bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationships between changes in iron status and maximal oxygen uptake (VO2 max) after a 5 month iron‐biofortified bean efficacy trial (646.3)
Authors: Luna Sarah , Lung'aho Mercy , Gahutu Jean Bosco , Haas Jere 
Published: June 2021

Objective: To examine the effects of an iron‐biofortified bean intervention on physical performance in Rwandan women assessed by VO2max.Methods: 145 Rwandan women (18‐26 years) were randomized to receive either iron‐biofortified beans or traditional beans twice daily for 5 months. Blood biomarkers and VO2max were measured before and after the feeding period. VO2max was assessed with a mechanically braked cycle ergometer (Monark 874E). Heart rate, VO2, and VCO2 were directly measured with the Cosmed K4B2 system. Non parametric tests and general linear models were used to evaluate the effect of the intervention on blood biomarkers and VO2max.Results: Serum ferritin significantly increased in the iron‐biofortified group (4.0 μg/l increase in median in treatment group, 2.5 μg/l increase in median in control group; p=0.04). VO2max declined in both groups over the course of the intervention with no difference between the high iron and control beans. However, in iron status responders (those with ferritin increase of 15% or more; n=122), women in the treatment group had significantly attenuated decline in VO2max compared with women in the control group (estimate 2.11 ml O2/min/kg, p=0.02).Conclusion: Consumption of iron‐biofortified beans significantly improved iron status in Rwandan women, and improvements in iron status in the iron‐biofortified group attenuated the decline in VO2max.Grant Funding Source: Supported by HarvestPlus
Dietary scopoletin modulates adipose tissue inflammation and lipid accumulation in chronic alcohol‐fed rats (647.12)
Authors: Lee Hae‐in , Sim Mi‐Ok , Ham Ju Ri , Choi Ra Young , Kim Sung Jin , Kim Myung‐Joo , Lee Mi‐Kyung 
Published: June 2021

Chronic alcohol consumption leads to lipolysis and reduction of fatty acid uptake capacity in the adipose tissue, which is associated with dysregulation of lipid metabolism. Therefore, we investigated the dose‐response effects of scopoletin on adipose tissue lipid homeostasis and inflammation in chronic alcohol‐fed rats. Rats were fed a Liber‐Decarli liquid diet contains 5% alcohol with or without three different doses of scopoletin (0.01g, 0.02g, 0.05g/L) for 8 weeks. Normal rats were received isocaloric carbohydrate liquid diet. All doses of scopoletin did not affect the visceral fat mass, but they significantly lowered triglyceride levels compared with the alcohol control group. Scopoletin dose‐independently inhibited lipolysis target gene of adipose tissue, CIDEA, along with lipogenesis genes (PPARγ, SREBP and FASN), while it increased CPT gene level compared with the alcohol control group. Furthermore, all doses of scopoletin significantly down‐regulated mRNA levels of inflammatory markers such as TLR4, NFκB and TNFα as well as plasma TNFα and IL‐6 levels in alcohol‐fed rats. Our findings demonstrated that low‐dose of scopoletin modulated alcohol‐induced dysregulation of lipid metabolism and imflammatory response in the adipose tissue, which was mediated by regulation of TLR4 signaling pathway and lipid metabolism related gene expression.Grant Funding Source: Supported by the National Research Foundation of Korea (No. 2012R1A1A2041931).
Bioactive peptides produced from enhanced common bean cultivars inhibit angiotensin converting enzyme activity (647.14)
Authors: Mojica‐Contreras Luis , de Mejia Elvira 
Published: June 2021

Common bean (Phaseolus vulgaris L.) is a good source of proteins (16‐33%), vitamins, minerals and complex carbohydrates. The objective was to produce, characterize and evaluate the angiotensin converting enzyme (ACE) inhibition and antioxidant capacity (AC) of bioactive peptides from proteins of common bean cultivars from Mexico and Brazil. Bean protein isolates were hydrolyzed by pepsin‐pancreatin and the molecular mass of the produced peptides determined by mass spectrometry. Phaseolin and lectin were the major proteins identified in the studied common beans. Forty seven abundant peptides were identified ranging from 347 to 3067 Da in beans BRS‐Horizonte, BRS‐ Pontal, Perola and Black‐Otomi; the black bean presented the highest amount of identified peptides (689.3, 713.4, 959.6, 981.6 and 1275.7 Da). Common bean Pontal showed the highest AC value (274 mmol ± 0.8 TE/g protein) and BRS‐Horionte the lowest (240 ± 3.8 mmol TE/g protein). ACE inhibition by peptides from Black‐Otomi (YG, RP, GT, GG, DG, NY, CF) was the highest (IC50 = 0.29 ± 0.08 mg /mL) and Pontal the lowest (IC50 = 0.45 ± 0.06 mg/mL), p < 0.05. Mexico and Brazil cultivars showed similar peptide pattern. Peptides from common bean showed high ACE inhibitor activity, high AC, and potential to enhance health and wellness if used as functional ingredients.Grant Funding Source: Supported by CONACYT, Research Council for Science and Technology
Pharmacological blockers of STIM1 inhibit increases in intracellular calcium in horse sweat gland cells (650.2)
Authors: Robertson Jennifer , Bovell Douglas 
Published: June 2021

Calcium is a key second messenger in stimulus‐secretion coupling in human and Equidae sweat gland secretory cells. Upon stimulation, calcium is released from internal stores, facilitating the opening of membrane ion channels and the subsequent formation of secretion in the lumen of the gland. Sustained secretion requires an influx of calcium from the external milieu. This calcium influx is thought to enter the secretory cells via store operated calcium channels. Little is known about store‐operated calcium entry (SOCE) and so we studied its role in horse sweat gland cells from control animals and those that had developed anhidrosis, an inability to produce sweat.We had previously shown the presence of STIM and Orai proteins in cell lines derived from control and anhidrotic animals. The results also indicated a reduction in STIM1 mRNA and protein expression in anhidrotic sweat gland cells. The functionality of the SOCE pathway in both cell lines was investigated in response to agonist stimulation using FURA‐2AM calcium‐imaging techniques. Increases in [Ca2+]i could be abolished to varying degrees in control cells by a variety of known pharmacological blockers of SOCE. Additionally anhidrotic cells showed a significant decrease in [Ca2+]i FURA‐2 ratio in response to agonists when compared to control cells.The results suggest that a reduction of STIM1 expression in the SOCE pathway may play a role in anhidrosis in horses.Grant Funding Source: Supported by Glasgow Caledonian University.
Low‐cost implantable device for electrical stimulation of peripheral nerves in rodents (651.13)
Authors: Dias Daniel , Fazan Rubens , Salgado Helio 
Published: June 2021

The aim of this study was to design and test a low‐cost miniaturized device for acute and chronic electrical stimulation of peripheral nerves. The device consists of a battery‐efficient electronic circuit, equipped with surface mounting devices (SMD), which allows precise adjustment of stimulatory parameters that can be changed with the device implanted in the animal. The frequency of stimulation is monitored by a microcontroller while a miniaturized battery feeds the circuit. The device is embedded in non‐toxic resin and subcutaneously implanted. Male Wistar rats (N=8) were anesthetized with a ketamine/xylazine mixture and implanted with bipolar steel electrodes in the vagus nerve at cervical level. The ECG was recorded during 5 minutes at baseline (Basal heart rate: 290±15 bpm), then the electrodes were connected to the stimulation device and square pulses (20 Hz; 0.1 ms; 3 V) were delivered to the nerve during 1 minute, followed by a recovery period of 5 minutes. It was found that electrical stimulation of the vagus nerve, using the low‐cost device fully designed in our laboratory, induces bradycardic responses (110±24 Δbpm) ceasing after electrical stimulation. This study showed that a low‐cost implantable device was successfully designed and precisely used for peripheral nerve electrical stimulation.Grant Funding Source: Supported by FAPESP, CNPq, CAPES, NIC‐USP
Molecular mechanism of Paclitaxel‐induced degradation of SCG10: a potential neuropathy biomarker (651.14)
Authors: Cintron‐Colon Rigo , Vega Irving 
Published: June 2021

Peripheral neuropathy is a major disorder found in diabetic and chemotherapy‐treated cancer patients; it is commonly due to damage to nerve axons. Paclitaxel is a drug used as chemotherapy agent for the treatment of different types of cancer. The mode of action of Paclitaxel is affecting the microtubules’ dynamic instability required for the proper function of neuronal terminals and cell division. Paclitaxel promotes death of rapid dividing cells (i.e. cancer cells) and induces peripheral neuropathy as a side effect. However, the molecular mechanism that mediates Paclitaxel‐induced neuropathy is still unknown. We showed that the abundance of SCG10 ‐ a microtubule destabilizing protein ‐ decreased in Paclitaxel‐treated neuroblastoma cells. SCG10 protein levels are maintained in PC12 cells, when calpain is inhibited, indicating an involvement in the molecular mechanism activated by Paclitaxel‐treatment. In addition, the inhibition of JNKs after mechanical injured Dorsal Ganglion Root neurons blocks the reduction of SCG10 protein. Thus, JNKs may play an important role in Paclitaxel‐induced calpain‐mediated SCG10 protein degradation. Pharmacological and biochemical approaches were used to test this working hypothesis and identified other proteins associated with Paclitaxel‐induced SCG10 protein degradation. The results will contribute to the understanding of the molecular mechanism associated with the cellular respond to Paclitaxel treatment; information that could be used to prevent peripheral neuropathy as a side effect.Grant Funding Source: BP‐ENDURE NeuroID Program (8R25NS080687).
Tracing neuronal connections through genetic approaches (651.16)
Authors: Corcoran Sarah , Czeisler Catherine , Gygli Patrick , Catacutan Fay , Gokozan Hamza , Linn Sarah , Otero José 
Published: June 2021

Premature babies are at risk for life‐threatening autonomic dysfunction, including abnormal CNS control of breathing. These problems arise in part from immaturity of the autonomic nervous system in premature babies. The transcription factor PHOX2B is a master regulator of autonomic nervous system function as well as the specification of noradrenergic neurons. All autonomic afferent and efferent circuits require normal PHOX2B function, and therefore PHOX2B‐derived neurons must have attained developmental maturity at birth for normal physiological function. Incomplete maturity and/or absence of noradrenergic and serotonergic neuron networks are a proposed mechanism of infant breathing disorders including apnea of prematurity, sudden infant death syndrome, and congenital central hypoventilation syndrome (CCHS). PHOX2B mutations result in the “chemosensation” loss characteristic of CCHS, resulting in poor respiratory drive secondary to hypercarbia (high pCO2). The developmental processes occurring during late embryonic development that permit proper respiration at birth are unknown. So that we may ultimately determine the mechanisms of respiratory neuron maturation in mammals, we validated a transgenic mouse model of neuronal circuitry development. This transgenic mouse reagent (Jackson Labs stock number 010590) shows upon cre‐mediated excision in neurons tdTomato expression in neuronal axons and somata and GFP expression at synapses. Hence, through a genetic approach, we will achieve the capacity to assay neuronal innervation between brainstem nuclei.Grant Funding Source: R21EB017539‐01A1
Prenatal cocaine exposure initiates the release of TIMP‐1 and MMP‐9 in primary neuronal and glial cell cultures (651.21)
Authors: Johnson Marquita , Womble Tracy , Jackson Tanise , Goodman Carl 
Published: June 2021

Drug addiction is a complex phenomenon that is mediated by biochemical events sequential to repeated exposure to a drug. The mechanisms underlying drug addiction include processes similar to those operating in forms of synaptic plasticity. Recently, pro‐addicitve cytokines, tissue inhibitors of matrix metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) have been shown to influence neuronal plasticity consequent to repeated cocaine injections in animal models. The present study was designed to investigate the role of TIMP‐1 and MMP‐9 in the addiction neurobiology of offspring exposed to cocaine during gestation. Time pregnant Sprague‐Dawley rats were treated with 40 mg/kg of cocaine HCl on gestational day (GD) 10‐21. On postnatal day (PND) 2, the brain tissue of the pups was harvested to yield mixed primary neuronal and glial cell cultures. Primary cell cultures were also exposed to a second sub‐lethal dose of cocaine in vitro and their response was measured. An increase in TIMP‐1 and MMP‐9 expression was observed in prenatally exposed primary neuronal and glial cell cultures. Through in vivo and in vitro studies, these findings suggest that exposure to cocaine in utero initiates the release of pro‐addictive cytokines increasing the incidence of addiction in the affected offspring.Grant Funding Source: NIH‐NIMHD G12MD007582
Orpin and its isoform are novel putative calcium binding proteins associated to intestinal and nerve regeneration in the sea cucumber Holothuria glaberrima (651.22)
Authors: Soto‐Acaba Arisnel , Ortiz‐Pineda Pablo , Hernandez‐Pasos Josue , Garcia‐Arraras Jose 
Published: June 2021

Holothuria glaberrima exhibits the capacity to regenerate body parts after injury or loss. This ability is mediated by an initial blastemal formation which requires proliferation and reorganization of precursor cells. Accordingly, various molecules play key roles in different aspects of the regeneration of a body part. The use of microarrays and high‐throughput sequencing lead our laboratory to identify a series of new molecules associated to different processes of regeneration. Such is the case for the protein Orpin.Based on an EST database, we found that Orpin gene is over expressed at early stages of intestinal regeneration. Its expression occurs concomitantly with remodeling of the extracellular matrix. Also, another isoform was identified and both sequences were present in libraries from regenerating nerve and intestinal tissues. The characterization between those sequences indicates that both encode two EF‐hand motifs. Unlike other known calcium binding proteins, they exhibit a signal peptide. The use of Orpin antibodies showed the labeling of the luminal epithelium as well as the radial nerve. Moreover, these antibodies are being used to determine the tissue and temporal specificity of Orpin and its isoform. In order to evaluate the effect of Orpin during regeneration, two His‐tagged fusion proteins are expressed to be injected into regenerating animals. Thus, determining the role of Orpin and its isoform during the regeneration process would help to elucidate the molecular mechanisms involved in different aspects of nerve and intestinal regeneration.Grant Funding Source: NIH (1SC1GM084770)
A2B adenosine receptors promote retention of cardiac stem cells in a myofibroblast‐like state induced by myocardial infarction (652.11)
Authors: Ryzhov Sergey , Sung Bong Hwan , Zhang Qinkun , Weaver Alissa , Gumina Richard , Biaggioni Italo , Feoktistov Igor 
Published: June 2021

Adult cardiac stem cells can contribute to scar formation by acquiring myofibroblast phenotype in response to myocardial injury. Adenosine levels increase in ischemic hearts and modulate cardiac cell functions via binding to adenosine receptors (AR). Here, we tested the hypothesis that A2BAR regulate a reversible transition of cardiac Sca1+CD31‐ mesenchymal stem cells into a myofibroblast‐like state in a mouse model of myocardial infarction (MI). Using flow cytometry, we found that MI resulted in a rapid increase in the numbers of alpha smooth muscle actin (αSMA)‐positive Sca‐1+CD31‐ cells by day 5, followed by gradual decline. Genetic ablation of A2BAR had no effect on accumulation of αSMA‐positive Sca‐1+CD31‐ cells. However, their numbers remained significantly higher in wild‐type (WT) compared with A2BAR knockout (KO) hearts during their deactivation (by 1.2 and 2‐fold on post‐MI days 7 and 14, respectively; p<0.05) indicating that this process is modulated by A2BAR signaling. Furthermore, the numbers of αSMA/collagen I double positive Sca‐1+CD31‐ cells remained higher in WT compared with A2BAR KO hearts by 73%±10% and 54%±6% on post‐MI days 7 and 14, respectively. Our data suggest that A2BAR signaling can play a role in scar evolution by promoting retention of Sca‐1+CD31‐ cells in their myofibroblast‐like state.Grant Funding Source: HL95787‐01A1:04
Biphasic mechanisms of amphetamine action at the dopamine terminal (661.4)
Authors: Siciliano Cody , Calipari Erin , Ferris Mark , Chen Rong , Jones Sara 
Published: June 2021

In light of recent studies suggesting that amphetamine (AMPH) increases spontaneous and electrically evoked dopamine release ([DA]o), we examined discrepancies between these findings and previous literature which has demonstrated marked decreases in [DA]o after AMPH. The current study has refined and expanded the mechanisms of AMPH actions by defining two mechanisms of AMPH effects at high and low doses, one dopamine transporter (DAT)‐independent and one DAT‐dependent, respectively. Using voltammetry in brain slices, we examined the effects of low, moderate, and high concentrations of AMPH across a range of tonic and phasic stimulation parameters (1 pulse; 5 pulse 20 Hz; 24 pulse 60 Hz) in wild‐type (WT) and DAT knockout (KO) mice. We discovered novel, biphasic, concentration‐dependent effects in WT mice, where AMPH increased [DA]o at low concentrations and decreased [DA]o at high concentrations. We then used DAT‐KO animals to examine the mechanisms by which AMPH exerts these effects. In DAT‐KO slices, [DA]o was decreased by all concentrations of AMPH, demonstrating that AMPH‐induced increases in [DA]o are entirely DAT‐dependent, while the decreases at high concentrations are DAT‐independent. We propose that when AMPH concentrations are low, they are insufficient to deplete dopamine vesicles, and therefore AMPH acts solely as a DAT blocker, increasing peak [DA]o. When AMPH concentrations are high, the added mechanism of vesicular depletion leads to reduced [DA]o. The biphasic mechanisms observed here support and extend the established actions of AMPH.Grant Funding Source: Supported by NIH grants DA021325, DA030161, DA006634, DA007246, DA031533, DA031791 and AA007565
Use of geranylgeraniol to rescue osteoblasts and periodontal ligament fibroblasts from zoledronate‐induced apoptosis (663.16)
Authors: Williams Calli , Johnson Brooke , Svrcina Haley , Kawsky Ben , Jones Dan 
Published: June 2021

Bisphosphonate treatments can produce an unwanted side effect of bisphosphonate‐related osteonecrosis of the jaw (BRONJ). One of the most potent bisphosphonates, zolendronate (ZOL), is used to treat postmenopausal osteoporosis, Paget’s disease, and cancer metastasis to bone. Individuals affected with BRONJ are unable to heal from dental procedures, leading to painful oral lesions. The goal of the work presented here was to investigate the ability of GGOH to rescue both murine MC3T3E1 osteoblasts and human periodontal ligament fibroblasts from ZOL‐induced apoptosis. Apoptosis was measured using the APOPercentage® assay. In osteoblasts, 72 hours of 50 micromolar ZOL treatment induced apoptosis by 12.5‐fold but simultaneous exposure to 10 micromolar GGOH decreased apoptosis by 64% (p<0.05). In a separate set of experiments, a booster of GGOH was administered 24 hours after the initiation of treatment, dramatically reducing ZOL‐induced apoptosis by 98% (p<0.0001). In periodontal ligament fibroblasts, ZOL treatment induced apoptosis 10‐fold and GGOH reduced apoptosis by 82% (p<0.05). The booster of GGOH reduced ZOL‐induced apoptosis by 99%. Collectively the data demonstrates the ability of GGOH to potentially rescue both hard and soft tissues of the oral cavity from ZOL‐induced apoptosis with a supplemental dosage of GGOH 24 hours following initiation of treatment essentially eliminating apoptosis.Grant Funding Source: Supported by grants from the Indiana Academy of Science and the Hodson Summer Research Institute
Cardiac hypertrophy leads to coronary microvascular dysfunction and enhanced endothelin‐1/Rho‐kinase signaling in mice with transverse aortic coarctation (676.1)
Authors: Tsai Shu‐Huai , Lu Guangrong , Hein Travis , Kuo Lih 
Published: June 2021

Hypertensive cardiac hypertrophy induced by transverse aortic coarctation (TAC) has been reported to reduce coronary flow reserve in mice, but its impact on oxygen delivery and microvascular function remains unknown. In the present study, we found that induction of TAC in mice for 3‐4 weeks increased heart‐to‐body weight ratio by 55% and decreased cardiac fractional shortening and left coronary arterial blood velocity (LCABV) by 51% and 21%, respectively. The myocardial lactate level was 43% higher in TAC than sham control mice. Isoproterenol (5 µg/g, i.p.) increased heart rate by 20% but the increased LCABV (23%) was observed only in the sham mice. In TAC mice, the superoxide levels in myocardium and coronary arterioles were increased by 1.7‐ and 2.3‐fold, respectively, and the myocardial endothelin‐1 (ET‐1) was increased by 59%. The endothelium‐dependent, nitric oxide (NO)‐mediated vasodilations to acetylcholine and adenosine, but not endothelium‐independent vasodilations to NO donor sodium nitroprusside, were impaired in TAC mice. The Rho kinase (ROCK)‐dependent vasoconstriction to ET‐1 was enhanced and the expressions of ROCK‐1 and ‐2 were increased in coronary arterioles of TAC mice. We conclude that myocardial pressure overload leads to cardiac deficiency, coronary microvascular dysfunction and ischemia possibly due to oxidative stress, elevated ET‐1/ROCK signaling and compromised NO function.Grant Funding Source: Supported by Kruse Endowed Research Fund from Baylor Scott & White Healthcare
Protein kinase C alpha is a target for the meprin B metalloproteinase (690.14)
Authors: Boyd Sada , Newman Robert , Ongeri Elimelda 
Published: June 2021

Meprin metalloproteinases have been shown to play a role in the progression of diabetic nephropathy (DN) in both mice and humans. However, the mechanisms involved are not fully understood. The objective of this study was to determine whether PKC, a serine/threonine kinase known to play a role in DN, is a meprin substrate. Activated forms of purified recombinant meprin A and B were incubated for 0‐4 h with cytosolic‐enriched proteins from meprin αβ double knockout mouse kidneys (which lack endogenous meprins) and protein lysates extracted from Mardin‐Darby canine kidney (MDCK) cells (which do not express meprins). The levels of PKCα were determined by Western blot analysis using anti‐PKCα specific antibodies coupled with optic densitometry. Incubation with meprin B significantly reduced the levels of PKCα present in the kidney proteins and MDCK lysates. This decrease was not observed in proteins incubated with meprin A or control reactions without meprins, suggesting isoform‐specific degradation of PKCα. To confirm the degradation, human PKCα proteins were expressed in yeast, purified by GST‐affinity chromatography, and incubated with the activated meprins. These data suggest that meprin B may impact kidney function via proteolysis of PKCα. Consistently, PKC isoforms are upregulated in DN and PKCα has been shown to play a role in the development of albuminuria in mice with streptozotocin‐induced type 1 diabetes.Grant Funding Source: Supported by NIGMS (SC3GM102049)