bluuebunny/crossref_metadata_2025_split huggingface dataset:
S1P1 receptor activation is insufficient to mimic S1P‐mediated effects on aqueous humor outflow physiology
Authors: Sumida Grant , Stamer W. Daniel 
Published: June 2021

Previously, sphingosine‐1‐phosphate (S1P) had been shown to decrease outflow facility in human eye organ‐culture models. The aim of this study is to determine the contribution of the S1P1 receptor in the tissues of the aqueous humor outflow pathway in mediating S1P's effect on outflow facility in humans.Post‐mortem human eyes in organ culture were perfused at 8 mmHg constant pressure to obtain a baseline outflow facility. Normalized facilities following the exchange of anterior chamber contents with 5 μM SEW2871 (S1P1 agonist) or vehicle were 1.01 ± 0.10 and 1.05 ± 0.10, respectively (mean normalized facility ± SD; p=0.65). As a control, all eyes responded with a decreased facility following S1P exchange at the end of each experiment. In primary lines of trabecular meshwork and Schlemm's canal cells, the cell types located at the site of outflow resistance, SEW2871 failed to promote MLC phosphorylation (MLC‐P). Interestingly, W146 (S1P1 antagonist) enhanced S1P‐mediated MLC‐P.SEW2871 does not replicate the S1P‐induced decrease in outflow facility, nor does it promote MLC‐P in cell culture models; suggesting other S1P receptor subtypes, alone or in combination with S1P1, are responsible for S1P's action on the outflow pathway.Support: NEI (EY17007) and Research to Prevent Blindness Foundation
WAVE proteins mediate ENaC activity
Authors: Karpushev Alexey V , Levchenko Vladislav , Staruschenko Alexander 
Published: June 2021

The epithelial Na+ channel (ENaC) is an essential channel responsible for Na+ reabsorption. Similar to other ion channels, ENaC activity is regulated, in part, by cortical cytoskeleton. Members of the Wiskott‐Aldrich syndrome protein (WASP)/WAVE family (N‐WASP, WASP, and WAVE1, −2, −3 isoforms) activate Arp2/3‐mediated actin polymerization, leading to distinct downstream effects. N‐WASP inducibly binds Arp2/3 in response to Cdc42, whereas WAVE proteins constitutively interact with Arp2/3 and are effectors of Rac1 activity. Coexpression of Rac1 with ENaC markedly increased channel activity, whereas coexpression of Cdc42 failed to change ENaC activity. N‐WASP and all three isoforms of WAVE significantly increase ENaC activity when coexpressed in CHO cells. However, wiskostatin, an inhibitor of N‐WASP did not effect ENaC activity in cells expressing the channel alone and coexpressed with either N‐WASP or WAVE1. Similarly, wiskostatin had no effect on Na+ reabsorption across mpkCCDc14 principal cell monolayers. Immunoblotting demonstrated the presence of WAVE1 and WAVE2 and absence of N‐WASP and WAVE3 in mpkCCDc14 and M‐1 cells. Immunohistochemistry analysis also revealed localization of only WAVE isoforms in the cortical collecting duct in Sprague‐Dawley rat kidneys in vivo. Thus, our findings suggest that WAVE proteins mediate ENaC activity via interaction with Rac1.Supported by AHA and ASN.
Sex‐specific effects of atorvastatin on the blood pressure response to exercise
Authors: Dostaler Edward G , Thompson Paul D , Axtell Robert S , Latchman Peter , Parker Beth A 
Published: June 2021

PurposeTo examine the effect of statin therapy on the blood pressure response to exercise in healthy adults.MethodsSixty eight adults (n=34 men (M) and women (W); ages 23–67) were randomized to atorvastatin 80 mg (A) daily or placebo (P) in a double blind fashion. Systolic, diastolic and mean arterial blood pressure (SBP, DBP and MAP, respectively) were measured every 3 minutes during a graded maximal exercise test with concurrent assessment of oxygen uptake (VO2) pre‐ and post‐6 months of treatment. The slope of the blood pressure response to exercise was calculated as Δ SBP, DBP or MAP/Δ VO2 (as % of VO2max). A repeated‐measures ANOVA with between‐subject factors of gender and drug was used to investigate slopes across time.ResultsThe time*drug* gender interaction was marginally significant (both p = 0.06) for both the SBP and MAP response to exercise. Specifically, A reduced the slope of the pressor response to exercise in W but not M relative to P groups.SummaryThese findings suggest that atorvastatin may reduce the pressor response to exercise in women but not men. Supported by 1R01HL081893‐03.
A Novel Algorithm for Quantifying Multiunit Sympathetic Nerve Activity
Authors: Brockway Marina , Guzman Pilar , Veitenheimer Britta , Kuroki Marcos , Osborn John W 
Published: June 2021

Although methods for long‐term recording of sympathetic nerve activity (SNA) in conscious animals have become available, the poor signal‐to‐noise ratio (SNR) that is characteristic of SNA recordings has limited the use of SNA preparations in understanding the role of neural control of physiological function. A novel software algorithm Multi‐domain Filtering (MDF) for analysis, denoising, and quantification of SNA has been developed. The MDF technique removes nearly all noise and artifact from SNA recordings including myoelectric artifacts, thermal, electrical and other noises while preserving information regarding the underlying SNA. In addition to denoising, the technique includes a rigorous computation of integrated SNA that more accurately reflects neural spike activity and avoids the time lag inherent to commonly used analog filtering techniques. MDF technique has the potential to extend preparation life by substantially improving SNR, particularly at the end of preparation life. It also has the potential to greatly reduce the need for manual review of data to identify noise events and eliminate the need for interventions to assess baseline noise level. MDF technique has proven to be sufficiently robust and computationally efficient that it can be used to automatically post‐process or real‐time process SNA data in a typical laboratory setting.Supported by NIH Grant HL076312 and VivaQuant ™
CXC Chemokines are Not Direct Mitogens for Hepatocytes
Authors: Clarke Callisia N , Sakai Nozomu , Tevar Amit D , Edwards Michael J , Lentsch Alex B 
Published: June 2021

PURPOSECXC chemokines have been implicated as important mediators of liver growth and regeneration after partial hepatectomy by promoting hepatocyte proliferation. Little is known about the way these chemokines mediate hepatocyte proliferation. Here we investigate whether CXC chemokines are direct mitogens for primary hepatocytes in culture.METHODSHepatocytes were isolated from male Balb/c mice and initially plated in Williams media fortified with fetal bovine serum(FBS), distributed onto 96‐well plates and incubated overnight to allow cell adherence. Media was removed and hepatocytes were incubated for 24 hrs in Williams media or HepatoZYME, (a complete media), with or without FBS in the presence of murine CXC chemokine, macrophage inflammatory protein‐2 at 0, 10 or 10,000 ng/ml. Cytotoxicity was determined by LDH release assay and proliferation by DNA incorporation of BrdU.RESULTSWilliams media without FBS resulted in nearly 100% cell death therefore, subsequent experiments were conducted with HepatoZYME (HZ) media. There was no difference in MIP‐2‐induced hepatocyte cytotoxicity between HZ media containing or lacking FBS. However, hepatocyte proliferation induced by MIP‐2 was present only in HZ media containing FBS.CONCLUSIONCXC chemokines are not direct mitogens for hepatocytes, but stimulate hepatocyte proliferation in the presence of serum factors.
Tumor necrosis factor α is involved in the myogenic response of resistance arteries
Authors: Kroetsch Jeffrey Thomas , Lidington Darcy , Bolz Steffen‐Sebastian 
Published: June 2021

The increase in vascular resistance observed in heart failure primarily results from an enhanced myogenic response (MR), the intrinsic property of resistance arteries (RA) to adapt their diameter and hence, resistance, to changes in pressure. We have recently shown that the cytokine tumor necrosis factor α (TNFα) augments the MR by activating sphingosine kinase‐1 (Sk1). We hypothesized that the TNFα‐Sk1 axis also operates under physiological conditions and that TNFα is an integral signaling element underlying the MR. Isolated hamster RA (n=6) were cultured in a pressure myograph for 20hrs prior to functional tests. Elevation of transmural pressure induced a robust MR (80±23% reversal of pressure‐induced distension). The soluble TNFα receptor etanercept (ETAN; 10μg/mL), which sequesters TNFα, abrogated the MR. This result was confirmed in mouse cremaster RA (n=5). Constriction to norepinephrine (NE) and dilation to acetylcholine (ACh) remained unaffected by ETAN. Heat‐inactivated ETAN (n=6) did not affect the MR or NE‐/ACh‐stimulated responses. TNFα increased Erk1/2 phosphorylation, which is tightly linked to Sk1 activation in resistance arteries.Our data suggest that: (i) TNFα is readily available in the artery wall, (ii) its activation is sensitive to changes in transmural pressure and (iii) TNFα is a key element of the signaling pathway that regulates the MR.Funding: NSERC/Heart and Stoke Foundation
Evidence of a circadian rhythm for muscle sympathetic nerve activity in humans
Authors: Cook Jonathan S , Chin‐Sang Stephanie A , Sauder Charity L , Ray Chester A 
Published: June 2021

We previously observed that exogenous melatonin (3 mg) increases muscle sympathetic nerve activity (MSNA) at rest in humans (Cook and Ray, Clin Auton Res 19:303, 2009). Because melatonin exhibits a circadian rhythm in humans by increasing at night, it was hypothesized that MSNA at rest would be greater at night compared to day. Melatonin typically increases 8–10 times over daytime concentrations during the late evening hours. To test this hypothesis, arterial blood pressure, heart rate, calf blood flow and MSNA was measured in 9 healthy subjects (28 ± 1 yr; 5 male, 4 female) while in the prone position. Each subject was tested around noon and 10–12 hr later that evening (day: 11:34 ± 13 min, night: 22:10 ± 5 min). Subjects were instructed not to sleep between the two testing sessions. Contrary to our hypothesis, MSNA at rest was significantly decreased at night compared to day (8 ± 1 vs. 11 ± 2 bursts/min, respectively) (P < 0.05). Calf blood flow, heart rate, and arterial blood pressure were not significantly different at night compared to day (calf blood flow: 3.2 ± 0.3 vs. 2.8 ± 0.5 ml*100 ml−1*min−1, heart rate: 70 ± 4 vs. 66 ± 4 beats/min, arterial blood pressure: 91 ± 2 vs. 87 ± 1 mmHg, respectively). The data indicate that MSNA at rest decreases during the late evening hours suggesting there is diurnal variation in muscle sympathetic nerve activity in humans.Supported by: NIH HL077670 and a NASA Space Grant Fellowship
Changes in cardiovascular response to Six‐minute walk test in some chronic heart failure patients
Authors: Anigbogu Chikodi Nnanyelu , Ajiboye Olufunke 
Published: June 2021

Objective estimates of cardiovascular performance and fitness can be obtained through standardized exercise tests. This study was to evaluate the cardiovascular responses of Nigerian population of adult patients with chronic heart failure (CHF) to the 6‐minute walk test (6MWT).Participants were 15 adult patients with CHF and 30 age‐matched, apparently healthy individuals with no history of cardiovascular disorders. Ethical clearance was secured from the institutional committee and informed consent obtained from the subjects. On the day of exercise, pre‐test cardiovascular parameters – heart rate (HR), respiratory rate and blood pressure (systolic ‐SBP and diastolic ‐DBP) – were taken; after which the subjects went through the standardized procedures of 6MWT. Differences between the pre‐test and post‐test values and percentage differences were computed. For male and female study and control subjects, paired t‐tests were used to evaluate the significance differences between the pre‐test and post‐test mean values of HR, SBP and DBP. After the 6MWT in male patients, there was 9% increase in HR while female patients had an 8.5% increase (P>0.05). The male control subjects had a 13.4% increase while female control subjects had 9% increase (P>0.05). Significant increases were obtained in DBP for male patients, male control subjects and female control subjects. The 6MWT is a safe and simple instrument for demonstrating cardiovascular responses to sub‐maximal exercise in patients with heart disease and will be useful in compromised communities with limited resources.
Angiotensin II Stimulates Thick Ascending Limb Superoxide Production via activation of AT1 Receptors and PKCα‐stimulated NADPH oxidase
Authors: Herrera Marcela , Silva Guillermo B , Garvin Jeffrey L 
Published: June 2021

Angiotensin II (Ang II) stimulates thick ascending limb (TAL) O2− production but the receptor involved and signaling cascade is unknown. In other cells, activation of AT1 receptors (AT1R) results in PKC‐stimulated NADPH oxidase. We hypothesized that Ang II stimulates TAL O2− production via AT1R and PKC‐stimulated NADPH oxidase. In TAL suspensions, 1nM Ang II stimulated O2− production from 0.8 ± 0.2 to 2.0 ± 0.2 nmoles/min/mg (p<0.003). Losartan, an AT1 antagonist (1μM), blocked the effect of Ang II on O2− (0.9 ± 0.3 nmoles/min/mg; p < 0.02 vs. Ang II alone). PD123319, an AT2 antagonist (1μM), had no effect. Apocynin, a NADPH oxidase inhibitor (10μM), blocked the Ang II‐stimulated O2− by 90% (p<0.01). In isolated TALs, Ang II increased PKC activity, as measured by FRET, from 0.2 ± 0.3 to 1.3 ± 0.2 arbitrary units (p<0.02). A PKC inhibitor, Gö6976 (100nM), blocked the Ang II‐stimulated O2− (0.6 ± 0.2 vs. 2.1 ± 0.3 nmoles/min/mg; p<0.008). To investigate which PKC isoform was involved, we measured O2− in tubules expressing dominant‐negative (dn) PKCα or β1. In control TALs, Ang II stimulated O2− from 1.4 ± 0.1 to 3.6 ± 0.5 nmoles/min/mg (p<0.003). In TALs expressing the dn‐PKCα, Ang II failed to stimulate O2−. In tubules expressing the dn‐PKCβ1, Ang II stimulated O2− from 1.8 ± 0.4 to 3.9 ± 0.4 nmoles/min/mg (p<0.002). We conclude that Ang II stimulates TAL O2− production via activation of AT1R and in PKCα‐stimulation of NADPH oxidase.Support: PO1 HL028982
Overexpression of Act1 drives beta‐defensin expression
Authors: Velichko Sharlene , Anderson Johnathon David , Li Olivia , Huang Fei , Wu Reen 
Published: June 2021

Overexpression of Act1 (CIKS) drives the expression of the human beta defensin gene, DEFB4, in a human bronchial epithelial cell line (HBE1). Act1 is an adaptor protein that is known to interact with I‐kappa‐kinases, as well as the interleukin‐17 receptor chain IL17RA, and is a potent activator of NFκB. We have previously shown that induction of DEFB4 by interleukin‐17 is largely NFκB dependent. Using DEFB4 promoter‐reporter constructs, we surprisingly show that induction of DEFB4 by Act1 overexpression is NFκB independent. Furthermore, we show that induction depends primarily on a region of the DEFB4 promoter that is located between −2.2 kb and −1 kb upstream of the transcriptional start site.This research was supported in part by grants from the NIH (HL077902, HL077315, ES00628)
Effects of Ziram on Humman Natural Killer Cell MAP Kinases and Cytolytic Proteins
Authors: Taylor Thyneice Rochelle , Whalen Margaret M. 
Published: June 2021

Human natural killer cells (NK) are lymphocytes that can recognize and kill virally infected cells, antibody coated cells, and tumor cells without any prior sensitization. Ziram is used as a fungicide in agriculture and as an accelerating agent in the production of latex. Previous studies have shown that ziram inhibits the ability human NK cells to lyse tumor target cells. Mitogen activated proteins kinases (MAPK) are important signaling enzymes in NK cells. These signaling enzymes play a significant role in regulating cytolytic protein expression. Exposure of NK cells to another environmental contaminant, which also blocks NK lytic function, tributyltin (TBT), induced phosphorylation (activation) of MAPK. Thus, disturbances in MAPK activation state could contribute to TBT (and possibly ziram) –induced loss of lytic function. The current study examines whether ziram causes MAPK activation. The MAPKs, p44/42, p38 and JNK were examined. A 10 minute exposure to 10 μM or 5 μM ziram caused a significant increase in phosphorylation of p44/42 (3 fold and 2 fold, respectively). A 10 minute exposure to 10 μM, 5 μM, or 2.5 μM ziram caused a significant increase in phosphorylation of p38 (4 fold, 3 fold, and 2 fold, respectively. These results suggest that MAPK activation may be part of the mechanism by which ziram inhibits NK lytic function, and that MAPK activation may be an effect that is shared by several environmental contaminants that have been shown to decrease NK lytic function. Additionally, NK cell cytolytic protein expression is decreased after various ziram exposure time points.Supported by NIH grant S06 GM008092‐33
Effects of breastfeeding peer counseling for obese women on infant health outcomes
Authors: Chapman Donna J. , Wetzel Katherine , Bermudez‐Millan Angela , Young Sara , Damio Grace , Pérez‐Escamilla Rafael 
Published: June 2021

We evaluated the efficacy of a specialized peer counseling (PC) intervention promoting exclusive breastfeeding (BF) to obese low‐income women. During pregnancy 206 obese women considering BF were randomized to receive a specialized PC intervention (3 prenatal, daily perinatal, 11 postpartum (pp) visits) or standard care. At delivery 154 (76 intervention, 78 control) infants continued to meet inclusion criteria. Demographic, biomedical and infant feeding data were collected at birth, 2 weeks, and monthly through 6 months pp. Medical records were reviewed. Bivariate and logistic regression analyses identified predictors infant health outcomes. Logistic regression analyses adjusted for baseline group differences in age and delivery mode showed control group infants were 3.5 times more likely to be readmitted to the hospital by 3 months of age than those in the intervention group (OR = 3.46, 95% CI 1.01 − 11.89). Main reasons for hospitalization were respiratory infections and fever. These findings may be partly explained by better BF rates in the intervention (vs control) group at 2 weeks (93.1 vs. 83.8% (p=0.08)) and 2 months pp (67.7 vs 54.0% (p=0.11)). These preliminary findings suggest that BF peer counseling reduced the re‐hospitalization rate of infants born to obese, low‐income women.Funded by Donaghue Medical Research Foundation and NIH/NCMHD grant P20MD001765
Peer counselors improve breastfeeding technique among low‐income, obese women
Authors: Morel Katherine , Chapman Donna J , Kyer Nan , Bermudez‐Millan Angela , Young Sara , Perez‐Escamilla Rafael 
Published: June 2021

Data included in these analyses are from a larger randomized controlled trial (RCT) (N=206) evaluating a specialized (SP) peer counseling intervention targeting obese women (3 prenatal, daily hospital and 11 postpartum (pp) visits). The control group received standard (std) care including access to a std peer counselor (PC). These analyses include 45 women from the RCT (Intervention n=22, Control n=23). The objective was to evaluate the impact of a SP breastfeeding (BF) PC on BF technique. Two BF sessions were taped on days 2, 4, and 7 pp. Tapes were edited to remove identifying characteristics and rated independently by 3 Lactation Consultants using the Infant BF Assessment Tool (IBFAT) and Via Christi BF Assessment Tool (VC). T‐tests revealed no significant difference on days 2 or 4 pp. On day 7 pp better BF technique was observed in the intervention group with significantly higher VC scores vs. controls (7.5±1.0 vs. 5.6±3.3, respectively p=.026). IBFAT scores tended to be higher in the intervention vs. controls (11.5±1.2 vs. 9.4±4.3, p=.068, respectively). Maternal report of PC contact during the first week pp was significantly higher in the intervention group vs. controls (143.8±101.6 vs. 39.8±37.1 mins respectively, p=.001). These preliminary findings suggest specialized BF PC provided at a high intensity during the first week pp improved BF technique by day 7 pp.Funded by CDC/ATPR and NIH/NCMHD Grant P20MD001765
Fast‐food consumption among college students and their attitudes toward healthier fast‐food options
Authors: Haines Caitlyn , O'Neil Carol E , Zanovec Michael 
Published: June 2021

Fast‐food meals often provide energy‐dense, nutrient‐poor food; however, attitudes and practices regarding fast‐food consumption among college students is understudied. To determine these, an online survey was developed, piloted tested (n=55), and sent to all students enrolled in the College of Agriculture (n=1,594). A total of 344 students (22% of total; 79% female, 88% white, 68% junior/senior), ages 18–30 y, completed the survey. Eighty‐four percent of students consumed fast‐food with 54% eating it at least once a week. Low cost and good taste were the main reasons students consumed fast‐food, while high cost and preference for other restaurants were main reasons not to consume it. Fast‐food was consumed most often at lunch (46.4%); hamburgers and fried chicken were the top choices; 54.7% of students spent $5–6 per meal. Seventy‐seven percent reported it likely that healthier meals would cost more and of those students, 88% would pay more for healthier meal options; however, few students would opt for choices such as low‐fat milk or salad. Data suggest that college students frequently consumed fast‐food, and would pay more for, but would not select, nutrient‐dense options.Funding: N/A
The Isolation of the Receptor for Advanced Glycation End‐Products from Avian Vasculature
Authors: Cousens Emily N. , Braun Eldon J. 
Published: June 2021

Accumulation of glucose in the plasma results in the formation of Advanced Glycation End Products (AGEs) by a non‐enzymatic reaction with albumin. These products bind to Receptors for AGEs (RAGE) on endothelial cells. This alters the basement membrane structure leading to accumulation of fluid in tissues as seen in Type II Diabetes. Humans normally maintain plasma glucose concentrations of 4.4 to 5.5mM/L whereas birds maintain concentrations of 16.6mM/L or greater. If plasma glucose concentrations in humans exceed 6.6mM/L for 4–6 weeks, symptoms of diabetes will begin to develop. Birds can serve as an animal model for the study of Type II diabetes due to their high plasma glucose levels and that they are insulin insensitive resisting the effects of these levels. In the present study, SDS PAGE and Western Blot analysis were used to isolate RAGE from the vasculature of Mourning Doves. RAGE N‐16 goat polyclonal IgG (Santa Cruz) was used as the primary anti‐body which detects the presence of RAGE in mice, rats, humans and cows increasing the likelihood of detecting RAGE in birds. Vascular tissue isolated from rats was used as a control. We hypothesized that birds lack RAGE as they do not suffer Type II Diabetic pathologies. Our data indicate a band at 55kda suggesting the presence of a RAGE in birds. The density of these receptors in the vasculature is to be determined by immunohistochemistry.E. Cousens was a recipient of an APS UGSRF.