bluuebunny/crossref_metadata_2025_split huggingface dataset:
PDE4B2 is Strongly Expressed in Blood Vessels and is Inhibited by Rolipram, Ameliorating Hepatic Ischemia Reperfusion Injury in a Rat Model
Authors: Frimodig Jane , Matheson Paul , Matheson Amy , McClain Craig 
Published: April 2020

BACKGROUNDIschemia reperfusion (IR) injury is caused by the loss and subsequent return of blood flow. It is a limiting factor in the success of liver transplantation. Reperfusion initiates inflammation and recruitment of neutrophils, which are main effectors of liver damage in IR. The Phosphodiesterase‐4 (PDE4) inhibitor rolipram is anti‐inflammatory, since PDEs degrade cAMP, and higher cAMP levels are known to dampen inflammatory signaling. Isoform PDE4B2 is strongly expressed in the brain, in neutrophils and activated monocytes, and in Kupffer cells in the liver. Here we show for the first time that PDE4B2 antibody also stains blood vessel cells in the liver.HYPOTHESISRolipram is able to protect the liver during IR injury.METHODSMale Sprague‐Daley rats were randomized to six groups (n=6–8 per group): 1) sham, 2) sham + rolipram, 3) 40% IR, 4) 40% IR + rolipram, 5) 70% IR, and 6) 70% IR + rolipram. Two levels of severity were attained by clamping either 40% (left lobe) or 70% (left and median lobes) of the rat liver. 1 hour of occlusion was followed by 3 hours of reperfusion. I.V. rolipram (3 mg/kg) was given at the end of the ischemic period. After sacrifice, blood chemistry, histology, and RT PCR were performed. ANOVA was followed by Tukey’s or Bonferroni’s tests. P values < 0.05 were significant. Frozen immunofluorescent histology revealed colocalization of PDE4B2 (short isoform) with CD31, a marker for blood vessels.RESULTSBoth 40% and 70% IR elevated serum ALT, an indicator of liver damage. Rolipram lowered ALT levels in 40% IR. Histology showed necrosis and increased neutrophil infiltration, which improved with rolipram, in both 40% and 70% IR. Expression of PDE4B2 was elevated in 70% IR, and lowered by rolipram. Correlation analysis revealed that PDE4B2 mRNA increased with increasing ALT, necrosis, and neutrophil count. Both neutrophils and injury markers correlated most strongly with expression of the transcription factors (TFs) activating transcription factor‐3 (ATF3) and interferon regulatory factor‐1 (IRF1). These two genes also correlated positively with PDE4B2 expression. PDE4B2 antibody strongly stained some endothelial and perivascular cells of the liver, indicating that these cells may be playing some kind of role in the protection of rolipram in IR.CONCLUSIONThese data suggest that inhibition of PDE4 reduces IR injury by decreasing neutrophil recruitment, and that IR injury increases with TFs IRF1 and ATF3. Further experiments are needed to determine conclusive effects of this change in TF expression. Histology showed strong staining of PDE4B2 in blood vessels. Mechanisms of PDE4B2 inhibition protection of the liver in blood vessels cells, however, remain to be elucidated. Ultimately, liver injury was decreased by rolipram; therefore, phosphodiesterase‐4 inhibition is a potential therapy for IR injury.Support or Funding InformationNIH
NMR and Mass Spectroscopy Based Comparison of Blood Metabolites from Dantrolene and SR59230A Treated Arctic Ground Squirrels
Authors: Macander Sophia , Johannsen Michelle , Hunstiger Moriah , Murphy Carl , Thao Shelly , Oliver S. Ryan 
Published: April 2020

Arctic ground squirrels (AGS) hibernate during winter, undergoing cycles of torpor, where body temperatures plummet as low as −3°C followed by rapid rewarming to 37°C during interbout arousals (IBA). While IBAs only occur in certain species that experience torpor, they offer a unique model into which one can observe the specific mechanisms responsible for thermogenesis. Rapid rewarming at IBA onset increases AGS body temperature above 15°C through the activation of brown adipose tissue (BAT). Above 15°C, shivering thermogenesis is able to contribute to warming back up to original body temperature. However, the relative contributions of these two thermogenic processes during IBA is not well understood. AGS were treated across periods of coupled torpor cycles, whereby during the second cycle AGS were treated with either carrier (control) or a selected inhibitor. BAT inhibition using SR59230A, a β3‐adrenergic receptor inhibitor, would be expected to strain the rapid heat production. Shivering thermogenesis utilizes calcium cycling and the Ryanodine receptor in skeletal muscles; the use of dantrolene reduces the thermogenic mechanism needed to reach 37°, effectively inhibiting the Ryanodine receptor in muscle. Relative concentrations of blood plasma metabolites were quantified using nuclear magnetic resonance (NMR) to compare whole and polar extracted plasma. The NMR method was compared against full metabolomic analysis performed using liquid chromatography tandem mass spectroscopy (LC MS‐MS). NMR analysis resulted in higher peak resolution quality and increased metabolite identification in polar and lipid extraction samples compared to whole samples, whereas LC MS‐MS provided a greater abundance of metabolites. Overall, total metabolites were significantly reduced during hibernation. Dantrolene treated AGS had alterations in metabolites indicative of increased energy demand. Furthermore, SR treatment resulted in profiles describing decreased beta‐oxidation and generally lower total metabolites compared to Dantrolene. These trends indicate that changes in calcium cycling and BAT stimulation during hibernation can have profound effects on the animals ability to efficiently balance energy usage.Support or Funding InformationResearch reported in this publication was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103395. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the NIH. BLaST is supported by the NIH with the linked awards; TL4GM118992, RL5GM118990, UL1GM118991.
Cardiovascular Responses to Soft Drink Consumption during Mechano‐ and Metaboreceptor Stimulation
Authors: Ji Wenjie , Reed Emma L. , Kueck Paul J. , Bloomfield Adam C. , Zazulak Hannah E. , Chapman Christopher L. , Schlader Zachary J. , Johnson Blair D. 
Published: April 2020

IntroductionAcute consumption of a high‐fructose, caffeinated soft drink exacerbates the increase in blood pressure during exercise in the heat. The mechanoreflex and metaboreflex are important contributors to the blood pressure response during exercise. However, the effects of acute soft drink consumption on the mechanoreflex and metaboreflex, independent of heat stress, are currently unknown.ObjectiveWe tested the hypothesis that consumption of a high‐fructose, caffeinated soft drink would exacerbate cardiovascular responses to static handgrip (HG) exercise and post exercise muscle ischemia (PEMI) compared to water consumption.MethodsEight healthy adults (Age: 26±7 years, 3 females) consumed 500 mL of water (H2O) or soda (Soda, Mountain Dew®) in a randomized, double‐blind study design in a moderate thermal environment (24±1%, 21.7±6% relative humidity). After consuming the assigned beverage, subjects lied on their left side quietly for 20 min and then completed a 10 min baseline (BL) followed by 2 min of static HG at 30% of maximal voluntary contraction followed by 2 min of PEMI. Heart rate (HR, ECG) and mean arterial blood pressure (MAP, finger photoplethysmography) were recorded continuously. Stroke volume (SV) was estimated using Modelflow. Cardiac output (Q) was calculated as HR×SV. Total peripheral resistance (TPR) was calculated as MAP/Q. Data were analyzed as a change from baseline (Δ) to the last 30 s of HG and the last 30 s of PEMI. Data are reported as Δmean±SD.ResultsAt BL, there were no differences between Soda and H2O for HR (Soda: 67±9; H2O: 64±8 bpm, P=0.27), MAP (Soda: 79±10; H2O: 83±6 mmHg, P=0.16), or SV (Soda: 101±22; H2O: 95±11 mL, P=0.32). Q was higher with Soda (6.5±1.5 L/min) vs. H2O (5.9±0.8 L/min, P=0.04) and TPR was lower with Soda (12.3±2.5 mmHg/L/min) vs. H2O (14.6±2.1 mmHg/L/min; P=0.02) at BL. During HG, ΔHR (Soda: 15±12; H2O: 13±13bpm, P=0.57), ΔMAP (Soda: 12±13; H2O: 17±7mmHg, P=0.10), ΔSV (Soda: −4±13; H2O: −2±8 mL, P=0.71), ΔQ (Soda: 1.0±1.4; H2O: 1.1±0.9 L/min, P=0.93), and ΔTPR (Soda: −0.1±2.8; H2O: 0.5±2.0 mmHg/L/min, P=0.38) did not differ between drinks. Additionally, there were no differences between drinks during PEMI for ΔHR (Soda: 1±8; H2O: 2±9 bpm, P=0.67), ΔMAP (Soda: 12±13; H2O: 16±11 mmHg, P=0.22), ΔSV (Soda: −1±17; H2O: 4±8 mL, P=0.34), ΔQ (Soda: 0.0±1.1; H2O: 0.4±0.7 L/min, P=0.16), and ΔTPR (Soda: 1.6±2.4; H2O: 1.6±2.9 mmHg/L/min, P=0.98).ConclusionThese preliminary data indicate that acute consumption of a high‐fructose, caffeinated soft drink does not exacerbate cardiovascular responses to mechanoreflex and metaboreflex stimulation in moderate thermal conditions. Further investigation is warranted to determine if the mechanoreflex and/or the metaboreflex are altered following acute consumption of a high‐fructose, caffeinated soft drink during heat stress.
Sex Differences in Fetal Programming of Blood Pressure and Kidney Gene Expression of Intrauterine Growth Restricted Mouse Model
Authors: Yokota Rodrigo , Maeda Kenji J. , Garrett Michael R. , Intapad Suttira 
Published: April 2020

The fetal environment is critical in determining future cardiovascular‐renal function in adulthood. Intrauterine growth restriction (IUGR) results in an unfavorable intrauterine milieu, and can lead to hypertension, renal, and cardiovascular disease of the offspring later in life. However, the underlying mechanisms linking IUGR to cardiovascular and renal afflictions remain unclear. IUGR offspring exhibit impaired kidney development. Furthermore, IUGR reprograms kidney function, resulting in an increase in blood pressure (BP) and susceptibility to kidney injury in the adult. While some renal factors have been postulated, others remain to be elucidated. Here, we have utilized a relevant preclinical mouse model of IUGR induced by reduced uterine perfusion pressure (RUP) to explore the effect of IUGR on renal gene expression patterns as well as sex differences. Pregnant C57bl/6J mice underwent sham or reduced uterine perfusion (RUP) at day 13 of gestation with delivery at full term. IUGR offspring (from RUP dam) had a lower birth weight than control (p<0.05). At 24 weeks of age, control and IUGR mice were subjected to BP measurement. Kidney tissues from control and IUGR mice were isolated and mRNA from these tissues was subjected to microarray analysis to determine differential gene expression. We found that male IUGR offspring had a significantly higher BP compared to male controls (p<0.05). No significant differences in BP were found between female IUGR and female controls, suggesting that sex differences in IUGR programs increased BP in mice. Microarray analysis, at a statistical cutoff of p < 0.05, demonstrates clear sex differences between IUGR and control mice. Of the total number of genetic elements (n = 39,724), 8,356 were significantly different due to IUGR alone, with the majority of these differences occurring in the males (8,319). Network analysis indicated a strong effect on several pathways such as protein processing in the endoplasmic reticulum, oxidative phosphorylation, and mTOR signaling pathways in male IUGR compared to male controls. Interestingly, two pathways (PPAR signaling and AMPK signaling) were significantly altered by IUGR in the female group. In conclusion, there is a clear sex difference in the effect of IUGR on BP and kidney gene expression. The functional implications of these novel factors need to be further investigated.Support or Funding InformationDr. Intapad was supported by funding from the AHA 16SDG27770041, ASN Kidney Research Career Development grant, and grant P20GM109036 K. J. Maeda was supported by National Institutes of Health Grants T32HL‐105324 and 20PRE352000021. Dr. Garrett was supported by P20GM‐103476, P20GM‐104357 and P20GM‐121334
Microtubule Arrangement and FKBP51 Localization is Altered in BMPR2‐Deficient Pulmonary Artery Endothelial Cells Isolated from a Rat Model of PAH
Authors: Hamilton Caleb L. , Snyder Emily A. , West Brittanee A. , Vasauskas Audrey A. 
Published: April 2020

Pulmonary arterial hypertension (PAH) is an incurable vasoconstrictive pathology of which there are limited palliative treatments. The hallmarks of PAH include vascular smooth muscle cell proliferation and endothelial dysfunction in the small pulmonary arteries. Endothelial cytoskeletal defects have been implicated in BMPR2‐associated PAH, and BMPR2‐silencing alters cytoskeletal arrangement in pulmonary artery endothelial cells (PAECs). Indeed, targeting cytoskeletal proteins, particularly microtubules, may be a novel approach to PAH treatment as microtubule disruption has been efficacious in the treatment of other inflammatory and proliferative diseases. FK506‐binding protein 51 (FKBP51), a peptidyl‐prolyl isomerase member of the immunophilin family, is a known regulator of the glucocorticoid receptor and its expression is upregulated upon glucocorticoid receptor activation. Furthermore, FKBP51 is a binding partner to Hsp90 and stabilizes microtubules in PAECs. Here, we show microtubule disruption and altered FKBP51 distribution in PAECs from a rat model of PAH. PAECs isolated from the Sugen/hypoxia rat model of PAH (PAH PAECs) or normoxic control cells were gifted from the University of South Alabama. The PAH PAECs have lower BMPR2 gene expression than normoxic controls, as shown by real‐time PCR. These cells also demonstrate decreased BMPR2 signaling compared to normoxic control PAECs, as demonstrated by lower ID‐1 expression levels upon BMP4 or BMP6 stimulation. Immunocytochemistry studies of α‐tubulin indicate microtubule disorganization in PAH PAECs, as compared to the normoxic control PAECs, which demonstrate normal perinuclear distribution of interphase microtubules. Immunocytochemical staining of FKBP51, using a novel antibody developed by our laboratory, reveals a microtubule‐like distribution of FKBP51 in normoxic control PAECs. Upon treatment with the synthetic glucocorticoid dexamethasone (DEX), FKBP51 is predominantly observed in the nucleus of normoxic control PAECs, with reduced cytosolic organization and distribution. PAH PAECs, however, showed diffuse cytoplasmic staining of FKBP51, with no change in distribution upon DEX treatment. Western blot analysis of PAEC nuclear fractions also demonstrated greater protein levels of FKBP51 upon DEX treatment, compared to DEX‐treated PAH PAECs. Taken together, these data indicate that microtubule rearrangement is evident in BMPR2‐deficient PAH PAECs, and FKBP51 dysregulation may play a role in cytoskeletal abnormalities as well as the disruption of metabolic homeostasis in these cells.Support or Funding InformationSupported by NIH1R15HL137135‐01A1
Characterization of a putative antibiotic producing microbe from the plastics‐here
Authors: Pinkowski Dakota , Louks John , Simmons Rachel Elizabeth 
Published: April 2020

In this study we are identifying an unknown, putative antibiotic producing bacterium found on a piece of submerged coastal plastic. We isolated genomic DNA, amplified hypervariable regions of 16S rRNA and used Oxford Nanopore sequencing to characterize this species. Through this process we have identified this bacterium as Phaeobacter inhibens. Further characterization of this sample based on a partially complete genome will be discussed as well as potential antibacterial properties that could prove useful for future research and medicinal purposes.Support or Funding InformationThis project is supported by the NSF‐HSI grant #1832545, and from NU internal grants. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.
Bio‐lethal effect of BAPCs‐dsRNA formulations for genetics‐based pest management
Authors: de Melo Barros Sheila , Van Ekert Evelien , Whitaker Susan K. , Avila L. Adriana , Stewart William , Gillian Jason , Aulisa Lorenzo , Tomich John M. 
Published: April 2020

The use of RNA interference (RNAi) or double‐stranded RNA (dsRNA)‐mediated gene silencing has become one of the most promising tools on the field of pest management. One of the barriers for RNAi efficiency, however, has being the fact that it needs to be rapidly taken up by cells before being degraded by nucleases. In this context, the nanoscale delivery system formed by Branched Amphiphilic Peptides Capsules (BAPCs™) are proposed as a solution for a safer and more efficient cellular uptake of lethal dsRNA constructs. BAPCs can be synthesized in a varied diameters ranging from 10 to 500 nm. BAPCs act as cationic nucleation centers for nucleic acids, generating peptide‐DNA or dsRNA complexes that are readily taken up by eukaryotic cells, escape late endosomes, and lead to the release of the surface‐bound nucleic acids that alter protein expression. Recently, we described the use of BAPCs for suppressing the translation of genes transcripts related to the unfolded protein response (UPR) in Tribolium castaneum and Acyrthosiphon pisum, which led to a premature death with a 50% increase in lethality when compared to dsRNA alone. For this study, BAPCs were combined with 3 different concentrations of a dsRNA supplied by GreenLight Biosciences™. The test sequence contained ~600 bp. Its lethal bio‐efficacy was compared to the dsRNA by itself on Colorado potato beetle. The tests using unformulated dsRNA at 0.00005, 0.0001 and 0.001, mg/mL exhibited a lethal effect of 10%, 30% and 50% lethality after 8 days by contrast of 30%, 60% and 90% of BAPCs‐dsRNA formulations, followed by approximately 40% reduction on leaf consumption in comparison to the unformulated material. The present results have shown that BAPCs‐dsRNA formulations offer a considerable increase in lethality bio‐efficacy over unformulated dsRNA indicating an additive effect in dsRNA delivery over using dsRNA by itself.Support or Funding InformationThis project is a result of a collaboration between GreenLight Biosciences&[trade], Inc. and Phoreus Biotechnology, Inc.
Comparison of Autoregulation Index during Sit‐To‐Stand in Young Healthy Individuals across Races
Authors: Liu Jie , Favre Michelle , Iring Stephanie , Le Cao Thuy Tien , Serrador Jorge 
Published: April 2020

Cerebral autoregulation is an important mechanism to protect the brain by maintaining the brain perfusion over varying blood pressures. The cerebral blood flow velocity response to Sit‐To‐ Stand maneuver has been widely used to assess dynamic cerebral autoregulation. Previous work has demonstrated sex differences in autoregulation; however, little is known about the impact of race. Potential racial differences in cerebral autoregulation may contribute to different incidences of cerebrovascular events between different races. Therefore, the purpose of this study was to compare the Autoregulatory index between four different racial groups. We enrolled 55 young healthy subjects (aged 18~35 years) with four racial groups, i.e. White/Caucasian (Age 27±5; n=11; 5 Males), Black/African American (Age 28±6; n=8; 4 Males), Latino (Age 28±6; n=6; 2 Males), and Asian (Age 27±3; n=30; 15 Males). The transcranial Doppler was used to continuously record the cerebral blood flow velocity at middle cerebral artery during 3 repeated sit‐to‐stand maneuvers, with simultaneous measurements of blood pressure, heart rate, and end‐tidal CO2 (ETCO2). There was no difference in demographic variables across groups except for BMI (24±4, 26±4, 27±5, and 23±3; kg/m2, P=0.043). Similarly, there were no differences in baseline cerebral blood flow velocity, blood pressure or heart rate with the exception of ETCO2 (35±3, 40±4, 35±3, and 38±3 mmHg, P=0.003). We found no differences between groups in the physiological response during sit‐to‐stand. Similarly, autoregulatory index was similar across all racial groups (3.6±2.4, 3.9±1.2, 3.3±2.6, and 3.6±1.5, P=0.948). These data suggest that cerebral autoregulation is similar in young healthy individuals across different races. However, these findings must be interpreted with caution due to the small number of participants in the various racial groups. Future studies are warranted to include larger sample size, older subjects and also to consider sex differences within each race.Support or Funding InformationSupported by the Funding from Rutgers University and U.S. Department of Defense.
Calf Circumference Is Associated with Malnutrition in Elderly Patients on Hemodialysis
Authors: Rodrigues Renata Gomes , Dalboni Maria Aparecida , Moyses Rosa Maria Affonso , Elias Rosilene Motta 
Published: April 2020

Background and objectivesChronic kidney disease (CKD) is considered a world health problem and is associated with a high mortality rate, particularly among elderly patients. With the aging population, there has been an increase in elderly patients starting hemodialysis. Elderly patients are subject to a high burden of comorbidities and the risk of falls and fractures is a concern since it can lead to hospitalization and death. Falls occur as a consequence of clinical pathologies and are aggravated by hemodialysis‐associated hypotension. Sarcopenia, defined as the loss of muscle mass and strength that occurs with aging is commonly seen in these patients. Measurement of calf circumference (CC) is an easy and not expensive tool to assess muscle mass. The objective of this study was to test the association between CC, a marker of sarcopenia, and the risk of falls and fractures in elderly patients on hemodialysis.MethodsThis is a cross‐sectional study that included clinically stable patients ≥ 65 years, on maintenance hemodialysis. The same observer measured the calf circumference in the non‐dominant leg. Clinical and biochemical data were collected from the charts.ResultsPreliminary results of 96 patients (age 73 ± 6 years, % mean) showed a CC of 32.7 ±3.5 and 31.5 ± 4.6 cm in men and women, respectively, p=0,143). History of falls was found in 20 patients (40.6% with low CC vs. 36.8% with normal CC, p=0.789). Patients with low CC according to gender presented lower body mass index (p=0.0001) and had lower weight gain between dialysis sessions (p=0.008). They did not differ from patients with normal CC according to age, gender, race, blood pressure, serum albumin, and presence of comorbidities such as hypertension, diabetes, and congestive heart failure.ConclusionsAlthough the measurement of CC did not predict falls in elderly patients on hemodialysis, it did identify patients with low body mass index, which is probably related to sarcopenia. Further studies are necessary to definitely conclude the lack of association between CC and falls.