bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Hypercapnia and Skin Temperature on Pulmonary Ventilation in Hyperthermic Humans
Authors: Greiner Jesse G , Walsh Michael L , White Matthew D 
Published: June 2021

Hyperthermia potentiates the influence of CO2 on pulmonary ventilation (VE). It remains to be resolved how mean skin (TSK) and core temperatures contribute to elevated exercise ventilation response to CO2.PURPOSETo assess influences of TSK and end‐tidal CO2 (PETCO2) on the ventilatory equivalent for oxygen (VE/VO2) during exercise with a hyperthermic rectal temperature (TRE).HYPOTHESISDuring hyperthermia mean skin temperature will positively interact with PETCO2 in their influence on exercise ventilation.METHODSSix participants 1.78 ± 0.13 m (mean ± SD) in height, who weighed 74.7 ± 16.5 kg and were 24.3 ± 2.3 yrs of age performed three 1 h exercise trials on each of 2 days in a climatic chamber. For each exercise session conditions were maintained at an RH of 29.5 ± 8.9 % and ambient temperatures of one of 25, 30, or 35°C. This gave 3 significantly different TSK levels (F=15.8, p=0.001) between ~33 and ~36°C. In each trial the volunteer breathed eucapnic air for 5 min during rest before cycling on an ergometer at either ~50 W (normothermic TRE) or at ~150 W (hyperthermic TRE). Once TRE stabilized the volunteers breathed hypercapnic air twice for ~5 min with PETCO2 elevated to ~+4 and ~+8 mmHg.RESULTSIn the normothermic TRE condition there was a significant effect of PETCO2 (P<0.05) but no effect of TSK on ventilation. In the hyperthermic TRE condition for VE/VO2 there were main effects of TSK (F=4.0, p=0.06) and PETCO2 (F=13.2, p<0.0001) as well as a significant positive interaction (F=3.7, p=0.01) between TSK and PETCO2.CONCLUSIONDuring exercise with a steady state hyperthermic core temperature, skin temperatures and PETCO2 positively interact in their influence on exercise ventilation.Supported by NSERC, Canadian Foundation for Innovation.
Impaired coronary artery vasodilation during skin surface cooling in healthy older adults
Authors: Gao Zhaohui , Wilson Thad E. , Hess Kari L. , Monahan Kevin D. 
Published: June 2021

Cardiovascular‐related mortality increases in the cold winter months, particularly in older adults. To determine whether coronary artery blood flow responses to skin surface cooling differ with age, we studied 9 young (25±1 yrs) and 10 older healthy adults (65±2 yrs). We hypothesized that left anterior descending coronary artery blood velocity (CBV) responses, measured using Doppler transthoracic echocardiography, to skin surface cooling (15–18° C water perfused suit for 20 min) would be impaired with age. We found that cooling increased left ventricular wall stress, a determinant of myocardial oxygen consumption, in young (185.6±6.5 to 202.9 ±10.4 mmHg, P < 0.05) and older adults (189.1±8.8 vs. 222.7±14.7 mmHg, P < 0.01) although the magnitude of this response was twofold greater in older adults (Δ9.13±3.48% vs. Δ17.62±3.24%, young and older, respectively; P=0.09). Despite increased left ventricular wall stress during cooling in young and older adults CBV increased only in the young (20.86±1.32 to 25.56±1.24 cm/s, p<0.01) and not older group (17.60±1.09 to 19.93 ±0.97 cm/s, p=0.11). These data suggest that an impaired coronary vasodilator response to cold stress may contribute to age‐dependent increases in cardiovascular‐related mortality during the winter months in healthy adults.Support: NIH HL92309, AG24420 and M01 RR10732
Electrical stimulation of the subfornical organ induces feeding and drinking in satiated rats
Authors: Smith Pauline M , Ferguson Alastair V 
Published: June 2021

The subfornical organ (SFO), a circumventricular structure which lacks the normal blood brain barrier has been shown to play a key role in body fluid homeostasis. A role for the SFO in sensing circulating satiety signals has been suggested by electrophysiological studies demonstrating that anorexigenic (leptin and amylin) and orexigenic (ghrelin) satiety signals influence the excitability of separate populations of SFO neurons. The present study examined whether electrical stimulation of the SFO influenced feeding in satiated rats.Male Sprague Dawley rats implanted with concentric bipolar SFO stimulating electrodes received 5 min electrical (100 or 200μA) or sham stimulation and food and water intake measured. Once animals had undergone both electrical and sham stimulation protocols the brain was removed to confirm the location of the stimulating electrode.SFO stimulation (100μA) elicited drinking in 5/6 animals tested (latency to drink: 6.2±2.6 min) but did not elicit eating. Higher stimulation intensities (200μA) elicited eating in all animals tested (food consumption: 0.6 ± 0.12g/100g body weight, n=6) with a mean latency to eat of 8.0 ± 4.0 min and elicited drinking in 5/6 animals (latency to drink: 15.2±2.6 min.) Sham SFO stimulation or stimulation (200μA) in non‐SFO sites (n=6) did not elicit feeding or drinking.The results of the present study showing that SFO stimulation induces feeding in satiated rats, lends support for a role for the SFO as an integrator of circulating peptides that regulate feeding. Supported by Canadian Institutes of Health Research
Disruption of the tight junction complex (TJ) by the cins‐mutation of NOD2
Authors: Poritz Lisa S , Harris Leonard R 
Published: June 2021

A mutation in the NOD2 gene is associated with Crohn's disease (CD). Patients with CD also have increased intestinal permeability and a defect in the TJ. The hypothesis for this study is that mutations in NOD2 disrupt the TJ.MethodsIEC‐18 cells (IEC‐18p) were stably transfected with human wild‐type NOD2 (IEC‐18w) or the c‐ins mutation (IEC‐18m). Monolayers were assayed for permeability and for TJ proteins (ZO‐1, 2, occludin, claudin‐1, 2, 4) by Western blot (WB), immunofluorescence, and qRT‐PCR.ResultsNOD2 was detected by WB only in IEC‐18w cells. By qRT‐PCR expression of NOD2 was < 1 (relative to GAPDH) in IEC‐18p, 10 in IEC‐18m, and >200 in IEC‐18w. The NOD2 protein was functional only in IEC‐18w and when stimulated upregulated NF‐κB. ZO‐1 was decreased in IEC‐18m and markedly disrupted (fig). In IEC‐18w cells ZO‐1 was unchanged from IEC‐18p. Claudin‐1 was significantly increased in IEC‐18w by WB and >600 fold by qRT‐PCR compared to IEC‐18p and IEC‐18m (p<0.01). ZO‐1, ZO‐2 and occludin were significantly decreased by qRT‐PCR in IEC‐18m compared to IEC‐18p and IEC‐18w, p<0.01. Permeability to RITC 70,000 was increased >150% in IEC18m cells compared to IEC‐18p.ConclusionsExpression of mutant NOD2 significantly decreased protein expression and disrupted the TJ resulting in a functional increase in permeability. These changes may contribute to alterations in permeability seen in CD.Support by NIH K08 GM081595
Isoform‐specific modulation of CYP450 omega hydroxylases by cyclosporine in glomerular mesangial cells
Authors: Sharma Mukut , Sharma Ram , Srivastava Tarak , Savin Virginia J. , McCarthy Ellen T. 
Published: June 2021

Cyclosprine A (CSA), an immunosuppressive agent used in the treatment of many proteinuric conditions, protects the glomerular filtration barrier. We have shown that 20‐hydroxyeicosatetraenoic acid (20‐HETE), an eicosanoid generated by the CYP4a and 4f omega hydroxylase activities, maintains and protects the glomerular filtration barrier. We hypothesize that CSA induces expression of CYP4a and/or 4f in mesangial cells to protect the filtration barrier and mitigate proteinuria. We incubated murine mesangial cells in CSA (10 nM, 100 nM, 1 μM, 10 μM) or vehicle for 1, 8 or 24 hrs. We then isolated total RNA and performed real time RT‐PCR using specific primers to measure expression of CYP4f13, CYP4a12a and CYP4a12b. CYP4f13 expression showed the greatest response to CSA treatment. At 8 hr CSA 1 μM and 10 μM increased CYP4f13 by 91% and 74%, respectively. At 24 hr CSA 100 nM, 1 μM and 10 μM increased CYP4f13 by 36%, 268% and 200%, respectively. At 24 hr, CSA 10nM and 100 nM increased expression of CYP4a12a by 75% and 88%, respectively, while CSA 10 μM appeared to suppress expression to 48% of control at 24 hr. CSA 10 μM increased expression of CYP4a12b by 85% at 8 hr; this concentration appeared to suppress expression at 24 hr. Thus, mesangial cells express CYP4a and 4f, and CSA modulates the expression of these CYP isoforms in this cell type in a time and dose‐dependent manner.Supported by NIH/NIDDK R01 DK064969.
Effects of a high vs. low carbohydrate diet on fat and carbohydrate oxidation in cats
Authors: Shoveller Anna Kate , Flickinger Elizabeth A. , Atkinson Jim L. , Duncan Ian J.H. , Gooding Margaret A. 
Published: June 2021

Low or high carbohydrate (CHO) diets (18.9 and 46.3%, LC and HC, respectively) and length of adaptation were investigated in cats (Felis catus; 10 ± 1 mo, 3 ± 1 kg). Cats received each treatment for 14 d in a crossover design and 20 h indirect calorimetry studies were conducted after acute (A; d 0), semi‐chronic (SC; d 4) and chronic (C; d 13) dietary exposure. Data were analyzed by repeated measures ANOVA and Proc Mixed.When cats consumed the HC and LC diet, Ox of the restricted nutrient exceeded intake while Ox of the nutrient in excess matched intake. Mean max energy expenditure (EE) of cats consuming the LC and HC diet were 107 and 102 kcal/kg0.67/d and occurred at a mean of 245 and 712 min post feeding, respectfully. Mean max fat (0.90 g/h) and CHO (1.42 g/h) Ox were attained at 26 and 626 min post feeding, respectfully. The changes in Ox and EE suggest that cats adapt to changes in dietary nutrient content, but may require longer than 14 d to adapt to restricted nutrient intake. Supported by: The Procter and Gamble Co., Pet Care, Ohio, USA
Positive association of total protein intake and bone mineral density (BMD) in women from the Framingham Offspring Study
Authors: Sahni Shivani , Broe Kerry E , Tucker Katherine L , McLean Robert R , Kiel Douglas P , Cupples L Adrienne , Hannan Marian T 
Published: June 2021

ObjectiveThe effect of protein on bone is controversial; further calcium intake (CA) may modify protein's effect. We evaluated the cross‐sectional association of % total energy from protein intake (TP%) with bone mineral density (BMD) at femoral neck (FN), trochanter (TR) and L2‐L4 spine (LS) in the Framingham Offspring Study, also whether CA modified any association.Methods1639 women and 1280 men completed a food frequency questionnaire and had BMD measured in 1991–95 or 1995–98. We used multivariable linear regression to examine the association of TP% with each BMD, adjusting for covariates.ResultsMean age was 60 years (SD:9.3) in women and 61 years (SD:9.4) in men. In women, positive associations were seen between TP% and each BMD [FN: β=0.0012(SE=0.0009), P=0.04, TR: β=0.0002(SE=0.0008), P=0.01, LS: β=0.002(SE=0.001), P=0.04]. No associations were seen in men (P range: 0.28–0.72). We stratified (a priori) by CA: women with <800mg/d CA showed strong associations [FN: β=0.002(SE=0.001), P=0.07, TR: β =0.002(SE=0.0009), P=0.04; LS: β=0.003(SE=0.001), P=0.07]. In women with ≥ 800mg/d CA the positive associations were not significant (P range: 0.27–0.42). No associations were seen in men (low CA group: P range= 0.15–0.50; high CA group: P range= 0.43–0.91).ConclusionIn this study higher protein intake was positively associated with BMD at multiple sites in middle aged women but not men. Longitudinal studies are needed especially to examine the role of CA in these associations.Grant Funding Source: NIH R01 AR053205, NIH R01 AR/AG 41398; and N01‐HC‐25195
Decursin, decursinol angelate decursinol inhibit pro‐inflammatory cytokine expression on β‐amyloid peptide‐induced THP‐1 cells
Authors: Li Wei , Li Li , Park Sung‐ki , Jung Sang‐won , Kim Yong‐ho 
Published: June 2021

One of the characteristic pathological features of Alzheimer disease(AD) is the inflammatory response associated with extracellular deposition of β‐Amyloid Peptide(Aβ). The most important landmark of inflammation in AD is the pro‐inflammatory cytokines, especially IL‐1β. Decursin, decursinol angelate and decursinol are the three main coumarin components purified from Angelica gigas Nakai. The monocytic THP‐1 cells and the THP‐1 derived macrophage cells were pre‐treated with 20μM, 40μM and 60μM of the three kinds of components respectively for 3 hrs, and then treated with 125nM Aβ for 12 hrs. Without cytotoxicity, pre‐incubation with decursin, decursinol angelate or decursinol has elevated the cell viability compared with the Aβ group in lactate dehydrogenase(LDH) cell viability assay. Also the three components have blocked the pro‐inflammatory cytokine IL‐1β production in western blot with a time‐dependent and dose‐dependent manner in both monocytes and macrophages, respectively. The results of these studies suggested that the three coumarin compounds isolated from Angelica gigas Nakai have great anti‐inflammatory potential, and they could be considered as therapeutic reagents in the Alzheimer disease therapy.This research is supported by Biohealth Products Research Center(BPRC) of Inje University.
Nine‐day weight loss program with high protein shakes supplemented with herbal beverage in dry mix powder or liquid form on fasting days leads to healthy weight loss
Authors: Balliett Mary , Burke Jeanmarie R , Rasmussen Oscar , Rockway Susie 
Published: June 2021

AimTo evaluate a nine‐day weight‐loss program consisting of fasting days supplemented with a novel herbal beverage in dry powder mix or ready‐to‐drink liquid form on body composition and blood parameters in healthy adults.DesignThe study randomized 42 healthy adults to one of two groups. Group 1 received herbal beverage from powder mix while Group 2 received ready‐to‐drink liquid. Both groups fasted with 64 oz of water and 16 oz of herbal beverage in two‐day intervals separated by five non‐fasted days in which subjects ate one meal and replaced two others with a meal‐replacement high‐protein shake. Measurements and blood were taken days 0 and 10.StatisticsANOVA for repeated measures was performed initially; however, no differences between groups were detected for any measure, thus, data for both groups were pooled.ResultsThe average weight loss of subjects was 6.6 lbs (3.8% of initial body weight) and was statistically significant (p<0.05) from baseline weight (174 ± 42). Waist and hip circumference decreased significantly by 0.6 and 0.7 inches, respectively, from baseline. Both lean and fat body mass decreased by 3.2 and 2.9 lbs, respectively. Total‐, LDL‐ cholesterol and TG decreased significantly by 17.8, 8.3 mg/dl and 25.6 mg/dL, respectively. Subjects lost weight and felt better about their body weight and energy level.Products and funding were provided by Isagenix International, LLC.
Modulation of Cardiac Metabolism by Beta‐Blockers During Diabetes: A Role in Apoptosis Signaling
Authors: Saran Varun V V , Sharma Vijay , Yuen Violet , Allard Michael F , McNeill John H 
Published: June 2021

Diabetic Cardiomyopathy is characterized by problems during diastole, this is due to loss of contractile tissue after apoptosis. Apoptosis may be caused by increases in oxidative stress associated with metabolic modifications.Beta‐adrenergic receptor antagonists, (β‐blockers) improve heart function. Metoprolol (met) and carvedilol (car) are clinically important β‐blockers that modulate metabolism and reduce apoptosis, car, also has antioxidant properties. We tested whether β‐blockers will reduce apoptosis and improve heart function via oxidative stress dependant and or independent pathways.We employed a Streptozotocin (STZ) induced rat model of type 1 diabetes. This model has been shown to develop diastolic dysfunction. STZ was delivered at 60mg/kg body weight. Met and car were delivered at a rate of 15 and 10mg/kg/day respectively. In order to assess the significance of car's antioxidant abilities, we included groups where met treatment was supplemented with vitamin C at 1000mg/kg/day.Analysis indicates induction of diabetes in STZ animals. β‐blocker treatment caused a significant reduction in heart rates. Remaining analysis includes assessment of in vivo and ex vivo heart function, metabolic flux, apoptosis, expression analysis of effecter proteins involved in apoptosis, and measurement of oxidative stress.Funding for this research was provided by the Canadian Institutes of Health Research
P120‐catenin Suppresses the Inflammatory Response in Endothelial Cells
Authors: O'Donnell James John , Cheng Feng , Zhang Jihang , Zhuge Yan , Holian Oksana , Lum Hazel 
Published: June 2021

P120‐catenin (p120ctn) promotes cell‐cell adhesion at the adherens junction of vascular endothelium. Emerging evidence from fields in cancer and development suggests that p120ctn can additionally repress transcription. We therefore investigated whether p120ctn of human endothelial cells has transcriptional function and to explore potential gene targets regulated. Results indicated that siRNA‐mediated depletion of p120ctn doubled promoter reporter luciferase activities of transcription factors NFκB, AP‐1, and Kaiso, which were associated with increased phosphorylation of ERK1/2. Immunofluorescence showed that loss of p120ctn increased NFκB nuclear localization, further confirming transcriptional activation. Treatment of endothelial cells with PD98059, an ERK1/2 inhibitor, abrogated the NFκB translocation, suggesting ERK1/2‐dependence. A known gene target of NFκB and AP‐1 is ICAM‐1, and we found that p120ctn loss doubled ICAM‐1 mRNA and tripled ICAM‐1 protein expression. Our findings provide strong evidence that p120ctn suppresses transcriptional regulation in endothelial cells and may be critical for suppressing pro‐inflammatory activity. The study is supported by NIH HL093715.we investigated whether this upregulation is through pro‐inflammatory signaling molecules Extracellular Signal‐regulated kinases 1 and 2 (ERK1/2).
Some biochemical parameters in hemolymph of Garden snail (Helix pomatia L.) in the region of power plants of Kosovo
Authors: Halili Fetah , Bislimi Kemajl , Gashi Agim M , Bajraktari Ismet D , Mazreku Ilir , Aliu Naser 
Published: June 2021

In current work the concentration of glucose, total proteins, cholesterol and the activity of the alkaline phosphatase in hemolymph of local population of Garden snail Helix pomatia L.(N=20), in the region contaminated by the power plants of Kosovo in Obiliq, was analyzed. The snails of control group were taken from the region of Gjilan far away from polluted area. The preliminary investigation results have shown that the concentration of the cholesterol in the hemolyph of snails from the polluted region was significantly higher whereas the activity of the enzyme alkaline phosphatase significantly lower in comparison with the snails of the control group. There was no indication of difference regarding the glucose and the total protein concentration between the analyzed snail groups.The investigation shows that the Garden snail can serve as bioindicator, whereas the changing of the hemolymph chemistry as marker for the biochemical indication of the environmental pollution effects.
Amiodarone and N‐ethyl‐amiodarone exert opposing allosteric effects via a novel site on muscarinic receptors
Authors: Stahl Edward , Ellis John 
Published: June 2021

Allosteric modulation provides several advantages over the classical (orthosteric) approach to receptor activation; further, the characterization of new allosteric sites provides additional opportunities for the development of subtype‐selective and functionally selective compounds. We have been investigating the allosteric actions of amiodarone and N‐ethyl‐amiodarone (NEA) at muscarinic receptors. Previous studies have demonstrated that amiodarone interacts with a site that is distinct from the one that has been defined by gallamine.We have shown that amiodarone enhances stimulation of [3H]arachidonic acid release induced by agonists acting at Gq‐coupled muscarinic receptors. Evaluation of this action in light of Hall's allosteric two‐state model indicates that amiodarone's enhancement of agonist efficacy is tempered by a concomitant reduction in agonist binding affinity. The enhancement of efficacy is attenuated by NEA but not by the orthosteric antagonist N‐methylscopolamine; further evaluation of this finding using an elaboration of Hall's model suggests that amiodarone and NEA exert their functional effects through a common allosteric site.In conclusion, we have demonstrated that amiodarone and NEA interact allosterically with a novel, extracellular, site on muscarinic receptors, through which they modulate agonist potency and efficacy in a complex manner.
Mechanism of Peripheral NMDA Receptor‐Mediated Pressor Response in Conscious Rats
Authors: McGee Marie A , Abdel‐Rahman Abdel 
Published: June 2021

Despite its expression in vascular and cardiac tissues, the role of peripheral NMDARs in blood pressure control in conscious animals has not been examined. This study is the first to report a dose (125, 250, 500 and 1000 μg/kg)‐related pressor response elicited by systemic NMDA in male Sprague‐Dawley rats. Femoral vessels were catheterized 2 days prior to NMDA injection and NMDA was administered i.v. at 15 min intervals (n=6). In a subsequent experiment, we tested the hypothesis that an NMDA‐evoked generation of vascular reactive oxygen species (ROS) underlies the pressor response. A submaximal dose (250 μg/kg) of NMDA or its vehicle (saline) was administered i.v. in 2 groups of conscious rats and vascular (aorta) and cardiac tissues were collected at the conclusion of the experiment. The NMDA‐treated group displayed a significant increase in MAP when compared to the control group (n=8 each, p<0.05). Tissue ROS and NO levels were analyzed using dihydroethidium (DHE) and 4‐amino‐5‐methylamino‐2′7′‐dichlorofluoroscein diacetate (DAF‐FM) fluorometry. The pressor response elicited by peripheral NMDAR activation was associated with elevated vascular ROS. The increase in vascular ROS, which approached statistical significance when compared with control values, seems to support the tested hypothesis. Interestingly, however, vascular NO was increased significantly by peripheral NMDAR activation. These findings are the first to demonstrate a peripheral NMDAR‐evoked pressor response and yield insight into possible molecular mechanisms that contribute to this response.This research was supported by East Carolina University and NIH grant R01 AA07839.
Mechanism of target specialization of prokaryotic transcription factors GreA, GreB and DksA
Authors: Parshin Andrey V. , Lee Jookyung , Borukhov: Sergei 
Published: June 2021

Bacterial transcription factors GreA, GreB and DksA regulate RNA polymerase (RNAP) function by acting through its secondary channel. GreA and GreB stimulate RNAP intrinsic nucleolytic activity, thereby suppressing transcriptional pause and arrest, enhancing transcription fidelity and helping promoter escape. DksA activates and/or inhibits transcription both in vivo and in vitro by destabilizing RNAP open promoter complexes. We characterized the molecular interfaces of GreA‐RNAP and DksA‐RNAP complexes using site‐specific protein‐protein crosslinking and site‐directed mutagenesis. We also determined the binding affinities of Gre/DksA towards different transcription complexes and analyzed their functional activities by in vitro transcription assays. We identified the key residues in Gre, DksA and RNAP secondary channel required for specific Gre/DksA‐RNAP interactions. Based on our data, we created plausible structural models of Gre‐ and DksA‐RNAP complexes. In the models, Gre and DksA bind to RNAP β’ N‐terminal coiled‐coil element. However, the contact residues for Gre and DksA on β’ are distinct. DksA coiled‐coil interacts with the β’ conserved G‐loop element. The conformational changes in the G‐loop define the binding of GreA to RNAP. Unlike Gre factors, DksA does not bind to elongation complexes and does not compete with GreA during transcription. These results indicate that Gre and DksA target different classes of transcription complexes in vivo, most likely, depending on the conformation of the flexible G‐loop element of RNAP.This work was supported by National Institute of Health.