bluuebunny/crossref_metadata_2025_split huggingface dataset:
Placental growth factor (PlGF) is a potent dilator of uterine and mesenteric veins isolated from pregnant rats
Authors: Mandala Maurizio , Kostin Shannon , Osol George 
Published: June 2021

PlGF, a member of the VEGF family, is produced by the placenta; impairment of its signalling has been reported in preeclampsia. We tested the effect of PlGF on uterine and mesenteric veins to evaluate its vasoactive properties in reproductive vs. non‐reproductive tissues. Uterine (pre‐myometrial, pre‐placental) and third order mesenteric veins isolated from pregnant rats (n=12) were cannulated and pressurized (6 mmHg) in an arteriograph. All vessels were preconstricted 40–50% with U46619 prior to being exposed to PlGF (10pM–3nM). PlGF produced vasodilation in a concentration‐dependent manner in all veins. Similar maximal relaxations were observed in pre‐myometrial (32 ± 5%) and pre‐placental (36 ± 10%) veins, while greater efficacy (52 ± 10%, p<0.05) was noted in mesenteric veins. The kinetics of the vasodilatory response were also different, with half times on the order of 20 vs. 10 minutes in uterine vs. mesenteric vessels. In mesenteric veins, inhibition of NOS + COX reduced vasodilation by 65% on average, to 18 ± 9% (p = 0.03). Thus, PlGF is a potent vasodilator of both reproductive and systemic veins, with significantly more potent and rapid effects in the mesenteric circulation, suggesting an important role for the tissue VEGFR‐1 (Flt‐1) receptor in regulating maternal gestational hemodynamic changes, e.g. venous capacitance and return, and cardiac output.This study was supported by NIH HL79253
SM22α Phosphorylation: A Novel Mechanism of Activation of PKCδ‐P47phox Axis and ROS Production in VSMCs
Authors: Pin Lv , Mei Han 
Published: June 2021

Smooth muscle 22 alpha (SM22α), an actin‐binding protein abundant in vascular smooth muscle cells (VSMCs), is downregulated in atherosclerosis. The recent study indicates that disruption of SM22 promotes arterial inflammation through activation of reactive oxygen species (ROS). However, the molecular mechanisms by which SM22α controls the production of ROS have not been characterized. We investigated the effect of SM22α disruption on ROS production. ROS was detected using dihydroethidium for superoxide. The expression of proteins was detected by Western Blotting after transfection with small interfering RNA. We showed that down‐regulation and phosphorylation of SM22α were associated with angiotensin (Ang) II‐induced increase in ROS production in VSMCs. The phosphorylation of SM22α at Serine 181 was increased in an AT1R‐PKCδ pathway‐dependent manner in VSMCs upon Ang II. Phosphorylated SM22α facilitated Ang II‐inducted ROS production via activation of PKCδ‐p47phox axis through release of PKCδ and actin dynamics in VSMCs and was associated with intimal thickening. These results indicate that disruption of SM22α plays pivot roles in regulation of ROS production in VSMCs, and may be a potential target for the development of new therapeutics for vascular diseases..Source of fundings: This study was supported by the National Natural Science Foundation of China (31071003).
Prostaglandin E2 Activates Basal EP4 Receptors to Stimulate Chloride Secretion Via Both cAMP and Calcium Mediated Pathways
Authors: Rajagopal Madhumitha , Kathpalia Paru P , Pao Alan C. 
Published: June 2021

The renal collecting duct (CD) maintains salt (NaCl) balance by fine‐tuning NaCl excretion in response to dietary salt intake. Under conditions of high dietary salt intake (HDS), prostaglandin‐E2 (PGE‐2) production is enhanced and promotes NaCl excretion. The molecular mechanisms by which PGE‐2 works are not well defined. Under conditions of HDS, Na+ reabsorption is suppressed, and the regulation of Cl− secretion may predominate. The initial segment of the inner medullary CD (IMCD) is the only segment known to secrete Cl− under HDS. We used the mIMCD‐K2 cell line, a mouse cell line derived from the initial IMCD, to study the effects of PGE‐2 on Cl− transport in the IMCD.In mIMCD‐K2 cells, PGE‐2 activates basolateral EP‐4 receptors (EP‐4R) to increase Cl− secretion via both the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Ca2+ activated Cl− channels (CACC). EP‐4R activation enhances cAMP production which activates CFTR; unexpectedly, we found that EP4R activation also increases intracellular Ca2+ to stimulate CACC mediated Cl− secretion. We also determined that PGE‐2 stimulated secretion involves crosstalk between cAMP and Ca2+ signaling pathways in which intracellular Ca2+ influences CFTR activity and cAMP influences CACC activity. These two pathways, and the crosstalk between them, may represent a concerted mechanism by which PGE‐2 acts to enhance NaCl excretion under conditions of HDS.
Disordered oxygen metabolism in early chronic kidney disease
Authors: Singh Prabhleen , Pham Hai , Sharik Meaghen , Murphy Anne , Petrosyan Susanna , Thomson Scott , Blantz Roland 
Published: June 2021

Structural changes leading to chronic renal hypoxia, implicated in chronic kidney disease (CKD) progression, occur late and do not explain early intrarenal hypoxia. To examine the early functional adaptations that may increase oxygen demand leading to hypoxia, micropuncture and oxygen consumption (QO2) studies were conducted in rats 1 week after subtotal nephrectomy (STN).Although, oxygen delivery (DO2) was lower in STN, renal oxygen extraction (arterial‐venous O2 content) doubled in STN vs. control (0.014 vs. 0.007, p<0.05). Both QO2 and (A‐V)O2 factored for GFR were significantly higher in STN. Single nephron GFR nearly doubled in STN vs. controls (p<0.05) contributing to transport related QO2 but could not explain the 3‐fold increase in QO2/nephron. Proximal reabsorption was lower in STN shifting salt reabsorption to distal sites associated with increased energetic costs. Expression of NADPH oxidase was also increased in STN. Mitochondrial QO2 revealed lower state3 respiratory capacity and respiratory control ratio (RCR) in STN, suggestive of mitochondrial complex I dysfunction seen in hypoxia. Treatment with hypoxia inducible factor (HIF) inducer, DMOG, significantly improved several parameters (p<0.05) including DO2, (A‐V)O2,(A‐V)O2/GFR, and mitochondrial state3respiratory capacity and RCR in STN. Major alterations in both mitochondrial and non‐mitochondrial QO2 in early STN, most of which were corrected with HIF induction.
Hypoxia induced subunit switching on cytochrome c oxidase in sleep apnoea patients
Authors: Schiffer Tomas , Larsen Filip J , Lundberg Jon , Weitzberg Eddie 
Published: June 2021

Obstructive sleep apnoea syndrome (OSAS) is characterized by nocturnal arterial desaturation with sustained hypertension and increased oxidative stress. For unknown reasons, exercise capacity is reduced and resting metabolic rate is increased in OSAS patients. Mitochondrial cytochrome c oxidase (COX) has emerged as a regulator of respiratory control and cell studies indicate that subunits of COX can switch between different isoforms in response to changes in oxygen availability.ObjectiveTo study intrinsic changes in the nuclear subunit composition and kinetic properties of COX in OSAS patients compared to a control group.MethodsSkeletal muscle biopsies were taken from tibialis anterior. Subunit composition was quantified by western blotting and intrinsic activity of COX was measured spectrophotometrically in the presence and absence of an ATP‐regenerating system.ResultsTotal citrate synthase, COX1 content and COX activity were unchanged in the OSAS patients, indicating unaltered overall mitochondrial biogenesis. In contrast increased expression of COX IV‐2 was found (P<0.05) along with a trend of increased COX IV‐ 1 (P= 0.11). The mitochondrial protease LON responsible for the degradation of COX IV‐1 trended to decrease (P=0.09).ConlusionPatients with OSAS exhibit a switch in COX subunits and levels of LON as a result of intermittent nocturnal hypoxia.
Experimental spinal cord injury alters the dose response of vagal motoneurons to TRH
Authors: Holmes Gregory M , Swartz Emily M 
Published: June 2021

Spinal cord injury (SCI) elicits immediate and profound gastric dysmotility. The stomach is modulated by gastric sensory signals transmitted via the vagus nerve to the nucleus tractus solitarius (NTS). The NTS integrates sensory information with signals from throughout the CNS and projects to nuclei which include preganglionic efferent neurons located in the dorsal motor nucleus of the vagus (DMV).This vago‐vagal reflex remains anatomically intact after SCI and our previous reports suggest that SCI diminishes vagal afferent sensitivity. However, derangements in efferent signals to the stomach may also account for reduced motility. Thyrotropin releasing hormone (TRH) profoundly modulates gastric motility by a direct depolarization of DMV neurons and offers a pharmacological tool to test DMV efferent integrity.We tested the hypothesis that experimental SCI induces functional impairment of rat DMV motoneurons by microinjecting TRH into the DMV 3 days after SCI or control surgery.Our data reveal a rightward dose‐response shift to unilateral DMV microinjection of TRH (0, 3, 10, 30 or 100 pmoles, n=40 total). Specifically, gastric motility response to 3pmoles TRH was reduced in SCI animals vs. surgical controls.Combined with our previous reports, these data suggest that SCI may also impair vagal preganglionic motoneurons. The mechanism leading to this impairment remains to be determined.
Ventilatory chemoreflex enhancement in cigarette smokers is reversed by ascorbic acid
Authors: Leuenberger Urs A. , Vazquez Robert , Drew Rachel C. , Muller Matthew D. , Sauder Charity , Blaha Cheryl , Mast Jessica 
Published: June 2021

Cigarette smoking causes oxidative stress in humans. Furthermore, in animal models carotid chemoreceptor afferent activity is enhanced by reactive oxygen species and attenuated by antioxidant interventions. To test the hypothesis that chemoreflex control is altered in cigarette smokers and is normalized with an antioxidant, we determined the hemodynamic, ventilatory and sympathetic (peroneal microneurography) responses to transient hypoxia (2–8 breaths of 100% N2), hyperoxia (100% O2, 5 min), and fatiguing static handgrip exercise before and following intravenous infusion of ascorbic acid (60 mg/kg) in cigarette smokers free of overt cardiovascular disease (age 45±4 yrs, body‐mass‐ index 26±2 kg/m2). Compared to a non‐smoking control group (n=11), in smokers the ventilatory responses to transient hypoxia (i.e., the ventilatory chemoreflex slopes) were enhanced (P<0.05, n=11). Importantly, these responses were partly normalized by ascorbic acid (pre vs. post: 0.58±0.08 vs. 0.45±0.06 L/min/% O2 desaturation; P<0.05). In contrast, ascorbic acid did not affect the neurocirculatory responses to hyperoxia (P=NS, n=10) or static handgrip exercise (P=NS, n=7). These data suggest that in cigarette smokers oxidative stress contributes to chemoreflex dysfunction.Supported by P01 HL077670 and UL1 RR033184.
Intrarenal and sympathetic premotor neuron changes in response to denervation of ischemic kidney in renovascular hypertension
Authors: Nishi Erika Emy , Bergamaschi Cassia T , Gomes Guiomar N , Perry Juliana C , Naffah-Mazzacoratti Maria G , Castro Eduardo F , Campos Ruy R 
Published: June 2021

AT1R upregulation in the rostral ventrolateral medulla (RVLM) contributes to sympathoexcitation and arterial hypertension in the 2‐kidney,1‐clip (2K1C) model. Our aim was to investigate whether afferent and efferent renal sympathetic nerves play a role in the modulation of Ang II receptors expression in the central nuclei (RVLM and PVN) and renal lesion markers in renovascular hypertension. Renal denervation of clipped kidneys (DnX: visible bundles were dissected + 10% phenol) was performed in Wistar male rats (n=5/group) 4.5 weeks after clipping. Ten days after DnX the mean arterial pressure was significantly (p<.05) reduced (202 ± 6 vs 178 ± 9 mmHg) in the 2K1C rats. The AT1R was upregulated in the RVLM (73%) and PVN (43%) in the 2K1C group, DnX normalized these expressions in both nuclei. The AT2R expression was increased in the RVLM (76%) and PVN (76%) of 2K1C group and DnX reduced AT2R in both regions. Renal lesion was characterized by cortical interstitium α‐smooth muscle actin (α‐SMA) immunohistochemical expression. The α‐SMA expression was augmented in the clipped (67 fold) and nonclipped (127 fold) kidneys and DnX significantly reduced α‐SMA in both kidneys (9 and 25 fold, respectively) of 2K1C rats. DnX produced no changes in control rats. Thus, our data show that renal nerves may modulate Ang II receptors in the RVLM and PVN and contribute to renal lesion in the renovascular hypertension.Supported by FAPESP and CNPQ
Inhibition of brain endoplasmic reticulum (ER) stress attenuates hypertension in diet‐induced obesity (DIO)
Authors: Mark Allyn L , Young Colin N , Butler Scott D , Guruju Mallikarjuna , Davisson Robin L 
Published: June 2021

ER stress in brain metabolic centers has been implicated in the pathogenesis of obesity‐hypertension, independent of effects on metabolic pathways. We recently reported molecular and ultrastructural evidence for DIO‐mediated activation of ER stress in key brain cardiovascular control regions. We tested the hypothesis that inhibition of brain ER stress with the chemical ER chaperone TUDCA attenuates obesity‐hypertension. Adult male C57Bl/6 mice were fed a high fat (HFD, n=8) or control (CON, n=6) diet for 21 wks. Mice were then implanted with radiotelemeters and intracerebroventricular (ICV) cannulae and allowed 1 wk recovery. DIO mice had elevated MAP (121±1 vs 112±1 mmHg; P<0.05) and white adipose tissue (1.67±0.01 vs 0.59±0.09 g; P<0.05) and liver weights (1.77±0.18 vs 1.27±0.04 g; P<0.05) compared to CON. ICV TUDCA (5 μg/day, 3 days) decreased MAP in DIO mice compared to ICV vehicle (115±2 vs 120±1 mmHg; P<0.05), whereas it had no effect on MAP in CON mice (TUDCA, 113±3 vs Vehicle, 114±1 mmHg; P>0.05). ICV TUDCA also decreased body (−5.1±1.2 g vs 0.1±1.0 g; P<0.05) and liver weights (1.19±0.08 vs 1.77±0.18g; P<0.05) compared to vehicle, but had no effect on white adipose tissue mass (1.71±0.29 vs 1.67±0.01 g; P>0.05). These data suggest that inhibition of brain ER stress attenuates hypertension and hepatic enlargement but not white adipose tissue mass in DIO mice.HL063887, HL084207
Positive correlation between cyber leisure time and sympathetic activity in high school students
Authors: Son Mi Eun , Kim Na-Hyun , Kong In Deok 
Published: June 2021

PurposeThe purpose of this research was to find out the relationship between cyber leisure time and autonomic nerve system in high school students.MethodsThe subjects of this study were 262 second graders at high school located in D city. The research design was descriptive correlation study. Data were collected from August 26 to September 17, 2010, using cyber leisure questionnaire and heart rate variability by SA‐6000 for autonomic balance.ResultsTotal time for the cyber leisure was 385.8±261.7 (min/week). Time for internet search and computer game was 230.0±139.7 (min/week) and 155.8±163.1 (min/week), respectively. There were significant positive correlation between cyber leisure time and sympathetic activities (r=.13, p<.05).ConclusionThe use of the internet and computer game could potentiate sympathetic activities in high school students. Thus, nursing intervention to reduce the total cyber leisure time will be helpful to improve physical, physiological, and psychosocial health for them.
Two nerve morphometry methods performed through the same computer program: are they comparable?
Authors: da Costa Bilego Neto Antônio Paulo , Silveira Fernando Braga Cassiano , Sanada Luciana Sayuri , Fazan Valéria Paula Sassoli 
Published: June 2021

Morphometry has been widely used in studies designed to establish normal patterns of biological structures or to compare changes resulting from pathological processes. It can be performed manually or through semi‐automatic or automatic methods. However, it is difficult to compare results between studies that used different methods. We aimed to compare the results of two different methods of nerve morphometry, automatic and semi‐automatic, using the same computer software. Female Wistar rats (n = 5) with 90 days of age had their right and left sural nerves prepared for light microscopy. Automatic and semi‐automatic morphometry was performed using the program KS‐400 and took into consideration: area and lesser diameter of myelinated fibers and their axons, the myelin sheath area and the ratio between the lesser diameter of the axon and its respective myelinated fiber (G‐ratio). The nerves are longitudinally and laterally symmetric with both morphometric methods. A significant overestimation of the myelinated fibers size and a significant underestimation of the myelinated axons size were observed with the automatic method. Our results indicate an important differences in the values of the myelinated fibers morphometry of one nerve, obtained with two different methodologies. Thus, the same methodology must be standardized and used throughout a single experiment.Grant Funding Source : FAPESP, CNPq and FAEPA
Ultrastructural investigation of the aortic depressor nerve in Wistar and Wistar‐Kyoto rats
Authors: de Amorim Milena Menezes , da Silva Letícia Oliveira Neri , de Aguiar Mendes Vânia Alice , Salgado Helio Cesar , Fazan Valéria Paula Sassoli 
Published: June 2021

Ultrastructural study of the aortic depressor nerve (ADN) [1] showed differences on the morphology and morphometry between normotensive Wistar‐Kyoto (WKY) and spontaneously hypertensive rats (SHR), particularly in the number of unmyelinated fibers. The aim of the present study was to investigate if there are ultrastructural differences on the AND of two different normotensive rats strains. Twelve Wistar rats (WR) and 13 WKY had their left ADN fixed in 2,5% glutaraldehyde. Thin cross sections of proximal and distal segments of the ADN were studied by transmission electron microscopy and a morphometric study of the unmyelinated fibers was performed. Comparison between proximal and distal segments of the two strains revealed a longitudinal symmetry. Comparison between strains revealed that, despite the fact that WR are heavier (body weight = 339 ± 17g for WR and 277 ± 54 for WKY) than WKY, ADN unmyelinated fiber number and size is significantly larger in WKY. Unmyelinated fiber distribution is unimodal in both segments for both strains but WKY distribution was skewed to the right with a high percentage of fibers larger than 1.5 μm. Average values of unmyelinated fibers morphometric parameters are higher in WKY due to a larger number of fibers bigger than 1.5 μm.Grant Funding Source: FAPESP, CNPQ, CAPES and FAEPA
A new regulatory pathway of mRNA export by an F‐box protein, Mdm30
Authors: Durairaj Geetha , Bhaumik Sukesh R. 
Published: June 2021

Regulatory role of ubiquitylation has been implicated in various steps of gene expression and mRNA export is not an exception. Specificity of this modification is conferred by E3 ligases whose function is dictated by specific domains they possess. Role of HECT domain containing E3 ligases like Tom1 and Rsp5 have previously been implicated in regulation of mRNA export. However, pertaining to diversity of E3 ligases, the roles of other ligases in this aspect of gene expression is unknown. Interestingly, our recent work established the role of an F‐box protein, Mdm30, in stimulation of mRNA export. F‐box proteins are bonafide members of RING domain containing SCF (Skp1‐Cullin‐F box) ligase complex. To elucidate the mechanism‐of‐action of Mdm30, we carried out a series of experiments. We find that Mdm30 ubiquitylates the Sub2 component of Transcription/Export complex (TREX) in SCF dependent manner. Ubiquitylated‐Sub2 is subsequently degraded by 26S proteasome complex. Such targeted degradation of Sub2 enhances the recruitment of mRNA export adaptor, Yra1, onto active gene to promote mRNA export. Collectively, these results provide a new regulatory pathway of mRNA export, and will be presented in this conference.Funding: Excellence in Academic Medicine (EAM) from the School of Medicine, Southern Illinois University.
CAP INDEPENDENT TRANSLATION CONTROLS IN BARLEY YELLOW DWARF VIRUS (BYDV)
Authors: Banerjee Bidisha , Sharma Sohani Das , Goss Dixie J. 
Published: June 2021

BYDV has economic importance because it infects a broad range of cereal crops and can severely limit food grain production. Little is currently known about the mechanism of cap‐independent translation (CIT), an alternate means employed by many plant viruses e.g. BYDV to circumvent host defense mechanisms. Protein‐RNA complexes formed during the translation processes are dynamic and binding/release kinetics influence the sequential assembly of the initiation complex.The CIT mechanism was investigated by studying the role of eukaryotic initiation factors (eIF) eIF4F, eIF4B, eIF4A and PABP in the translation initiation complex formation using the biophysical techniques fluorescence anisotropy and stopped flow kinetics. BYDV translation element (BTE) located in 3’ UTR (Untranslated RNA) of mRNA and a non‐functional mutant BTEBF bound eIF4F with equal binding affinity (Kd). The presence of other eIFs had a negligible effect on the equilibrium binding of eIF4F to BTE/BTEBF RNA. Recently obtained data indicate that the BTE (first order rate constant kobs= 12.3±0.2 sec−1) bound eIF4F three times faster than the un‐translating BTEBF (kobs= 4.4+0.5 sec−1) suggesting that kinetics play a role in the translation of these RNAs.
MOLECULAR BASIS OF RNA POLYMERASE II TRANSCRIPTION FIDELITY
Authors: Wang Dong 
Published: June 2021

A long‐standing key question in the transcription field has been how Pol II achieves such a high transcriptional fidelity, with an error rate ranging between 10‐4 and 10‐5.Maintaining transcriptional fidelity is vital to cells and organisms. Novel insights into this subject have recently emerged from a combination of structural, genetic and biochemical studies, suggesting that the high accuracy of Pol II transcription is achieved by specific nucleotide selection and by removal of misincorporated nucleotides (proofreading). Here, we use a combined approach including pre‐steady state transient kinetics, X‐ray crystallography, and molecular dynamics simulations to elucidate the chemical principles in controlling Pol II transcription fidelity.
Synergy Between Chromatin Remodeling Complexes and pre‐mRNA Splicing
Authors: Pradhan Suman Kalyan , Soule Erik , Johnson Tracy L 
Published: June 2021

Pre‐messenger RNA splicing plays a critical role in gene expression. In spite of the considerable progress that has been made in understanding the mechanism of splicing, an important question that remains poorly understood is how changes in the chromatin template affect splicing. Observations of enriched nucleosome occupancy and histone modifications in the exonic regions of genes raise the possibility that specific histone marks may be associated with splicing signals. For example, proteins that bind to methylated histones facilitate the recruitment of snRNPs to nascent transcript and influence the efficiency of splicing. Recently, we have shown that GCN5‐dependent histone acetylation is critical for cotranscriptional spliceosome assembly and its rearrangements. To gain further mechanistic insights, we have explored the possibility of communication between the chromatin remodeling machinery that interact with acetylated histones and the splicing machinery. Genetic analyses have identified functional interactions between components of chromatin remodeling complexes and components of the U2 snRNP. Furthermore, in vivo interaction studies demonstrate physical interactions between the Swi/Snf complex and the U2 snRNP. Together, these studies suggest a synergistic relationship between the Swi/Snf complex and the splicing machinery in gene expression.Funding: NIGMS (GM085474 and GM085764)