bluuebunny/crossref_metadata_2025_split huggingface dataset:
A proton‐independent function of ASIC in Ciona intestinalis
Authors: Coric Tatjana , Passamaneck Yale J. , Zhang Ping , Di Gregorio Anna , Canessa Cecilia M. 
Published: June 2021

Acid‐Sensitive Ion Channels (ASICs) are neuronal‐specific voltage‐insensitive sodium channels gated by extracellular protons. ASIC functions in mammals include nociception, mechanosensation and modulation of synaptic transmission. However, the answer to what role protons play in mediating the effects of ASIC remains elusive. In this work we have examined ASIC from the ascidian Ciona intestinalis: a simple chordate organism with larval nervous system highly similar to the one of higher vertebrates. We show that Ciona has a single ASIC gene that gives rise to two spliced forms. CiASIC is expressed in most neurons of the larva, but absent in the adult nervous system. Despite sequence similarity with mammalian ASICs, CiASIC is proton‐insensitive when examined in heterologous systems or in larval neurons; the latter rules out the possibility that proton‐sensitivity is conferred by particular factors present only in Ciona neurons. Downregulation of CiASIC transcript by dsRNA disrupted the regular pattern of larval swimming, implying that proton‐independent mechanisms mediate the effects of ASIC in vivo. Together the data identify ASIC as a channel distinctive of chordate nervous system, and show that protons are not essential for ASIC function.This work was supported by NIH RO1DK054062.06A1 and AHA GIA grants to CC, NIH/NICHD R01HD050704 to ADG and APS Postdoctoral Fellowship in Physiological Genomics to TC.
Plasma adiponectin concentration is strongly associated with VLDL‐TG catabolism in postmenopausal women
Authors: Lapointe Annie , Tchernof André , Lamarche Benoit , Piché Marie‐Ève , Weisnagel John , Bergeron Jean , Lemieux Simone 
Published: June 2021

Objective: To investigate associations between plasma adiponectin concentration and VLDL‐TG secretion and catabolism in 30 postmenopausal women.Methods: Plasma adiponectin concentration was measured by ELISA. Insulin sensitivity was assessed by a 2‐h euglycemic‐hyperinsulinemic clamp. Fasting plasma glucose (FPG) and 2‐hour plasma glucose (2hPG) were measured during an OGTT. The VLDL‐TG total secretion rate (TSR) and the VLDL‐TG fractional catabolic rate (FCR) were measured by electron impact ionization gas chromatography‐mass spectrometry. The MIDA approach was used to measure VLDL‐TG TSR following a 10h‐infusion of [1‐13C] acetate and the calculation of VLDL‐TG FCR was based on the monoexponential decrease of TG‐[2H5] glycerol values obtained following the administration of a 2H5‐glycerol bolus.Results: Plasma adiponectin concentration was negatively associated with VLDL‐TG TSR (r=−0.42; p<0.02) and positively with VLDL‐TG FCR (r=0.60; p<0.0005). This latter association remained significant after statistical adjustments for insulin sensitivity, HDL‐C, TG, FPG and 2hPG. In a multivariate model, plasma adiponectin level was the best predictor of VLDL‐TG FCR.Conclusion: Elevated plasma adiponectin concentration is associated with favourable VLDL‐TG metabolism. This study was supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada.
Non‐NMDA receptor activation in the Nucleus Tractus Solitarius (NTS) increases ventilatory drive
Authors: Carr J. Austin , Fu Zhenxing , Powell Frank L. 
Published: June 2021

Previous studies showed an important role for N‐methyl‐D‐aspartate (NMDA) receptors but not non‐NMDA receptors in the NTS in the hypoxic ventilatory response (HVR) of awake rats. We hypothesized that plasticity of non‐NMDA receptors in the NTS is necessary for ventilatory acclimatization to hypoxia, which increases normoxic ventilatory drive and the acute HVR. To test this, we microinjected artificial CSF or NBQX in the NTS (4 mM in 50 nL, bilaterally) of normoxic control rats (CON, n=7) and chronically hypoxic rats (CH, n= 3, PIO2 = 70 Torr for 7 days) and used barometric pressure plethysmography to measure ventilation. Microinjection sites were identified by colloidal gold microinjections after the experiment. Ventilation (ml/(kg min) was (mean + sem):Non‐NMDA receptor blockade significantly (P<0.05) decreased ventilation under all conditions with no significant interactions between drug and treatment or inspired O2. Ventilatory changes resulted from significant effects on breathing frequency but not tidal volume. Hence, non‐NMDA receptors in the NTS are important for ventilatory drive under normoxic and hypoxic conditions but they are not solely responsible for ventilatory acclimatization to hypoxia.Supported by R01‐HL081823 (FLP) and The American Physiological Society (JAC).
Effects of combined strength and endurance training on the expression of leptin receptors in human skeletal muscle
Authors: Olmedillas Hugo , Fuentes Teresa , Delgado‐Guerra Safira , Guadalupe‐Grau Amelia , Bernales Oscar , Dorado Cecilia , Santana Alfredo , Guerra Borja , Calbet Jose Al 
Published: June 2021

Purpose. To determine if a sustained reduction in of plasma leptin concentration causes an alteration in the protein expression level of its receptors in human skeletal muscle.Methods. Fifteen males ((mean ± SD), age: 35 ±5.1 years; height: 176 ±3.6 cm; body mass: 79.2 ± 7.4 kg and percentage of body fat 22.6 ± 5.4%) participated in a 12‐week weightlifting training program. Pre and post‐training muscle biopsies were obtained from the m. vastus lateralis to determine the expression of the leptin receptor (OB‐R) protein isoforms by Western blot (J Appl Physiol. 2007 102:1786–92). Body composition was determined by DXA.Results. Training resulted in lower percentage of body fat was (from 22.5 ± 5.4 to 21.1 ±3.7 %, P = 0.06) and leptin concentration (from 9.0±7.7 to 5.7±3.7 ng/mL, P<0.05). The changes in leptin serum concentration correlated with the changes in the percentage of body fat mass (r = 0.66, p<0.05). However, non‐significant changes were observed in the expression level of the 170KDa isoform of the LR (0.77±0.2 vs. 0.85±0.5, P = 0.499) nor in the 128KDa (0.50±0.57 vs. 0.68±0.72, P=0.372) and 98KDa isoforms (1.75±1.27 vs. 1.76±2.08, P= 0.984) in skeletal muscle.Conclusion. Skeletal muscle OB‐R expression is not modified by strength training, despite a reduction in fat mass and serum leptin concentration. These findings are compatible with increased leptin sensitivity after strength training.
Divergent myofibrillar protein synthesis and signalling in skeletal muscle in response to light and heavy resistance exercise loading
Authors: Holm Lars , van Hall Gerrit , Rose Adam J , Doessing Simon , Richter Erik A , Kjaer Michael 
Published: June 2021

Objective. By standardizing exercise volume (intensity times repetitions), we investigated the isolated effect of concentric muscle contraction intensity on the anabolic response in the working skeletal muscle. One leg performed a light resistance exercise (LE) load at 15.5% of 1 repetition maximum (1RM) and the other leg a heavy resistance exercise (HE) load at 70% of 1RM.Methods. In the overnight fasted state a primed, continuous infusion of 1‐13C‐leucine was initiated. Before exercise intervention with LE and HE intensities resting biopsies were obtained from vastus lateralis (VL) muscle. At 0:30, 3:00, and 5:30h post exercise biopsies were taken bilaterally from VL.Results. LE resulted in a moderate elevation in FSR (0.11±0.01%/h, P<.05) in the early post exercise phase (0:30‐3h), and decreased thereafter towards basal values. The HE resulted in a marked increase in FSR only in the late phase (3–5:30h) after exercise (0.13±0.02%/h) compared to rest (P<.01), early HE (P<.05), and late LE (P<.10). The s6kinase(t421/s424) was markedly hyper‐phosphorylated (h‐phos) in HE at 0:30h compared with rest and LE (P<.001). The 4E‐BP1(t37/46) was h‐phos weakly in LE at 0:30h but markedly (P<.01) h‐phos following HE at 3:00h compared with rest and 0:30h.Discussion. The temporal changes in myofibrillar FSR following LE and HE seem to be more related to the h‐phos of 4E‐BP1(t37/46) than to the s6kinase(t421/s424).
Peroxiredoxin 1 is Upregulated by Laminar Shear Stress via Nrf2 Transcription Factor
Authors: Mowbray Amy Leigh , Chen Xi‐Lin , Kang Sang Won , Rhee Sue Goo , Jo Hanjoong 
Published: June 2021

Endothelial cells (EC) exposed to oscillatory shear stress (OS) experience oxidative stress as a signature of atherosclerosis. Conversely, unidirectional laminar shear stress (LS) reduces reactive oxygen species (ROS) production and subsequent inflammatory responses. LS induces many protective genes via a shear‐sensitive antioxidant response element (ARE). We showed that the antioxidant enzyme peroxiredoxin 1 (PRX 1) is upregulated intracellularly by chronic LS, compared to OS and static (ST) culture. In addition, PRX 1‐knockdown attenuated LS‐dependent ROS reduction in EC. We hypothesize that shear‐dependent PRX 1 expression is regulated by ARE through the transcription factor nuclear factor (erythroid‐derived 2)‐related factor 2 (Nrf2). Quantitative, real‐time PCR indicated that chronic LS increased PRX 1 mRNA, compared to OS and ST. Immunoblots also showed increased PRX 1 protein expression in response to Nrf2 adenovirus infection of EC. These results indicate that shear‐dependent PRX 1 expression is regulated at the transcriptional level, and Nrf2 may play an important role in this mechanism. Through this pathway, PRX 1 acts as a mechanosensitive antioxidant implementing anti‐inflammatory and anti‐atherogenic effects of shear stress.Supported by NIH HL71014, HL75209, and HL70531 (HJ), Korean Ministry of Science & Technology FPR05C2‐510 (SWK), and AHA pre‐doctoral fellowship (ALM).
Conditional Overexpression of Cardiac‐Specific PI3Kα Improves Basal Myocardial Function
Authors: Yano Naohiro , Zhao Ting C , Tseng Andy , Padbury James F , Tseng Yi‐Tang 
Published: June 2021

We have shown that PI3K signaling is highly regulated during cardiac development with the highest levels found during the fetal‐neonatal transition period and the lowest in adult. Transgenic models have established overexpression of the PI3K signaling results in increased organ size. The effects on proliferation, however, have not been carefully examined in vivo. To study the effects of PI3K on cardiomyocyte proliferation, we have engineered a tet‐off conditional transgenic mouse model to control the overexpression of cardiac‐specific PI3Kα. Newborn and adult transgenic mice were allowed to overexpress PI3Kα for two weeks and cell proliferation and basal myocardial functions were assessed, respectively. Basal cardiac function was assessed with the Langendorff perfusion system. Cell proliferation was measured with Ki‐67/troponin T double‐labeling immunohistochemistry.Overexpression of cardiac PI3Kα, Akt and p70S6K was confirmed and was associated with an increase in cyclin D1 but not cyclin D3 levels. Adult transgenic mice had better myocardial performance including LV developed pressure, LV dP/dt max and LV dP/dt min. Heart rate and heart/body weight ratio were not changed. Overexpression of PI3Kα was also associated with an increase in cardiomyocyte proliferation in newborns. Hence, cardiac PI3K signaling can be conditionally overexpressed in postnatal stages when there is normally very limited PI3K activity. The new transgenic model can be used to investigate the mechanisms underlying regulation of cardiomyocyte proliferation during development and cardiac remodeling following injury. (NIH 1 P20 RR018728)
An HDL‐mimetic peptide improves cardiac performance and lipoprotein profiles in septic rodents
Authors: Zhang Zhenghao , Miller Andrew P , Zhang Yun , Palgunachari Mayakonda N , Anantharamaiah G.M. , White C. Roger 
Published: June 2021

Background: Cardiac failure is a common cause of death in septic patients, and elevating plasma HDL reduces sepsis complications.Objective: We tested the hypothesis that the apoA‐I mimetic peptide L‐4F improves cardiac function in rats undergoing cecal ligation and puncture (CLP).Methods: Male Sprague‐Dawley rats were randomized to undergo CLP or sham surgery. CLP rats were further subdivided to receive saline (n=11) or L‐4F (10mg/kg, n=12) by ip. injection 6 hours after sepsis induction. Sham‐operated rats received saline (n=8).Results: There was a significant decrease in right atrial pressure, left ventricular end‐diastolic volume, stroke volume and cardiac output 24hrs after CLP. L‐4F blunted changes in these parameters in CLP rats and improved ejection fraction. Lipoprotein profiles were altered by CLP surgery after 24 hrs. Total cholesterol (TC) was reduced from 96± 4 to 51± 4 mg/dl in CLP rats and was principally characterized by a reduction in HDL (80± 3 to 23± 3). L4F administration to CLP rats attenuated this shift in lipoproteins (TC: 67± 5/HDL: 43± 3).Conclusion: L‐4F treatment improved cardiac performance in CLP rats compared to saline‐treated controls. This was associated with an increase in HDL cholesterol and a decrease in plasma and cardiac cytokines. It is hypothesized that HDL reduces sepsis complications by neutralizing pathogens, such as endotoxin, in CLP rats. Supported by NIH DK070040.
Heart – Kidney Connection: Myocardial Infarction Induces Widespread Changes in Renal Cortical and Medullary Gene Expression together with Cortical and Medullary Fibrosis
Authors: Martin Fernando L , Huntley Brenda K , Harders Gerald E , Sandberg Sharon M , Heublein Denise M , Burnett John C 
Published: June 2021

Studies in human myocardial infarction (MI) suggest that even in the absence of heart failure (HF) alterations in renal function may occur and contribute to poor outcomes. We hypothesized that even without preexisting renal disease, renal functional, structural and molecular changes would be present following MI.Wistar rats were used, Sham(S;n=10) and MI(n=9). 3 weeks after MI, GFR was determined by inulin clearance. Blood was obtained for PRA and aldosterone. Cardiac function was assessed by echo. Genomewide microarray analysis was performed on kidney cortex (KC) and medulla (KM) (Affymetrix). EF decreased after MI (S:63±2, MI:43±6%, p<0.01) and LVEDd increased. PRA, aldosterone and blood pressure (BP) did not change. There was no HF as Na and water excretion was maintained. GFR tended to decrease. Pic Red staining in the KC and KM after MI showed greater fibrosis (KC S:1±0.2, MI:3±0.6%, p<0.001 and KM S:1±0.2, MI:19±6%, p<0.005). Microarray analysis showed that 303 genes changed in KM and 407 genes in KC after MI (1.5 fold, P<0.05) related to structure morphogenesis and metabolic processes(Z value>2). We conclude that experimental MI results in renal structural remodeling characterized by cortical and medullary fibrosis with a mild reduction in GFR and extensive modulation of molecular pathways related to renal growth and morphogenesis underscoring a heart‐kidney connection after MI.
Duration of ventricular fibrillation affects first post‐shock activation time and defibrillation threshold
Authors: Dosdall Derek James , Osorio Jose , Robichaux Robert , Huang Jian , Ideker Raymond E 
Published: June 2021

Background: Defibrillation waveforms and strategies have been developed using models of short duration ventricular fibrillation (SDVF). Significant metabolic changes occur after long duration ventricular fibrillation (LDVF) that may play an important role in the mechanisms of defibrillation. The objective of this study was to determine if defibrillation threshold (DFT) or the time to 1st post‐shock activation (PSA) differed after SDVF and LDVF.Methods: A ramp up protocol was used to determine the defibrillation threshold (DFT) of a biphasic waveform in 9 pigs (30–35 kg) and 6 beagles (9–11 kg) after one episode each of SDVF (10 s) and LDVF (150 s). PSA time was recorded by intraventricular catheters in the both ventricles after successful defibrillation shocks.Results: The DFT was higher for pigs after SDVF than LDVF (102±43 J and 79±34, respectively, p<0.05) but was not significantly different for beagles (8.3±1.5 and 13.3±9.3 J, respectively). The majority of the PSA after SDVF were recorded within 170 ms of the shock, (9/9 pigs, 4/6 beagles), while all PSAs after LDVF had a pause of greater than 275 ms.Conclusion: Different times of PSA and a change in DFT in pigs may indicate that there are significant differences in defibrillation after SDVF and LDVF. Further study of defibrillation after LDVF is warranted to determine if strategies and waveforms may be improved for clinically relevant durations of LDVF.
Characterization of Pokeweed Antiviral Protein's interaction with eukaryotic initiation factors and an S/R loop oligo
Authors: Friedland Diana Elaine , Goss Dixie J. , DeGrazia Jeannine , Baldwin Amy E. 
Published: June 2021

Plant viruses have numerous invasion strategies thus plants have devised ways to continuously defend themselves against pathogenic attack. Ribosome‐inactivating proteins (RIPs) are naturally occurring cytotoxic N‐glycosidase agents and are found in numerous species. They inhibit protein synthesis by depurinating A4324 on the conserved sarcin/ricin loop (SRL) of the 28S rRNA. Pokeweed Antiviral Protein (PAP) is a type I RIP that has long been recognized as an antiviral agent. It is also able to inhibit infection without loss of host cell translation.Here we report in vitro fluorescence studies of PAP‐eIFiso4G binding revealing an interaction with a Kd of approximately 100 nM. This interaction enhances the cap binding affinity of PAP 3‐fold. Our experiments have shown that PAP binds to cap with a similar affinity to that of the wheat germ cap binding protein eIFiso4E. ATP and GTP compete with cap for PAP binding; both nucleotides and the cap analog show little salt dependence in binding, suggesting that the interactions are specific for these nucleotides. Binding to an oligonucleotide that contains the S/R sequence was slightly weaker than cap binding. We have also determined that PAP directly interacts with eIFiso4E. The biological significance of PAP‐cap binding remains unclear, however this may serve as a means to target RNA or, since ATP binds to the same site, this may be a protective mechanism for host cell capped RNA. The interaction with initiation factors suggests that additional proteins may aid PAP in accessing particular RNA and distinguishing structural elements of the RNA.This work was supported in part by a Research Opportunity Award (NSF MCB 0413982 and a CUNY Collaborative Incentive Research Grant 80209‐07‐12).
The URE2 IRES of yeast: physical characterization and regulation by eIF2A
Authors: Merrick William C. , Reineke Lucas C. , Cao Yu , Caprara Mark G. 
Published: June 2021

Previous studies established that the cellular URE2 mRNA contains an IRES element in the region encoding the N‐terminus of Ure2p. We have determined the minimal IRES element for this mRNA. It is a stem of about 10 base pairs and with a loop of about 24 nucleotides. The size of the loop is a determinant of efficiency with smaller loops leading to reduced levels of expression. To date, all mutations that increase the stability of the stem reduce the level of expression. At the same time, limited mutations that destabilize the stem also show reduced expression. Thus, it would appear that an optimal balance of stability has been selected naturally in yeast.All of the IRES constructs tested are effectively repressed by eIF2A. We conclude that the regulation by eIF2A is not due to any cis‐acting element in the mRNA, but rather to the process of internal initiation. We are currently attempting to determine if there are trans‐acting factors that influence the expression from the URE2 IRES element or other portions of the URE2 mRNA that enhance or repress IRES‐mediated expression. The regulation of eIF2A is also being examined. Studies of the eIF2A mRNA indicate that most/all stresses lead to a dramatic reduction in eIF2A mRNA levels. However, we do not see uniform reductions in eIF2A protein and are currently evaluating whether post‐translational modifications may be associated with those circumstances. (NIH GM068079 and T32 GM08056)
Post‐natal age enhances somal calcium responses of peripheral chemoreceptor neurons in response to extracellular ATP
Authors: Nunes Ana Rita , Gauda Estelle B. , Donnelly David F 
Published: June 2021

ATP, acting through P2X receptors, mediates hypoxia‐induced excitation in the carotid body (CB). The magnitude of excitation increases over the first 3 weeks after birth. We hypothesized that this increase is due, in part, to enhanced responses of P2X receptors. The CB was harvested, intact, with the petrosal ganglion and chemoreceptor neurons of SD rats aged P12‐P17 (n=5, younger) and P20‐24 (n=2, older). Chemoreceptor neurons were labelled by applying calcium green dextran crystals (3 Kd, Molecular Probes) to the CB. The change in fluorescent (°F) from baseline in response to increasing concentrations of ATP was obtained for 57 and 36 neurons in the younger and older animals, respectively. At each concentration of ATP, the percent of positively responding cells was greater for the older than the younger animals: 45% vs 30% at 250 μM; 67% vs 21% at 500 μM; and 34% vs 6% at 1000 μM of ATP. Furthermore, the magnitude °F was greater in the older vs the younger animals with 11 vs 5% of the cells, having > 20% °F in response to 500 μM of ATP and 11 vs 3% in response to 1000 μM of ATP in the older vs younger age group, respectively. The °F in response to ATP was blocked by pre‐incubation with suramin (0.1 μM) nonspecific blocker, or TNP‐ATP (0.5 μM ) PX3 receptor blocker. Thus, a greater sensitivity of the P2X receptors on chemoafferents to ATP may in part account for maturation of hypoxic chemosensitivty.NIH HL072748; SFRH / BD / 39473 / 2007
Potential Role of a Thiol Oxidation‐Elicited Subunit Dimerization Activation of Protein Kinase G in the Relaxation of Pulmonary Arteries to Hydrogen Peroxide
Authors: Neo Boon Hwa , Kandhi Sharath , Wolin Michael 
Published: June 2021

We have previously provided evidence that hydrogen peroxide (H2O2) stimulates soluble guanylate cyclase under conditions where it relaxes isolated endothelium‐removed bovine pulmonary arteries (BPA). Since it was recently reported that H2O2 induces coronary vasorelaxation associated with a NO/cGMP‐independent thiol oxidation/subunit dimerization activation of protein kinase G, we investigated if this mechanism participates in the relaxation of BPA to H2O2. BPA precontracted with serotonin (incubated under hypoxia to lower endogenous H2O2) were exposed to increasing concentrations of H2O2. It was observed that 0.1‐1 mM H2O2 caused increased PKG dimerization and relaxation. These responses were associated with increased phosphorylation of vasodilator‐stimulated phosphoprotein (VASP) at the serine‐239 site known to be mediated by PKG. Treatment of BPA with 1 mM dithiothreitol attenuated PKG dimerization, VASP phosphorylation and relaxation to H2O2. Thus, a thiol oxidation‐elicited dimerization activation of PKG appears to be a contributing factor to the relaxation of BPA to H2O2.Supported by NIH grants HL31069, HL43023 and HL66331