bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total arterial compliance estimated from the time constant of aortic pressure decay: the influence of downstream pressure
Authors: Chemla Denis , Nitenberg Alain 
Published: June 2021

The influence of downstream pressure (Po) on total arterial compliance (C) was studied in 16 adults (14 M, 2F; aged 44±16 yrs) undergoing left heart high fidelity pressure catheterization. A two‐element RC model of the circulation was assumed, where R is the vascular resistance. The time constant (Tau = RC) of the monoexponential fit of diastolic aortic pressure decay was calculated by using either the standard, semilogarithmic method with zero pressure asymptote, or two methods with variable pressure asymptote, namely the best‐fit method and the derivative method. Cardiac output was measured by the thermodilution technique. Diastolic aortic pressure was 82±10 mmHg. The best‐fit method and the derivative method led to similar value of Po (71±12 vs 75±12 mmHg), Tau, R and C. As compared with the semilogarithmic method, the best‐fit method led to 74% lower Tau (353±106 vs 1372±106 msec; P<0.05). When substituting Po for central venous pressure, the R was 72% less (0.42±0.17 vs 1.51±0.61 mmHg.sec.mL−1; P<0.05). This resulted in C that was 18% less (0.83±0.38 vs 1.02±0.40 mL.mmHg−1; P<0.05). The high Po value documented here was consistent with recent experimental and clinical findings suggesting that a Starling resistor mechanism could be present in vivo at the arteriolar precapillary level of the various systemic vascular beds. This may significantly impact on the clinical estimation of arterial load.Source of research support: University.
Angiotensin‐(1‐7) stimulates high atrial pacing‐induced ANP secretion
Authors: Shah Amin , Gul Rukhsana , Yuan Kuichang , Shan Gao , Oh Young‐bin , Kim Uh‐Hyun , Kim Suhn Hee 
Published: June 2021

Angiotensin‐(1‐7) [Ang‐(1‐7)] has many beneficial roles in cardiovascular physiology, counterbalancing Angiotensin II functions. It is considered as one of the theurapeutic agent for cardiovascular diseases in the future. The aim of the present study is to elucidate the modulatory role of Ang‐(1‐7) in atrial natriuretic peptide (ANP) secretion using isolated perfused beating rat atria and cardiac hypertrophied rat model. Ang‐(1‐7) (10−8, 10−7, and 10−6M) increased the ANP secretion and ANP concentration in a dose‐dependent manner at high atrial pacing (6.0 Hz) with an increased cGMP amount. However, Ang‐(1‐7) did not cause any changes in atrial parameters at low atrial pacing (1.2 Hz). An antagonist of Mas receptor or inhibitors of phosphoinositide 3‐kinase (PI3K), protein kinase B (Akt), or nitric oxide synthase pretreatment blocked the increase of high atrial pacing‐induced ANP secretion by Ang‐(1‐7). The inhibition of Na+/H+ exchanger‐1 (NHE‐1) and calcium/calmodulin‐dependent kinase II (CaMKII) showed the similar result. Ang‐(1‐7) did not show any changes in intracellular calcium concentration in quiescent atrial myocytes. However, Ang‐(1‐7) attenuated an increase of intracellular calcium concentration induced by angiotensin II. Intravenous infusion of Ang‐(1‐7) increased the plasma concentration of ANP by 2‐fold without changes in blood pressure and heart rate in isoproterenol‐treated rats but not in control rats. Ang‐(1‐7) attenuated cardiac hypertrophy induced by isoproterenol. These results suggest that Ang‐(1‐7) increased the ANP secretion at high atrial pacing via Mas/PI3K/Akt pathway and the activation of NHE‐1 and CaMKII.Supported by the KOSEF (R13‐2008‐005‐00000‐0).
ESTROGEN RECEPTOR CONTRIBUTES TO SEX DIFFERENCES IN ACUTE KIDNEY INJURY
Authors: Ruiz Arnaldo Lopez , Juncos Ramiro , Chandrashekar Kiran , Liu Ruisheng , Reckelhoff Jane F. , Juncos Luis A. 
Published: June 2021

Gender may influence the susceptibility and severity of various renal diseases. We evaluated sex difference, and the role of the estrogen receptor, in the hemodynamic and inflammatory responses to renal ischemia‐reperfusion induced‐acute kidney injury (I/R‐AKI). Adult Sprague‐Dawley rats were randomized into 4 groups (n=6–7/group), 1) Male Sham (M‐SHAM), 2) Female Sham (F‐SHAM), 3) Male‐ I/R‐AKI (M‐I/R‐AKI), 4) Female I/R‐AKI (F‐I/R‐AKI). I/R‐AKI was induced by bilateral clamping of the renal pedicles for 40min. Measurements were obtained 72 hrs after I/R‐AKI.

Cortical‐RBF (TPU)
OM‐RBF (TPU)
CrCl (ml/min/g)
NGAL (UI/ml)
IL‐10 (pg/mg)
HO Activity (pM Bilir./mg)

M‐SHAM (6)
34.7±4.5
16.9±3.0
1.00±0.03
700±181
1.9±0.1
52±8

F‐SHAM (7)
32.9±1.4
22.6±1.0
1.02±0.10
1400±240#
3.1±0.3#
90±5#

M‐I/R‐AKI (6)
13.2±2.6
11.4±1.3
0.16±0.01
3400±138
0.9±0.05
213±10

F‐I/R‐AKI (7)
15.3±2.8
17.6±1.5*
0.47±0.03*
4087±47*
2.1±0.1*
553±37*

(n). Data are Mean±SEM.
p<0.05 vs M‐I/R‐AKI.
p<0.05 vs M‐SHAM
CrCl = Creatinine Clearance; OM‐RBF = Outer Medullary‐RBF

In addition, estrogen receptor blockade in females decreased IL‐10 and HO activity, and worsened the parameters of renal function. Our data suggest that females, via estrogen receptors, have enhanced tissue protective factors (IL‐10 and HO), which may contribute to less severe impairment of hemodynamic and functional abnormalities after I/R‐AKI.
Sex hormones negatively modulate STIM‐1/Orai‐1 activity during hypertension: focus on calcium regulation
Authors: Giachini Fernanda , Lima Victor V , Carneiro Fernando S , Webb R. Clinton , Tostes Rita C 
Published: June 2021

We recently showed that augmented vascular activation of STIM1/Orai1 pathway in male hypertensive rats contributes to the sex‐related impairment in intracellular Ca2+handling. We hypothesized that sex hormones contribute to the vascular protection in female hypertensive rats, via a decrease in STIM1/Orai1 activation. Endothelium‐denuded aortic rings from ovariectomized (OVX, for 15 weeks) or intact (SHAM) female stroke prone spontaneously hypertensive (SHRSP) and Wistar‐Kyoto (WKY) rats, were used to functionally evaluate Ca2+ influx‐induced contractions [upon depletion and reloading of intracellular Ca2+ (Ca2+loading period)]. Sarcoplasmic reticulum Ca+2 ATPase was inhibited with thapsigargin (10μM). During the Ca2+loading period, force development was augmented in aortas from SHRSP OVX vs. other groups and increased contraction was normalized with gadolinium (100μM, CRAC channel inhibitor), as well as blockade of STIM1 and Orai1 with neutralizing antibodies. Intracellular Ca2+ store release was increased in aortas from SHRSP vs. WKY, but no differences were observed between SHAM and OVX. Orai1 and STIM1 expression were increased in aortas from SHRSP OVX vs. the other groups. We conclude that sex hormones negatively modulate the expression and activity of STIM1/Orai1, contributing to the sex‐related differences in intracellular Ca2+ handling.Financial support: American Heart Association (AHA 09GRNT2250383)
Anoxia‐mediated decrease in whole‐cell conductance and identification of putative background K+‐like currents in anoxia‐tolerant turtle liver
Authors: Hogg David William , Buck Leslie Thomas 
Published: June 2021

To survive months of anoxia painted turtles (Chrysemys picta bellii) suppress ATP utilizing pathways, enabling metabolic demands to be met through anaerobic ATP production. Ion pumping is a major ATP utilizing pathway and a decrease in membrane permeability to ions or ion channel arrest (CA) is thought to reduce ATP demand. Evidence supporting CA in anoxic turtle brain includes a 50% decrease in both major excitatory glutamatergic receptor/channels ‐ AMPA and NMDA. Recently we have shown that a 25% increase in whole‐cell conductance (Gw) occurs and this is due to an increase in GABA‐A receptor currents that clamp resting membrane potential (MP) at a hyperpolarized state preventing action potential generation. In non‐excitable anoxic liver MP is maintained while Na+/K+ ATPase activity decreases by 75%, indirectly providing evidence for CA.Using a liver slice model, we investigated anoxia‐mediated CA directly using whole‐cell and single‐channel electrophysiological techniques. We found anoxia induces a 16% depolarization of MP, 25 ± 5 mV to 21 ± 0.2mV and a 20 ± 3% decrease in Gw. We also identified a 3–5 pA potassium current that was active at normoxic MP and upon anoxia activity decreased by 40%. We conclude that 1) in liver Gw decreases with anoxia to reduce the ATP cost of maintaining concentration gradients, 2) anoxia modulates potassium currents with characteristics similar to background potassium channels.
Relating muscle phenotype to in vivo mitochondrial function
Authors: Schmitz Joep P , van Riel Natal A , Nicolay Klaas , Hilbers Peter A , Jeneson Jeroen A 
Published: June 2021

A decreased mitochondrial function has been observed during aging and type II diabetes. Understanding of the mechanisms underlying this decrease is complicated by the vast amount of proteins potentially involved. We aim on developing a computational model to estimate the contribution of a change in individual protein concentrations to in vivo mitochondrial function. A computational model of skeletal muscle energy metabolism was developed and validated with 31P MRS data recorded in human quadriceps muscle. The multi cellular model contains three distinct cell types: I, IIA and IIX, respectively. Each cell incorporates detailed descriptions of mitochondrial and glycogenolytic ATP synthetic pathways, ATP buffers and ATP consumption.The model was then applied to analyze how phenotype changes reported in literature affected mitochondrial function. ANT concentration, mitochondrial volume content and muscle fiber type composition influences mitochondrial function the most significantly, whereas, the influence of concentrations of TCA cycle proteins, oxidative phosphorylation complexes and proton leak was relative small.It was concluded that this computational approach provides unique opportunities for investigating the relation between muscle phenotype and in vivo mitochondrial function and as such may contribute to an improved understanding of aging and type II diabetes.
Elevated fatty acid availability after exercise increases intramyocellular triglyceride content by enhancing capacity for fatty acid flux into skeletal muscle
Authors: Newsom Sean Alec , Schenk Simon , Li Minghua , Everett Allison Clare , Horowitz Jeffrey F 
Published: June 2021

We previously reported a single exercise session protects against fatty acid (FA)‐induced insulin resistance, perhaps via augmented intramyocellular triglyceride (IMTG) synthesis. The aim of this study was to examine the effect of elevated FA availability after exercise on the regulation of IMTG metabolism. After exercise (90min at 65% VO2peak) 7 healthy women (BMI: 23±1 kg/m2) were infused overnight (16h) with either a lipid and heparin solution (LIP; 0.11 g fat/kg/h) or saline (SAL), and we obtained a skeletal muscle sample the next morning. Despite a 4‐fold increase in overnight plasma [FA] during LIP, whole‐body FA oxidation was not elevated (P=0.35). Conversely, IMTG increased by ~30% during LIP vs SAL (49±3 vs 38±3 umol/g dw; P=0.04), accompanied by ~25% greater localization of the FA transporter, CD36 to the muscle membrane (P<0.01) and ~8% increase in the activity of the IMTG synthetic enzyme glycerol‐3‐phosphate acyltransferase (GPAT; P=0.01). We found no difference in GPAT and diacylglycerol acyltransferase (DGAT) protein abundance, or DGAT activity between treatments. Our findings suggest augmented capacity for FA flux into muscle (i.e., via membrane‐bound CD36), perhaps together with a slight, yet significant increase in activity of a key IMTG synthetic enzyme (GPAT) may enhance IMTG storage when FA availability is high after exercise.Supported by NIH Grant #R01 DK071955
Cardiorenal Sympathetic Denervation and Baroreflex Failure in Parkinson Disease with Orthostatic Hypotension
Authors: Goldstein David S , Sewell LaToya , Holmes Courtney S 
Published: June 2021

BackgroundAbout 40% of Parkinson disease (PD) patients have orthostatic hypotension (OH). We tested whether cardiac and renal sympathetic denervation and baroreflex failure characterize PD+OH.MethodsPD patients were stratified into two groups based on presence or absence of OH. Interventricular septum and renal cortex 6‐[18F]fluorodopamine‐derived radioactivity by positron emission tomography were expressed as ratios of liver radioactivity. Baroreflex‐cardiovagal function was assessed by interbeat interval‐systolic pressure relationships during the Valsalva maneuver and baroreflex‐sympathoneural function by fractional orthostatic increments in plasma norepinephrine (NE).ResultsThe PD+OH group had low mean septum:liver and renal cortex:liver ratios (p<0.0001, p=0.02), low baroreflex‐cardiovagal gain (p<0.0001), and small orthostatic increments in plasma NE (p<0.0001). Baroreflex‐cardiovagal gain and the fractional increment in plasma NE were closely related to septum:liver ratios (p<0.0001; p=0.009) and weakly related to cortex:liver ratios (p=0.05; p=0.09). Septum:liver and renal cortex:liver ratios were positively correlated (p=0.0001).ConclusionsIn PD, renal and cardiac noradrenergic denervation and baroreflex failure are associated with OH.Source of research support: Intramural Research Program, NINDS, NIH
Skeletal muscle: Missing link between exercise and NF‐kappaB pathway regulation in Alzheimer's Disease?
Authors: Lloyd Jesse William , Kelleher Andrew , Heckstall Ebony , Holohan John , Keslacy Stefan 
Published: June 2021

IntroductionAlzheimer's Disease (AD) is associated with muscle wasting and low‐grade chronic inflammation. Exercise upregulates anti‐inflammatory gene expression in skeletal muscle. NF‐κB is a key transcription factor of the inflammatory process. Hypothesis: We hypothesize that exercise, in the AD physiological milieu, will induce an NF‐κB‐depend anti‐inflammatory gene expression in skeletal muscle. APP/PS1 mice, that develop Amyloid β‐containing plaques, were exposed to running wheels for 4 weeks (EX) or were sedentary (SED). NF‐κB‐dependent gene expression was quantified using a gene array via qRT‐PCR.ResultsEX demonstrated high level of exercise, 10000 rpd. Total protein concentrations in Soleus (SOL), Gastrocnemius (GM) and Extensor Digitorum Longus (EDL) were similar between EX and SED. NF‐κB/P65 expression decreased in EDL and GM of EX. IκB follows the pattern of P65 inhibition and increased in SOL, EDL and GM of EX. Downregulation of several NF‐κB‐dependent inflammatory genes occurred in SOL of EX (Casp1, Smad3, and Tlr1/7). Genes associated with NF‐κB and involved in immune response (Crebbp, Irf1, Myd88, Slc20a1, Stat1 and TbK1) and cell growth (Akt1, Ccl2, Atf2) were upregulated in SOL of EX.ConclusionThe beneficial effects of exercise in AD may be due to a regulation of inflammation and immune system‐related genes expression originated from skeletal muscle.
Mesenchymal stem cells isolated from a novel equine tissue exhibit embryonic molecular markers and adipogenic differentiation potential
Authors: Isquith Jane Marie , Shaw Kelly , Shaw Karen , Peterson Daniel , Burd Matthew 
Published: June 2021

Mesenchymal stem cells (MSC) have been isolated from equine tissues, most notably adipose and bone marrow. On the basis of ability for self‐renewal, molecular marker expression and differentiation potential, we characterized MSCs isolated from a tissue not yet explored in the equine. After isolation, MSCs were maintained in culture for 25 passages before senescence was observed. Reverse transcription‐PCR revealed embryonic transcription factor Oct4 mRNA, as well as mRNA for fucosyltransferase 4 and ST3 B‐galactoside α 2,3 sialyltransferase 2, two enzymes responsible for synthesis of embryonic surface markers SSEA1 and SSEA4, respectively. Treatment with insulin, dexamethasone, indomethacin and isobutylmethylxanthine led to increased oil red O staining (P<0.05) indicating successful adipogenic differentiation. These data indicate the stem‐like nature of these cells and their successful isolation from this tissue source. However, further characterization is needed to determine their full potential.Partially funded by College of Agriculture, Food and Environmental Science, Cal Poly San Luis Obispo
Role of AT1 receptors over the oxidative stress in chronic renal failure (CRF)
Authors: Dugaich Adriana Poli Castilho , Mantovan Nubia Fardin , Boim Mirian Aparecida , Ribeiro Daniel Araki , Campos Ruy Ribeiro , Bergamaschi Cassia Toledo 
Published: June 2021

CRF is a progressive condition marked by deteriorating kidney function over time. Elevated blood pressure, renin‐angiotensin system and the imbalance of antioxidant defenses are involved in the progression of renal diseases. The aim of this study was to evaluate the effects of chronic treatment with angiotensin AT1 receptor blockade (Candesartan) in the oxidative stress and evolution of CRF. Wistar rats were divided in 3 groups: control (C, n=6), CRF (n=6) and CRF + Cand (n=6). CRF was induced by the 5/6 nephrectomy model. Treatment with Cand, 25 mg/Kg VO (2 weeks, daily) started 6 weeks after surgery. Creatinine clearance (CrCl) and TBARS (indicative of oxidative stress) were evaluated. Animals of CRF presented a reduction in CrCl and Cand treatment improves this effect (C 2,1±0,2 x CRF 0,9 ±0,1 x CRF + Cand 1,5±0,2 ml/min). Plasmatic levels of TBARS are raised in CRF and Cand treatment normalized this values (C 2,0±0,2 x CRF 3,6 ±0,06 x CRF +Cand 1,0 ± 0,3 nmoles/ml). These results suggest that blockade of AT1 receptor reduces oxidative stress and improve renal function in CRF rats. The reduction of oxidative stress can be an important factor against progression of renal disease.Supported by: CNPq
DDAH 2 maintains blood pressure and kidney function in response to ADMA administration in both control and diabetic rats
Authors: Palm Fredrik , Lou Zaiming , Welch William J , Wilcox Christopher S 
Published: June 2021

Asymmetric dimethylarginine (ADMA) inhibits nitric oxide synthases and is increased in diabetes. Dimethylarginine dimethylaminohydrolase (DDAH) 2 metabolizes ADMA and is expressed at different intrarenal sites, including the vasculature. We hypothesize that DDAH 2 prevents vasoconstriction and maintains kidney function in response to elevated ADMA levels. Control and diabetic rats (n=8–9/group) were injected with either vehicle or siRNA against DDAH‐2. Mean arterial blood pressure (MAP) and kidney function in response to exogenous ADMA administration were measured 48h later. siRNA reduced DDAH‐2 protein expression by −60% in both groups. MAP was only elevated in diabetic rats receiving siRNA (+10 mmHg). ADMA increased MAP in all groups compared to vehicle injected controls (+13 to 17 mmHg). Both diabetic groups had increased glomerular filtration rates (2.6±0.1 and 3.0±0.2 vs 1.6±0.2 and 1.5±0.3 ml/min/kidney; P<0.05) and ADMA reduced GFR in only the siRNA treated groups (diabetics −23% and controls −43%). Baseline renal blood flow (RBF) was decreased in both siRNA groups compared to vehicles (control 9.9±0.7 vs 7.5±0.7 and diabetes 9.8±0.9 vs 8.7±0.5 ml/min/kidney) ADMA reduced RBF in siRNA controls (−11%), vehicle diabetics (−11%) and in siRNA diabetics (−20%).DDAH‐2 protects the renal vasculature from vasoconstriction and subsequently increased MAP and reduced GFR in response to elevated ADMA levels in both control and diabetic rats. These results provide further evidence that DDAH 2 and ADMA may influence kidney function. Funding: NIH/NIDDK DK077858.
Secular changes in growth of Polish schoolboys from 1955 to 1988 in historic context
Authors: Bielecki Emily Marcene , Haas Jere D , Hulanicka Barbara 
Published: June 2021

BackgroundAnthropometric data, especially in children, has been widely used to evaluate the effects of socioeconomic conditions on growth and well‐being.ObjectiveThe aim of this analysis is to describe the changes in height, weight and body mass index (BMI) in Polish schoolboys born between 1937 and 1981 from a historic perspective.MethodsData from four nation‐wide cross‐sectional surveys (1955, 1966, 1978, and 1988) were analyzed. Height, weight and BMI were converted to standardized scores using the LMS method applied to the 2000 National Center for Health Statistics growth reference.ResultsIn each consecutive survey year schoolboys (7–18 years) are generally taller and heavier than the same aged boys in the previous survey year. Within survey years, there is a decline with age into puberty in height Z‐scores. The prevalence of obesity is low and underweight appears to have greater relative importance.ConclusionsHistorical context of economic changes supports that adolescents measured within each survey year likely experienced an adverse environment during their first few years of life. This was partly compensated during later growth in selected birth cohorts that were measured over a 10 to 12 year interval. Some, but not all of the age dependant decline in the Z‐scores can be explained as an artifact of the reference.Research support came from Fulbright and the NS Meinig Professorship at Cornell.Grant Funding Source: Research support came from Fulbright and the NS Meinig Professorship at Cornell.
Visualization of virtual screening results on tiled display walls (TDW)
Authors: Lau Christopher D. , Levesque Marshall J. , Date Susumu , Chien Shu , Haga Jason H. 
Published: June 2021

Virtual screening has facilitated the drug discovery process through the use of molecular simulations to computationally identify inhibitors and has yielded a tremendous amount of data. These results cannot be utilized in laboratory experiments until they are analyzed manually to identify anomalies, redundant chemical structures, and false positives. For this reason, a new, high‐throughput method to analyze the results of virtual screenings is needed, thereby accelerating the drug discovery process.We have developed, deployed, and tested a modified version of ViewDock (named ViewDock TDW) on two separate TDW configurations. This tool allows a user to simultaneously visualize, group, compare, and analyze dozens of ligand‐receptor interactions on a TDW. To achieve this it was necessary to modify its communication with the molecular visualization program Chimera and create several other shell, python and perl scripts to enable the graphic user interface. ViewDock TDW preserves the functionality of the Chimera software, allowing for rotation, zoom, view angle, protein surface visualization, and calculation of hydrogen bonds. The program also enables global control over all ligand‐receptor models as well as specific control for commands to be sent to individuals or groups of ligand‐receptor pairs on the TDW. This program will help greatly in the visualization and analysis of virtual screening data.
In‐silico identification of high potential SSH‐2 specific inhibitors
Authors: Mui Matthew K. , Levesque Marshall J. , Chien Shu , Haga Jason H. 
Published: June 2021

Cell growth and movement are controlled in part through the activation of a dual specificity phosphatase (DSP) called Slingshot‐2 (SSH‐2). SSH‐2 is known to contribute to the progression of cancer and Alzheimer's disease. For this reason, finding a specific inhibitor for SSH‐2 may have a profound impact in clinical treatments for different diseases. This study eliminates the need to manually test a very large chemical compound space by employing grid computer technologies in virtual molecular docking experiments to identify a list of high potential SSH‐2 inhibitors.Binding affinities were determined in the in‐silico experiments using a previously established grid‐computing workflow that uses the molecular docking simulation software, DOCK 6.0. The results from five DSP screenings, specifically SSH‐2, VHR, VH3, PTEN and KAP, suggest that 3‐[(4,5‐dimethoxy‐3‐oxo‐1H‐isobenzofuran‐1‐yl)amino]‐4‐methyl‐benzoic acid shows the highest affinity for SSH‐2, but lowest affinity for the other DSPs, among the best 100 SSH‐2 binding compounds. These results indicate that this compound has high specificity towards SSH‐2. Although these results must be confirmed through wet bench testing, this study eliminates compounds that are not likely to bind or show high specificity for SSH‐2 and provides a foundation for the analysis of molecular interactions of chemicals with SSH‐2.