude that consuming beans that are bred for enhanced iron content improves selected measures of iron status in school children. Supported by HarvestPlus
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

Objective

This 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.

Methods

Forty 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.

Results

Twenty‐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.

Conclusion

These 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.
Plasma nutrient biomarkers of dietary intake in postmenopausal women with and without coronary heart disease (CHD): Insights from the Women's Health Initiative Observational Study (WHI‐OS)
Authors: Matthan Nirupa Rachel , Ooi Esther M , Booth Sarah L , Van Horn Linda , Neuhouser Marian L , Lichtenstein Alice H
Published: June 2021

The study aim was to quantify plasma nutrient biomarkers in WHI‐OS participants; cases with confirmed CHD (N=1214) and controls (N=1214) matched for age, enrollment date, race/ethnicity, and absence of CHD at baseline. Plasma phylloquinone, dihydrophylloquinone (dhK) and phospholipid (PL) fatty acid profiles were measured using HPLC and GC, respectively. Compared to controls, cases had higher plasma dhK and PL SFA; and lower PL eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels (all P<0.05). No significant differences were observed in plasma phylloquinone, PL MUFA, PUFA, omega‐6 or trans fatty acid levels. In multivariate conditional logistic regression analyses controlling for BMI, systolic blood pressure, smoking, education, medication/hormone use, family history of CVD/diabetes and leisure physical activity ‐ plasma dhK (2.2 [1.0–4.7]) and PL SFA (1.2 [1.1–1.3]) were associated with higher CHD risk, whereas EPA (0.7 [0.6–0.9]) and DHA (0.6 [0.4–0.8]) were associated with lower CHD risk (values are odds ratio [95%CI]; all P<0.01). These data suggest that plasma dhK and PL omega‐3 fatty acid levels, nutrient biomarkers indicative of partially hydrogenated fat and fish intake respectively, are independent predictors of CHD risk in this population. (NIH‐HHSN268200764317, ADB contract #: N01‐WH‐74317).
Contribution of food categories to energy intake of the U.S. population: What We Eat In America, NHANES 2007–2008
Authors: Hoy M. Katherine , Clemens John , Rhodes Donna G. , Moshfegh Alanna J.
Published: June 2021

To describe the contribution of different foods to energy intake (EI) of the U.S. population, 1‐day food intakes from What We Eat in America (WWEIA), NHANES 2007–2008 were analyzed using WWEIA Food Categories. These include 8 major categories and 33 subcategories. Intakes for the population 2 years and older, excluding breastfed infants (N= 8529) were included. On the reporting day, the contribution of major food categories (percent ± SE) to EI was: Dairy (11±0.3 %); Protein Foods (16±0.4%); Mixed Dishes (20±0.5%); Grains (25±0.4%); Beverages (13±0.3%); Fruits and Vegetables (8±0.2%); Other Foods (7±0.2%); Water (0). There were slight differences between males and females, 20+ years in percent contribution to EI from different food categories. For example, for males vs. females, Dairy contributed 9±0.3 vs. 11±0.5% and Protein Foods contributed 18±0.4% vs. 15±0.5%. Dairy contributed a higher percentage to EI of children 2–5 years (21±1%) compared with those 6–11 years (17±0.5%) and 12–19 years (11±0.8%). This data can inform monitoring of trends in dietary patterns of the U.S. population. Funding source: ARS, USDA.
Non‐Diet Soda Intake Independent of Weight Status Is Associated with Asthma among U.S. Adolescents
Authors: Park Sohyun , Blanck Heidi M. , Sherry Bettylou , Jones Sherry Everett , Pan Liping
Published: June 2021

Limited research shows an inconclusive association between soda intake and asthma, potentially attributable to certain preservatives in sodas. This national study examined association between current asthma and non‐diet soda intake among U.S. high school students. Analysis was based on the 2009 Youth Risk Behavior Survey and included 15,960 students in grades 9–12 with data for both non‐diet soda intake and current asthma status. The main outcome measure was current asthma (had been told by doctor/nurse that they had asthma and still have asthma). The exposure variable was drinking a can/bottle/glass of non‐diet soda during the past 7 days. A multivariable logistic regression model was used to estimate odds ratios (ORs) for non‐diet soda intake with current asthma after controlling for age, sex, race/ethnicity, weight status, and current cigarette use. Overall, 10.8% of students had current asthma. Furthermore, 12.9% of students who drank non‐diet soda ≥1 time/day had current asthma. Odds of having current asthma was significantly higher among students who drank non‐diet soda 2 times/day (OR=1.28) and ≥3 times/day (OR=1.64) compared with those who did not drink non‐diet soda after controlling for other factors. Efforts to reduce non‐diet soda intake among youth may have benefits beyond diet quality. However, the association of high non‐diet soda intake with current asthma needs to be examined longitudinally.
Views of the dynamic human spliceosome
Authors: Jurica Melissa S.
Published: June 2021

The spliceosome is the cellular machinery responsible for removing introns from gene transcripts and ligating together exons to form mature messenger RNAs. It therefore serves as a critical player in regulating human gene expression and proteome complexity. We are working to provide a structural framework to understand the molecular mechanisms of the spliceosome. This task is challenged by size and dynamics of the complex as it forms from over 100 components into several assembly intermediates and functional states. Using an in vitro splicing system in human cell extracts in which we modify the pre‐mRNA substrate upon which the complex is assembled, we have new made advances in capturing the spliceosome at distinct intermediate states relative to spliceosome chemistry. Mass spectrometry analyses of the proteins in the different spliceosome intermediate complexes indicate changes in composition, which we then relate to differences in the structure of the complexes that we observe by electron microscopy. Using a combination of crosslinking, chemical modification and mass spectrometry strategies, we have also identified proteins that change in their association with the RNA substrate as the splicing reaction is catalyzed. Taken together, these observations are building a picture of the molecular rearrangements that occur in the spliceosome during the transition between first and second step chemistry.
The regularity of breakfast could drive teenagers to consume more fruits and vegetables
Authors: Shin Dongsoon , Lee Seo-Mi
Published: June 2021

Recently epidemic prevalence of obesity is a worldwide phenomenon and this trend induces much interests on the consumption pattern of plants which are dietary sources of fiber, vitamins and phytochemical in their eating environments. This study was conducted to identify fruits and vegetables intakes of teenagers according to regularity of breakfast. The subjects are total 354 middle school students(166 boys and 188 girls, average age 15 yrs old) in Changwon city located in the south area of Korea. The regular breakfast affected significantly teenagersˈ consumption of the friuts and vegetables(p<.001). The 57.9% of subjects skipped frequently breakfast for lack of time or appetite. They enjoyed a snack once or twice a day such as bread, noodles such as ramyeun, while those having breakfast regularly consumed friut or milk products. And also they frequently consumed korean cabbage and tomato. However there were no significant differences in most nutrient intakes according to regularity of eating breakfast. Interestingly the higher nutritional knowledge scores were, the better eating habits were. Therefore nutritional education on regularity of eating breakfat could drive teenagers to consume more fruits and vegetables and less cookies and fastfoods.
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
Determination of glutamate requirement in growing rats by indicator amino acid oxidation
Authors: Sakai Ryosei , Kuwahara Tomomi , Kawamata Yasuko , Uneyama Hisayuki , Torii Kunio , Nakamura Hidehiro
Published: June 2021

Although many studies have investigated requirements for essential amino acids both in animals and human, few have done for non‐essential amino acids (NEAAs). This study aimed to determine requirement for glutamate (Glu), the most abundant NEAA in food proteins, in growing rats by the indicator amino acid oxidation (IAAO) method.

Wistar strain male rats (6wks old) were given fixed amount of diets containing varied doses of amino acid (AA) mixture with NRC 1995 composition (56–214 g/kg) hourly. Dietary labeling with an indicator AA ([1‐13C]leucine) started at 3h of feeding period and 13C‐enrichments of breath CO2 were monitored. Relation between dietary AA contents and IAAO (= average 13C‐enrichments from 4 to 7h) was analyzed to determine a breakpoint as its requirement. Similarly, relation between dietary Glu content and IAAO was analyzed in rats fed diets containing graded doses of Glu (0–100 g/kg).

In both experiments, increase of AA or Glu contents at lower doses reduced IAAO, but did not further at higher doses. Apparent breakpoints were determined in their biphasic relations, indicating 173 and 45 g/kg diet of requirements for AA and Glu, respectively. Glu requirement estimated in this study was almost identical with the value determined by nitrogen‐balance study. These results indicated the existence of Glu requirement and suggested importance of dietary Glu as one of components of protein nutrition.
A high protein diet upregulates whole‐body protein turnover during energy deficit
Authors: Margolis Lee M. , Cao Jay J. , Sauter Edward R. , Whigham Leah D. , McClung James P. , Combs Gerald F. , Young Andrew J. , Pasiakos Stefan M.
Published: June 2021

The effects of dietary protein level on whole‐body protein turnover (WBPTO) during energy deficit (ED) are not well described. Using a randomized‐block design, 24 males and five females (21 ± 3 yr) participated in a controlled trial. Volunteers consumed either standard (SP; 0.8 g·kg−1·d−1), moderate (MP; 1.6 g·kg−1·d−1), or high (HP; 2.4 g·kg−1·d−1) protein diets for 31 days. A weight maintenance (WM, days 1–10) period was followed by 21 days of ED (days 11–31), during which energy intake was restricted to 60% of total daily energy expenditure. Whole‐body protein breakdown, synthesis, and oxidation were determined at rest during WM (day 10) and ED (day 31) using primed, continuous [13C]‐leucine infusions. Volunteers lost (P < 0.05) 3.3 ± 0.9 kg body mass in response to ED regardless of dietary protein level. Protein breakdown decreased (P < 0.05) in response to ED for SP and MP diets, but did not change for HP. Synthesis decreased (P < 0.05) following ED regardless of dietary protein level. Protein oxidation (μmol·kg−1·h−1) increased linearly between SP (9.7 ± 0.5), MP (11.8 ± 0.5), and HP (13.9 ± 0.5) diets during WM, with increased oxidation observed only for HP (16 ± 0.7) during ED (diet‐by‐energy interaction, P < 0.05). These data demonstrate that the level of dietary protein intake modulates WBPTO during sustained ED, as consumption of a high protein diet upregulates WBPTO during ED.
SECIS‐ and UGA position‐dependent incorporation of selenocysteine into mammalian selenoproteins
Authors: Turanov Anton A , Hatfield Dolph L , Gladyshev Vadim N
Published: June 2021

Incorporation of selenocysteine (Sec) into selenoproteins (SPs) occurs in response to UGA that is recoded from its normal termination function. This process requires a specific structure in the 3′‐UTR of SP mRNAs, a SECIS element. We previously found that UGA codes for both Sec and Cys in Euplotes crassus and that Sec insertion is dependent on the position of UGA within the ORF. Herein, we report that the position of UGA within human TR1 (hTR1) mRNA is also important for efficient Sec insertion. Conversely, Sec was inserted at any placement of UGA within hTR3. Replacement of the 3′‐UTR of hTR3 with the corresponding segment of Euplotes TR2 restricted Sec insertion at the C‐terminal protein portion, similar to Sec insertion in Euplotes. Replacement of the 3′‐UTR of Euplotes TR2 with the 3′‐UTR from hTR3 changed the UGA coding function of eTR2, leading to insertion of Sec at previously restricted positions. Similar results were observed when only the SECIS elements were switched preserving the rest of the 3′‐UTRs. Mutations in hTR3 SECIS changed the UGA coding function, whereas mutations in the 3′‐UTR had little or no effect. The data indicate a key role of SECIS in UGA position‐dependent Sec insertion into mammalian SPs.