bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating EAAT3 trafficking through the secretory pathway
Authors: Saha Kusumika , Steinkellner Thomas , Hofmaier Tina , Kudlacek Oliver , Sucic Sonja , Freissmuth Michael , Sitte Harald 
Published: June 2021

The eukaryotic secretory pathway allows synthesized proteins to leave the endoplasmic reticulum and makes its way to the cell surface where it carries out its individual functions. The intracellular pathway through the various cellular compartments comprises different coat protein complexes, namely coat protein complex II (COPII) and coat protein complex I (COPI).The excitatory amino acid transporter 3 (EAAT3) mediates the regulation of the synaptic transmission at the glutamatergic synapse by transporting the neurotransmitter glutamate. Our goal is to understand the key mediators of the secretory pathway who play a pivotal role in transporting the EAAT3 to the surface. The work focuses on looking at the EAAT3 as a cargo within the cells and following it through the anterograde pathway mediated by COPII. The knowledge gained from this work will be able to shed some light in the pathway of EAAT3 through the cell and can be further extrapolated to the other glutamate transporter family members. Furthermore, the aim of the presented work is to understand key factors that regulate the surface expression of EAAT3 and the role they may play in health and disease.
Bile Acids and Bile Salts of the Arabian Gulf Catfish Arius Bilineatus, Val
Authors: Al‐Hassan Jassim , Oommen Sosamma , Paul Bincy , Afzal Mohammad 
Published: June 2021

Catfish gall bladders were collected from freshly caught catfish. Bile solution was collected by rupturing the gall bladder. The bile solution was freeze dried and extracted with chloroform:methanol (1:2). The solvent mixture was evaporated and the residue was extracted with methanol. The extracted material was subjected to hydrolysis to remove the conjugated parts from the bile acids and together with standards were methylated. MS analysis was performed on the methylated products. The following bile acids were obtained: Cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid. Trimethylsilyl (TMS) derivatization was done on the extracted material and analyzed by GCMS to give allocholic acid. The extracted bile salts and bile acids were also separated in LC/MS QTOF using acetonitrile: water as solvent. The following conjugated bile acids were obtained: Taurochenodeoxycholic acid, glycolithocholic acid, glycodeoxycholic acid, glycocholic acid, and cholic acid conjugated with Cysteinolic acid.(This project was funded by The Research Sector of Kuwait University Grant # SL04/09. Spectroscopic analysis was performed by Science analytical Facilities, KU<a name=“_GoBack”></a>).
Obesity Significantly Intensifies the Depressive Symptom among Adults with Neck or Back Pain
Authors: Lawrence Wayne , Badana Adrian , Barnett Gloria , Sexton Jessica , Oliver Kirsten , Hogges Jamesa , Zhang Jian 
Published: June 2021

ObjectiveObesity and back or neck pain are the leading chronic conditions among adults in the United States, yet the interaction between these two conditions and the role in the development of depressive symptom have not yet been investigated.Methods: National Health and Nutrition Examination Survey data from 2009‐2010 of 1,952 men and 1,971 women aged 20 years or older was used to calculate odds ratios (OR) of depression among normal, overweight, and obese men and women that reported a presence or absence of neck or back pain.Results: The prevalence of moderate/severe depression were 1.9 (SE: 0.18) and 3.46 (SE: 0.27) percent among men and women, respectively. Using neck or back pain‐free adults with similar body mass index (BMI) level as the reference, the odds ratios (OR) of depression were 2.60 (1.04‐6.51), 3.03 (1.10‐8.37), and 11.6 (6.01‐22.5) among normal, overweight, and obese men that reported neck or back pain. The ORs of depression were 2.28 (1.08‐4.81), 2.97 (1.14‐7.80), and 3.05 (2.03‐4.58) among normal, overweight, and obese women that reported neck or back pain. These estimates were obtained after adjustments for relevant health history and socioeconomic factors.ConclusionsExcess body weight significantly intensifies the depressive symptoms and increases the prevalence of depression among adults diagnosed with neck or back pain. Obesity prevention may improve the both mental and physical well‐being among adults.
in vivo Tracking and Effects of SPIO‐labeled Mesenchymal Stem Cells in a Porcine Model of Abdominal Aortic Aneurysm
Authors: Li Jennifer , Lee Dong , Han Daniel , Rawal Bhakti , Briley‐Saeboe Karen , Mani Venkatesh , Gillespie Virginia , Hajjar Roger , Fayad Zahi , Tadros Rami , Faries Peter 
Published: June 2021

Abdominal aortic aneurysm (AAA) pathogenesis involves extracellular matrix remodeling, degeneration, and inflammation, making it a promising target for cell‐based therapy. This study demonstrates, in a large animal model, the feasibility of tracking implanted mesenchymal stem cells (MSC) on in vivo MRI with Superparamagnetic Iron Oxide (SPIO) labeling and then characterizing potential reparative effects.Dosimetry and cell viability experiments with SPIO were performed on porcine BM‐MSCs. Tracking of SPIO‐labeled MSCs was performed with 3T MRI. Histological changes in iron, elastin, collagen, and smooth muscle actin were assessed, and levels of inflammatory markers were quantified using RT‐PCR.Optimal imaging and cell viability were achieved with SPIO conc of 500ug/mL. SPIO‐labeled MSCs demonstrated positive CD90 and negative CD45 markers, consistent with the MSC phenotype. MRI tracking demonstrated circumferential migration of the implanted MSCs. Histological analysis demonstrated an increase in collagen, elastin, and smooth muscle cell synthesis in treatment groups compared to controls, as well as mild decrease in inflammatory markers such as MMPs ‐2, ‐3, ‐9, IL‐1B, and TNF‐alpha.MSCs can be successfully labeled, implanted, and tracked by in vivo MRI in a large animal model of AAA. The MSCs may stabilize AAA degeneration through the production of new collagen, elastin, and smooth muscle cells, as well as decreasing inflammation.
Evolution of Transcriptional Regulation of Duplicated Fatty Acid‐Binding Protein Genes by PPARs in Zebrafish: a Pharmacological Approach
Authors: Laprairie Robert , Denovan‐Wright Eileen , Wright Jonathan 
Published: June 2021

Duplication of genes is thought to facilitate increasing organismal complexity. Duplicated genes may be retained in the genome if one of the duplicates acquires a novel function, or the functions of the ancestral gene are subdivided between the duplicates. A likely process for the retention of duplicates is the loss or gain of regulatory elements in the promoters of duplicated genes.The objective of this study was to explore the evolution of gene promoters using the multigene family of fatty acid‐binding proteins (fabp) in zebrafish. Previous studies had implicated the peroxisome proliferator‐activated receptors (PPARs) in the regulation of some fabp genes. The promoters of the zebrafish fabp1a, fabp1b.1 and fabp1b.2 genes, duplicated by a whole genome duplication (fabp1a and ancestral fabp1b) followed by a tandem gene duplication (fabp1b.1 and fabp1b.2), were cloned into firefly luciferase reporter plasmids, transfected into HEK cells, and tested in the presence of PPARα‐ and PPARγ‐selective agonists. Expression of these genes was further analyzed by qRT‐PCR in explant cultures of zebrafish liver and intestine treated with PPAR agonists.fabp1a expression was selectively increased by PPARα‐agonism in HEK cells and intestine. fabp1b.1 expression was selectively increased by PPARγ‐agonism in HEK cells and liver. fabp1b.2 promoter activity was not induced by PPAR modulation. The differential PPAR regulation of the duplicated fabp1 genes provide evidence of divergence of regulatory elements in these gene promoters, which may account for the retention of the duplicated fabp1 genes in the zebrafish genome.Funding from NSERC, CIHR, and Dalhousie University.
In Vivo Evaluation of Two 5‐Aminosalicylic Acid Derivatives Considered as Potential Therapeutic Agents
Authors: Gutierrez Sanchez M , Rosales Hernandez M , Padilla Martinez I , Correa Basurto J , Mendieta Wejebe J 
Published: June 2021

Several studies have shown that myeloperoxidase (MPO) is intimately involved in the initiation and progression of many inflammatory diseases [Lee et al., 2013].Based on the foregoing, our research group has shown recently that two new derivatives of the 5‐aminosalicylic acid (5‐ASA), the 5‐{[(2E)‐3‐bromo‐3‐carboxyprop‐2‐enoyl]amino}‐2‐hydroxybenzoic acid (1) and 5‐[(4‐carboxybutanoyl)amino]‐2‐hydroxybenzoic acid (2), inhibit the catalytic activity of MPO and have antioxidant capacity in vitro. Therefore, this study aimed to evaluate the inhibitory effect of these compounds on catalytic activity of MPO in vivo.Compounds 1 and 2 were synthesized and characterized chemically. The acute toxicity was determined in two rodent species [Guía 425, OECD, 2008]. The edema induction model was performed in the mouse ear by using 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) [Salazar et al., 2011]. The MPO activity was determined using the oxidation method of O‐dianisidine in presence of hydrogen peroxide [Quaiyoom et al., 2012].Both compounds were obtained with acceptable yields (70%). These showed be safe for their use in rat and mouse (DL50˃1098 mg/kg). Furthermore their administration in ears of TPA‐treated mice, led to a significant decrease of catalytic activity of MPO in comparison with the positive control (indomethacin).Therefore, these results suggest continue with the preclinical study of both compounds, since these could be used in future as potential therapeutic agents for the treatment of inflammatory diseases.
Global Intracoronary Allogeneic Cardiosphere‐Derived Cells Promote Functional Repair Without Affecting Myocardial Perfusion in a Porcine Model of Acute Myocardial Infarction
Authors: Weil Brian , Goelz Andrew , Suzuki Gen , Palka Beth , Canty John 
Published: June 2021

ObjectiveIntracoronary cardiosphere‐derived cells (icCDCs) exert beneficial effects on left ventricular (LV) function in experimental models of myocardial infarction (MI), but the role of microvascular remodeling and improvements in myocardial perfusion are unclear. We determined whether global icCDCs administered after reperfusion promote functional repair by improving myocardial blood flow in a swine model of acute MI.MethodsImmunosuppressed swine (cyclosporine 100 mg/day, n=15) underwent a 60‐minute LAD occlusion. After 30 minutes of reperfusion, animals were randomized to receive vehicle or 20 x 106 allogeneic CDCs infused into the 3 major coronary arteries at 106 cells/min under continuous flow. LV function (CT) and myocardial perfusion (microspheres) were assessed at baseline and 1‐month after MI, at which point the heart was excised for histological assessment of microvascular density.ResultsSegmental wall thickening in the infarct, border, and remote myocardium was higher in icCDC‐ vs. vehicle‐treated animals (Table). As a result, there was a significant improvement in LV ejection fraction (57.7 ± 2.7 vs. 50.7 ± 4.1%, p<0.05). However, resting and adenosine‐dilated blood flow remained similar between groups, with a comparable density of arterioles and capillaries throughout the LV in each group.
imageConclusionThe functional improvement afforded by allogeneic icCDCs administered immediately after acute MI is independent of angiogenesis with no changes in microvascular density or myocardial perfusion.SupportNational Heart Lung and Blood Institute (HL‐055324, 1F32HL‐114335)
Least Significant Change of Body Composition and Bone Mineral Density Measured by Dual energy X‐Ray Absorptiometry
Authors: Najm Nadia , Popp Collin , Traylor Daniel , Jesch Elliot 
Published: June 2021

IntroductionThis study is designed to determine the least significant (LSC), or the least amount of change that can be considered significant when measuring body composition with Dual Energy X‐ray Absorptiometry (DXA). In the past five years, researchers have focused on measuring the LSC of bone mineral DXA scans or body composition DXA scans in athletic populations. However, none have measured LSC for body composition in non‐ athletic populations or the LSC of each component of body composition.MethodsForty‐six adults (39 female; 7 male) partook in the study aged between 50.78 ± 15.27 years. They weighed 157.90 ± 38.83 pounds, and had a of height 64.83 ± 3 inches. Any participant who that was pregnant was excluded from the study. DXA scans for body composition and BMD was taken by the same technician. Each scan was consecutively taken 3 times, and after each scan the participant got up from the table, and was repositioned for the next scan. Results were calculated with the International Society of Clinical Densitometry's calculator.ResultsDXA scans for WB‐ Bone Area, WB‐ BMD, WB‐ Lean Mass + BMC, WB‐ Lean Mass, and WB‐ Total Mass measured less than 1% of coefficient variation, where as AP Spine BMD, WB‐ Bone Mass, WB‐Fat Mass, and WB‐% Body Fat were just over 1%, between 1.07‐ 1.3% coefficient variation. However, the WB‐ VAT Mass had a significantly higher percent (15.9%) coefficient of variation.ConclusionsDXA scans for whole body and spine all come with a 1% error as reported by DXA manufacturers, with the exception of WB VAT mass that had a significantly higher percent error.
Homocysteine Elicits an Inflammatory Profile in Murine Macrophages Through an EMMPRIN Mediated Pathway
Authors: Winchester Lee , Veeranki Sudhakar , Givvimani Srikanth , Tyagi Suresh 
Published: June 2021

IntroductionMacrophages are known to differentiate between two distinct phenotypic subsets: M1 and M2. The M1 phenotype elicits a pro‐inflammatory profile while M2 macrophages are categorized as being anti‐inflammatory. Hyperhomocysteinemia (HHcy) is associated with many inflammatory diseases such as obesity and atherosclerosis. It is known that HHcy increases specific macrophage secretory factors, such as MCP‐1 and MMP‐9. However, the direct effect of HHcy on macrophage phenotype is largely unexplored. We hypothesize that HHcy causes macrophages to shift into a more inflammatory phenotype or M1.MethodsWe utilized 2 murine macrophage cell lines: Raw 264.7 and J774A.1 cells. These cells were treated with 500 and 100 µM homocysteine, respectively, for 24 hours. Methods employed are Western Blot, ICC, FACS and PCR.ResultsIn Raw 264.7 cells, 24 hour treatment with 500 μM Hcy resulted in a 2.25 fold increase in CD40 protein expression: a cell surface marker on M1 macrophages. ICC confirms this increase in CD40. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) was also increased by 1.62 fold, indicating that MMP‐9 induction with Hcy may be through an EMMPRIN mediated pathway. J774A.1 cells were more responsive to Hcy treatment, demonstrating a 1.4 fold induction of CD40 with 24 hours of 100 μM treatment. ICC demonstrates increased MMP9 production in this cell line. We suggest that Hcy may alter IL‐1β, iNOS, TIMPs 1 and 4, and MMP‐2, as well as EMMPRIN in MMP9 production.ConclusionsOur current data suggests that Hcy treatment shifts macrophage phenotype towards the pro‐inflammatory, M1 subset. We believe that HHcy increases IL‐1 β, iNOS and MMP‐2, while demonstrating decreases in TIMPs 1 and 4.
Samchuleum suppressed high glucose‐induced renal proliferation and fibrosis in cultured rat mesangial cells
Authors: Yoon Jung Joo , Lee Yun Jung , Choi Eun Sik , Kim Mi Gyeong , Han Byung Hyuk , Kang Dae Gill , Lee Ho Sub 
Published: June 2021

Diabetic nephropathy associated with morbidity and mortality of diabetic patients. Mesangial cell proliferation is known as the major pathologic features such as glomerulosclerosis and renal fibrosis. Samchuleum (SCE), originally recorded in an ancient Korea medicinal book named “Donguibogam”, is a well‐known blended traditional herbal formula. Thus, this study was investigated the inhibitory effect of SCE (1‐50 μg/ml) on high glucose (HG)‐stimulated rat mesangial cells proliferation and fibrosis.Thymidine incorporation under HG was significantly accelerated, which was inhibited by SCE in a dose dependent manner. Pre‐treatment of SCE induced down‐regulation of cyclins/CDKs and up‐regulation of CDK inhibitor, p21waf1/cip1 and p27kip1 expression. In addition, SCE significantly suppressed the HG‐induced ROS production. Thus, SCE consequently inhibited HG‐induced mesangial cell proliferation through the inhibition of ROS signaling pathway.HG enhanced expression of ﬁbrosis biomarkers such as collagen IV and CTGF, which was markedly attenuated by SCE. Moreover, SCE inhibits HG‐induced fibronectin mRNA expression. SCE decreased TGF‐β1 and p‐Smad2/Smad4 expression, whereas increased Smad7 expression under HG. Thus, SCE promoted ECM degradation through disturbing TGF‐β–SMAD signaling.In conclusion, these results suggested that SCE has a protective effect on renal proliferation and fibrosis. Thus SCE might prove to be effective in the treatment of renal dysfunction leading to Diabetic nephropathy.
Cardiac Mechanoreceptor Activation in Humans: Evaluation by Phenylephrine and Norepinephrine
Authors: Sørensen Henrik , Ogoh Shigehiko , Sato Kohei , Siebenmann Christoph , Rasmussen Peter , Lundby Carsten , Secher Niels 
Published: June 2021

Aortic occlusion activates cardiac mechanoreceptors that elicits muscle vasodilatation and reduce heart rate (HR). Norepinephrine and phenylephrine reduce HR but whether muscle blood flow increases is not known.Cardiovascular variables were determined in males during administration of norepinephrine (n=15) or phenylephrine (n=7) and during 50° head up tilt (HUT) with and without phenylephrine (n=7). Mean arterial pressure (MAP), stroke volume (SV), HR, and total peripheral resistance (TPR) were derived by Modelflow® and near infrared spectroscopy determined biceps muscle oxygenation (SmO2).With norepinephrine MAP, SV, and TPR increased by 24 mmHg (18‐31; P<0.001; median; interquartile range), 13 ml (0‐22; P=0.026), and 3 mmHg min‐1 l‐1 (1‐4; P=0.004). HR was reduced 4 bpm (2‐7: P=0.025), while SmO2 increased 7% (3‐10; P=0.002). Similarly with phenylephrine MAP, SV, and TPR increased by 31 mmHg (22‐43; P=0.016), 18 ml (13‐24: P=0.031), and 7 mmHg min‐1 l‐1 (5‐9; P=0.016). HR was reduced by 19 bpm (17‐23; P=0.016) and SmO2 increased 7% (5‐9; P=0.016). During HUT SmO2 and SV decreased 14% (9‐14; P=0.016) and 19 ml (9‐23; P=0.031), HR increased (14 bpm; 3‐22; P=0.016), and TPR was stable. Yet, HUT phenylephrine reduces HR (15 bpm; 11‐19; P=0.016) as TPR increased (6 mmHg min‐1 l‐1 (4‐6; P=0.004) while SmO2 and SV were restored.HR decreases and TPR increases with administration of norepinephrine or phenylephrine independent of cardiac preload. Nevertheless, SmO2 increases indicating that the reduction in HR is mediated by cardiac rather than arterial mechanoreceptors when stroke volume becomes elevated.
Glia Inhibitor Blocks Ventilatory Acclimatization to Chronic Sustained Hypoxia
Authors: Stokes Jennifer , Fu Zhenxing , Powell Frank 
Published: June 2021

Neuroglial communication in the central nervous system (CNS) is proving to be an important component of neuronal signaling both in normal conditions as well as stressed or injured states. We investigated the role of CNS glial cells in neural control of ventilation during chronic hypoxia. To assess this, rats received daily administration of either minocycline, a selective microglia inhibitor, (45mg/kg) or saline (i.p.) beginning one day before and during 7 days of exposure to hypoxia (PO2 = 80 Torr). Normoxic controls, which received daily injections of either minocycline (45mg/kg) or saline, were not exposed to hypoxic conditions. Ventilation was recorded using barometric pressure plethysmography in unrestrained rats both before and after exposure to hypoxia. Daily administration of minocycline significantly (p < 0.01) decreased ventilation in normoxia and the hypoxic ventilatory response but not the hypercapnic ventilatory response, following exposure to chronic hypoxic conditions. Breathing frequency and ventilation were significantly lower in chronically hypoxic rats treated with minocycline compared to saline. Minocycline did not have an effect in normoxic conditions. Activation of microglia and astrocytes is being quantified in the NTS using immunohistochemistry. These results suggest a role for glial signaling in the physiological acclimatization during hypoxia.Supported by NIH RO1 HL‐081823
The Natriuretic Response to Acute K+ Intake
Authors: Jensen Iben , Larsen Casper , Leipziger Jens , Sørensen Mads 
Published: June 2021

IntroductionDiets rich in K+ are associated with unexplained protection against hypertension. Acute K+ intake induces natriuresis and kaliuresis in mammals linked to marked dephosphorylation of renal Na+/Cl‐‐cotransporters (NCC). Reduced activity of NCC increases Na+ delivery to the collecting ducts, hypothesized to increase driving force for ENaC‐dependent K+ secretion. Here we investigated K+ and Na+ excretion in mice adapted either to preserve or promote Na+ loss.MethodsMice were fed low (0,03%), control (0,2 % ) or high (2%) Na+ diet for 25 days. Weekly, mice received gavage of either K+ or vehicle. Mice were placed in metabolic cages and urine was collected real‐time. ENaC‐dependence of kaliuresis was assessed by benzamil injections prior to gavage.Results: 1Aldosterone and cleavage‐products of ENaC were inversely related to dietary Na+ content. 2 K+ excretion rate was reduced in mice on high Na+ diet compared to the other groups. 3 In all dietary groups, K+ load induced natiuresis and complete NCC dephosphorylation. However, maximal Na+ excretion rate was reduced 80% in Na+‐restricted and increased 15% in Na+‐loaded mice. 4 Benzamil prior to K+ loading increased natriuresis and decreased kaliuresis. Importantly, benzamil abolished all differences in kaliuresis and natriuresis between the groups.ConclusionOur data suggest that acute K+‐induced kaliuresis is completely ENaC‐dependent. Maximal K+ excretion rates are attenuated when ENaC is pharmacologically blocked or physiologically down regulated. To supply adequate luminal Na+ to the connecting tubules and the collecting ducts NCC is dephosphorylated following acute K+ load under all dietary Na+ regimes. This leads to natriuresis, even in severely Na+ restricted animals.
Participation of Immune Cells in Klotho Deficiency‐induced Salt‐sensitive Hypertension
Authors: Zhou Xiaoli , Lei Han , Sun Zhongjie 
Published: June 2021

ObjectiveKlotho (KL) is an aging‐suppressor gene. The purpose of this study is to investigate if immune cells are involved in KL deficiency‐induced salt‐sensitive hypertension.Methods & ResultsHaploinsufficiency of KL (+/‐) caused spontaneous and persistent increase in blood pressure (BP). Interestingly, the high salt (HS) intake further increased BP and exacerbated hypertension in KL(+/‐) mice, but not in WT mice, suggesting that KL deficiency elicited salt‐sensitive hypertension. The HS loading remarkably increased expression of MCP‐1 and infiltration of macrophages and T cells in kidneys in KL(+/‐) mice. Blockade of CC chemokine receptor 2 (CCR2) by a CCR2‐specific antagonist (INCB3284) abolished the HS‐induced increase in BP in KL(+/‐) mice, suggesting an important role of monocyte chemotaxis in salt‐sensitive hypertension. INCB3284 abolished infiltration of macrophages and T cells in kidneys in KL(+/‐) mice. The expression of Sgk1, NCC and ATP synthase β in kidneys was enhanced by HS loading in KL(+/‐) mice, which can be eliminated by INCB. </a> Blockade of CCR2 abolished HS‐induced renal structural damage and functional impairment in KL(+/‐) mice.ConclusionKL deficiency caused salt‐sensitive hypertension and renal damage via MCP‐1/CCR2‐mediated inflammation and infiltration of macrophages and T cells.