Gibson D. Lewis Library

Recent Research Articles from UNTHSC

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An overview of the families improving together (FIT) for weight loss randomized controlled trial in african american families.

Wed, 04/08/2015 - 7:29am

An overview of the families improving together (FIT) for weight loss randomized controlled trial in african american families.

Contemp Clin Trials. 2015 Mar 30;

Authors: Wilson DK, Kitzman-Ulrich H, Resnicow K, Lee Van Horn M, George SM, Rebekah Siceloff E, Alia KA, McDaniel T, Heatley V, Huffman L, Coulon S, Prinz R

Abstract
BACKGROUND: The Families Improving Together (FIT) randomized controlled trial tests the efficacy of integrating cultural tailoring, positive parenting, and motivational strategies into a comprehensive curriculum for weight loss in African American adolescents. The overall goal of the FIT trial is to test the effects of an integrated intervention curriculum and the added effects of a tailored web-based intervention on reducing z-BMI in overweight African American adolescents.
DESIGN AND SETTING: The FIT trial is a randomized group cohort design the will involve 520 African American families with an overweight adolescent between the ages of 11-16 years. The trial tests the efficacy of an 8-week face-to-face group randomized program comparing M+FWL (Motivational Family Weight Loss) to a comprehensive health education program (CHE) and re-randomizes participants to either an 8-week on-line tailored intervention or control on-line program resulting in a 2 (M+FWL vs. CHE group) x 2 (on-line intervention vs. control on-line program) factorial design to test the effects of the intervention on reducing z-BMI at post-treatment and at 6-month follow-up.
INTERVENTION: The interventions for this trial are based on a theoretical framework that is novel and integrates elements from cultural tailoring, Family Systems Theory, Self-Determination Theory and Social Cognitive Theory. The intervention targets positive parenting skills (parenting style, monitoring, communication); cultural values; teaching parents to increase youth motivation by encouraging youth to have input and choice (autonomy-support); and provides a framework for building skills and self-efficacy through developing weight loss action plans that target goal setting, monitoring, and positive feedback.

PMID: 25835731 [PubMed - as supplied by publisher]

Lysyl oxidases in the trabecular meshwork.

Wed, 04/08/2015 - 7:29am
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Lysyl oxidases in the trabecular meshwork.

J Glaucoma. 2014 Oct-Nov;23(8 Suppl 1):S55-8

Authors: Wordinger RJ, Clark AF

Abstract
The mechanical properties of the extracellular matrix (ECM) play an important role in maintaining cellular function and overall tissue homeostasis. Emerging evidence suggests that biomechanical modifications of the ECM may be initiators and/or drivers of disease, exemplified by increased tissue stiffness. Specific ECM cross-linking enzymes (tissue transglutaminase, lysyl oxidase, and lysyl oxidase-like 1) are expressed in the trabecular meshwork and are regulated by transforming growth factor beta (TGF-β) isoforms. As TGF-β isoforms are elevated in the aqueous humor of glaucoma patients, trabecular meshwork stiffness mediated by ECM cross-linking may be responsible for increased aqueous humor outflow resistance and elevated intraocular pressure.

PMID: 25275908 [PubMed - indexed for MEDLINE]

Evaluation of a novel material, Diomics X-Swab™, for collection of DNA.

Wed, 04/08/2015 - 7:29am
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Evaluation of a novel material, Diomics X-Swab™, for collection of DNA.

Forensic Sci Int Genet. 2014 Sep;12:192-8

Authors: Marshall PL, Stoljarova M, Larue BL, King JL, Budowle B

Abstract
Success of DNA typing is related to the amount of target material recovered from an evidentiary item. Generally, the more DNA that is recovered, the better the chance is of obtaining a typing result that will be robust and reliable. One method of collecting stain materials is by swabbing. Recovery of DNA from a number of commercially available swabs is not an efficient process. The X-Swab™ (Diomics Corporation, La Jolla, CA) is a unique bio-specimen collection material with highly absorptive properties and can be dissolved during certain extraction conditions. Therefore, more DNA may be collected from a substrate and be released from the swab matrix than other swabs. The ability to recover DNA from X-Swab material and success in STR typing were compared with the Copan 4N6FLOQSwab™ (Brescia, Italy), a device which utilizes a proprietary flocked-swab technology to maximize DNA collection and elution efficiency. Both types of swabs were impregnated with known amounts of DNA and body fluids and allowed to air dry. In addition, blood was placed onto glass slides, allowed to dry and collected using both types of swabs. DNA recovery was assessed by DNA quantitation and by STR typing. Results suggested that X-Swab material yielded greater DNA recovery, particularly of low quantity samples (defined as diluted neat samples), compared with the 4N6FLOQSwab. Results also indicated that X-Swab material itself enhances yield of PCR products.

PMID: 25016249 [PubMed - indexed for MEDLINE]

A high volume extraction and purification method for recovering DNA from human bone.

Wed, 04/08/2015 - 7:29am
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A high volume extraction and purification method for recovering DNA from human bone.

Forensic Sci Int Genet. 2014 Sep;12:155-60

Authors: Marshall PL, Stoljarova M, Schmedes SE, King JL, Budowle B

Abstract
DNA recovery, purity and overall extraction efficiency of a protocol employing a novel silica-based column, Hi-Flow(®) (Generon Ltd., Maidenhead, UK), were compared with that of a standard organic DNA extraction methodology. The quantities of DNA recovered by each method were compared by real-time PCR and quality of DNA by STR typing using the PowerPlex(®) ESI 17 Pro System (Promega Corporation, Madison, WI) on DNA from 10 human bone samples. Overall, the Hi-Flow method recovered comparable quantities of DNA ranging from 0.8ng±1 to 900ng±159 of DNA compared with the organic method ranging from 0.5ng±0.9 to 855ng±156 of DNA. Complete profiles (17/17 loci tested) were obtained for at least one of three replicates for 3/10 samples using the Hi-Flow method and from 2/10 samples with the organic method. All remaining bone samples yielded partial profiles for all replicates with both methods. Compared with a standard organic DNA isolation method, the results indicated that the Hi-Flow method provided equal or improved recovery and quality of DNA without the harmful effects of organic extraction. Moreover, larger extraction volumes (up to 20mL) can be employed with the Hi-Flow method which enabled more bone sample to be extracted at one time.

PMID: 24997320 [PubMed - indexed for MEDLINE]

High-quality and high-throughput massively parallel sequencing of the human mitochondrial genome using the Illumina MiSeq.

Wed, 04/08/2015 - 7:29am
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High-quality and high-throughput massively parallel sequencing of the human mitochondrial genome using the Illumina MiSeq.

Forensic Sci Int Genet. 2014 Sep;12:128-35

Authors: King JL, LaRue BL, Novroski NM, Stoljarova M, Seo SB, Zeng X, Warshauer DH, Davis CP, Parson W, Sajantila A, Budowle B

Abstract
Mitochondrial DNA typing in forensic genetics has been performed traditionally using Sanger-type sequencing. Consequently sequencing of a relatively-large target such as the mitochondrial genome (mtGenome) is laborious and time consuming. Thus, sequencing typically focuses on the control region due to its high concentration of variation. Massively parallel sequencing (MPS) has become more accessible in recent years allowing for high-throughput processing of large target areas. In this study, Nextera(®) XT DNA Sample Preparation Kit and the Illumina MiSeq™ were utilized to generate quality whole genome mitochondrial haplotypes from 283 individuals in a both cost-effective and rapid manner. Results showed that haplotypes can be generated at a high depth of coverage with limited strand bias. The distribution of variants across the mitochondrial genome was described and demonstrated greater variation within the coding region than the non-coding region. Haplotype and haplogroup diversity were described with respect to whole mtGenome and HVI/HVII. An overall increase in haplotype or genetic diversity and random match probability, as well as better haplogroup assignment demonstrates that MPS of the mtGenome using the Illumina MiSeq system is a viable and reliable methodology.

PMID: 24973578 [PubMed - indexed for MEDLINE]

Population data on 25 autosomal STRs for 500 unrelated Kuwaitis.

Wed, 04/08/2015 - 7:29am
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Population data on 25 autosomal STRs for 500 unrelated Kuwaitis.

Forensic Sci Int Genet. 2014 Sep;12:126-7

Authors: Al-Enizi M, Ge J, Salih A, Alenizi H, Al Jabber J, Ziab J, Al Harbi E, Isameal S, Budowle B

PMID: 24960412 [PubMed - indexed for MEDLINE]

mitoSAVE: mitochondrial sequence analysis of variants in Excel.

Wed, 04/08/2015 - 7:29am
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mitoSAVE: mitochondrial sequence analysis of variants in Excel.

Forensic Sci Int Genet. 2014 Sep;12:122-5

Authors: King JL, Sajantila A, Budowle B

Abstract
The mitochondrial genome (mtGenome) contains genetic information amenable to numerous applications such as medical research, population and evolutionary studies, and human identity testing. However, inconsistent nomenclature assignment makes haplotype comparison difficult and can lead to false exclusion of potentially useful profiles. Massively Parallel Sequencing (MPS) is a platform for sequencing large datasets and potentially whole populations with relative ease. However, the data generated are not easily parsed and interpreted. With this in mind, mitoSAVE has been developed to enable fast conversion of Variant Call Format (VCF) files. mitoSAVE is an Excel-based workbook that converts data within the VCF into mtDNA haplotypes using phylogenetically-established nomenclature as well as rule-based alignments consistent with current forensic standards. mitoSAVE is formatted for human mitochondrial genome; however, it can easily be adapted to support other reasonably small genomes.

PMID: 24952129 [PubMed - indexed for MEDLINE]

Genetic and linguistic correlation of the Kra-Dai-speaking groups in Thailand.

Sat, 04/04/2015 - 3:30am

Genetic and linguistic correlation of the Kra-Dai-speaking groups in Thailand.

J Hum Genet. 2015 Apr 2;

Authors: Srithawong S, Srikummool M, Pittayaporn P, Ghirotto S, Chantawannakul P, Sun J, Eisenberg A, Chakraborty R, Kutanan W

Abstract
The Kra-Dai linguistic family includes Thai and Lao as well as a great number of languages spoken by ethnic minorities in Southeast Asia. In Thailand, a dozen of other Kra-Dai languages are spoken in addition to Thai, the national language. The genetic structure of the Kra-Dai-speaking populations in Thailand has been studied extensively using uniparentally inherited markers. To extend this line of genetic investigation, this study used 15 autosomal microsatellites of 500 individuals from 11 populations, belonging to nine Kra-Dai ethnicities, namely, the Kaleung, Phu Thai, Saek, Nyo, Lao Isan, Yuan, Black Tai, Phuan and Lue. These ethnolinguistic groups are dispersed in three different geographic regions of Thailand, that is, Northern, Northeastern and Central. The results show a very low average of pairwised Fst (0.0099), as well as no population substructure based on STRUCTURE analysis, indicating genetic homogeneity within the Kra-Dai-speaking group, possibly owing to shared linguistic ancestry. The Mantel test, an analysis of molecular variance, and the approximate Bayesian computation procedure employed to evaluate potential factors for driving genetic diversity revealed that language is the predominant factor affecting genetic variations, whereas geography is not. The result of distance-based clustering analyses and spatial analysis of molecular variance revealed genetic distinctions of some populations, reflecting the effects of genetic drift and gene flow on allele frequency within populations, in concordance with the result of R-matrix regression. The genetic and linguistic affiliations of the contemporary Kra-Dai-speaking groups are consistent with each other despite certain deviation due to various evolutionary factors that may have occurred during their migrations and resettlements.Journal of Human Genetics advance online publication, 2 April 2015; doi:10.1038/jhg.2015.32.

PMID: 25833471 [PubMed - as supplied by publisher]

Amiloride and GMQ allosteric modulation of the GABA-A ρ1 receptor: influences of the intersubunit site.

Fri, 04/03/2015 - 3:29am

Amiloride and GMQ allosteric modulation of the GABA-A ρ1 receptor: influences of the intersubunit site.

J Pharmacol Exp Ther. 2015 Mar 31;

Authors: Snell HD, Gonzales EB

Abstract
Amiloride, a diuretic used in the treatment of hypertension and congestive heart failure, and 2-guanidine-4-methylquinazoline (GMQ), are guanidine compounds that modulate acid-sensing ion channels. Both compounds have demonstrated affinity for a variety of membrane proteins, including members of the Cys-loop family of ligand-gated ion channels, such as the heteromeric GABA-A αβγ receptors. The actions of these guanidine compounds on the homomeric GABA-A ρ1 receptor remains unclear, especially in light of how many GABA-A αβγ receptor modulators have different effects in the GABA-A ρ1 receptors. We sought to characterize the influence of amiloride and 2-guanidine-4-methyquinazoline (GMQ) on the human GABA-A ρ1 receptors using whole-cell patch clamp electrophysiology. The diuretic amiloride potentiated the human GABA-A ρ1 GABA-mediated current, while GMQ antagonized the receptor. Furthermore, a GABA-A second transmembrane domain site, the intersubunit site, responsible for allosteric modulation in the heteromeric GABA-A receptors, mediated amiloride's positive allosteric actions. In contrast, the mutation did not remove GMQ antagonism but only changed the guanidine compound's potency within the human GABA-A ρ1 receptor. Through modeling and introduction of point mutations, we propose that the GABA-A ρ1 intersubunit site plays a role in mediating the allosteric effects of amiloride and GMQ.

PMID: 25829529 [PubMed - as supplied by publisher]

Neuronal injury from cardiac arrest: aging years in minutes.

Thu, 04/02/2015 - 3:29am
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Neuronal injury from cardiac arrest: aging years in minutes.

Age (Dordr). 2014;36(4):9680

Authors: Cherry BH, Sumien N, Mallet RT

Abstract
Cardiac arrest is a leading cause of death and permanent disability. Most victims succumb to the oxidative and inflammatory damage sustained during cardiac arrest/resuscitation, but even survivors typically battle long-term neurocognitive impairment. Although extensive research has delineated the complex mechanisms that culminate in neuronal damage and death, no effective treatments have been developed to interrupt these mechanisms. Of importance, many of these injury cascades are also active in the aging brain, where neurons and other cells are under persistent oxidative and inflammatory stress which eventually damages or kills the cells. In light of these similarities, it is reasonable to propose that the brain essentially ages the equivalent of several years within the few minutes taken to resuscitate a patient from cardiac arrest. Accordingly, cardiac arrest-resuscitation models may afford an opportunity to study the deleterious mechanisms underlying the aging process, on an accelerated time course. The aging and resuscitation fields both stand to gain pivotal insights from one another regarding the mechanisms of injury sustained during resuscitation from cardiac arrest and during aging. This synergism between the two fields could be harnessed to foster development of treatments to not only save lives but also to enhance the quality of life for the elderly.

PMID: 25104136 [PubMed - indexed for MEDLINE]

ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning.

Thu, 04/02/2015 - 3:29am
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ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning.

Age (Dordr). 2014;36(4):9685

Authors: Su C, Sun F, Cunningham RL, Rybalchenko N, Singh M

Abstract
Oxidative stress has long been implicated in the pathogenesis of various neurodegenerative disorders such as Alzheimer's disease and stroke. While high levels of oxidative stress are generally associated with cell death, a slight rise of reactive oxygen species (ROS) levels can be protective by "preconditioning" cells to develop a resistance against subsequent challenges. However, the mechanisms underlying such preconditioning (PC)-induced protection are still poorly understood. Previous studies have supported a role of ERK5 (mitogen-activated protein [MAP] kinase 5) in neuroprotection and ischemic tolerance in the hippocampus. In agreement with these findings, our data suggest that ERK5 mediates both hydrogen peroxide (H2O2)-induced PC as well as nerve growth factor (NGF)-induced neuroprotection. Activation of ERK5 partially rescued pheochromocytoma PC12 cells as well as primary hippocampal neurons from H2O2-caused death, while inhibition of ERK5 abolished NGF or PC-induced protection. These results implicate ERK5 signaling as a common downstream pathway for NGF and PC. Furthermore, both NGF and PC increased the expression of the transcription factor, KLF4, which can initiate an anti-apoptotic response in various cell types. Induction of KLF4 by NGF or PC was blocked by siERK5, suggesting that ERK5 is required in this process. siKLF4 can also attenuate NGF- or PC-induced neuroprotection. Overexpression of active MEK5 or KLF4 in H2O2-stressed cells increased Bcl-2/Bax ratio and the expression of NAIP (neuronal apoptosis inhibitory protein). Taken together, our data suggest that ERK5/KLF4 cascade is a common signaling pathway shared by at least two important mechanisms by which neurons can be protected from cell death.

PMID: 25015774 [PubMed - indexed for MEDLINE]

Cerebral palsy of the elbow and forearm.

Thu, 04/02/2015 - 3:29am
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Cerebral palsy of the elbow and forearm.

J Hand Surg Am. 2014 Jul;39(7):1425-32

Authors: Bunata R, Icenogle K

Abstract
Management of elbow and forearm involvement in cerebral palsy has evolved over the last 3 decades with a better understanding of its neuropathophysiology, improved outcome measures, and evolving therapy protocols. Current nonoperative and surgical treatment methods are discussed. The use of standard function measuring instruments and encouragement of the participation in research will hopefully result in more accurate outcome information and, thereby, refine our techniques and rehabilitation methods.

PMID: 24969499 [PubMed - indexed for MEDLINE]

Interaction of astrocytes and T cells in physiological and pathological conditions.

Wed, 04/01/2015 - 3:29am

Interaction of astrocytes and T cells in physiological and pathological conditions.

Brain Res. 2015 Mar 23;

Authors: Xie L, Yang SH

Abstract
The central nervous system (CNS) has long been recognized as a site of 'immune privilege' because of the existence of the blood brain barrier (BBB) which presumably isolates CNS from the peripheral immunosurveillance. Different from the peripheral organs, CNS is unique in response to all forms of CNS injury and disease which is mainly mediated by resident microglia and astrocyte. There is increasing evidence that immune cells are not only involved in neuroinflammation process but also the maintenance of CNS homeostasis. T cells, an important immune cell population, are involved in the pathogenesis of some neurological diseases by inducing either innate or adaptive immune responses. Astrocytes, which are the most abundant cell type in the CNS, maintain the integrity of BBB and actively participate in the initiation and progression of neurological diseases. Surprisingly, how astrocytes and T cells interact and the consequences of their interaction are not clear. In this review we briefly summarized T cells diversity and astrocyte function. Then, we examined the evidence for the astrocytes and T cells interaction under physiological and pathological conditions including ischemic stroke, multiple sclerosis, viral infection, and Alzheimer's disease. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.

PMID: 25813828 [PubMed - as supplied by publisher]

Pulmonary arterial hypertension in adults: novel drugs and catheter ablation techniques show promise? Systematic review on pharmacotherapy and interventional strategies.

Wed, 04/01/2015 - 3:29am
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Pulmonary arterial hypertension in adults: novel drugs and catheter ablation techniques show promise? Systematic review on pharmacotherapy and interventional strategies.

Biomed Res Int. 2014;2014:743868

Authors: Rosanio S, Pelliccia F, Gaudio C, Greco C, Keylani AM, D'Agostino DC

Abstract
This systematic review aims to provide an update on pharmacological and interventional strategies for the treatment of pulmonary arterial hypertension in adults. Currently US Food and Drug Administration approved drugs including prostanoids, endothelin-receptor antagonists, phosphodiesterase type-5 inhibitors, and soluble guanylate-cyclase stimulators. These agents have transformed the prognosis for pulmonary arterial hypertension patients from symptomatic improvements in exercise tolerance ten years ago to delayed disease progression today. On the other hand, percutaneous balloon atrioseptostomy by using radiofrequency perforation, cutting balloon dilatation, or insertion of butterfly stents and pulmonary artery catheter-based denervation, both associated with very low rate of major complications and death, should be considered in combination with specific drugs at an earlier stage rather than late in the progression of pulmonary arterial hypertension and before the occurrence of overt right-sided heart failure.

PMID: 25013799 [PubMed - indexed for MEDLINE]

Hypertrophic cardiomyopathy associated Lys104Glu mutation in the myosin regulatory light chain causes diastolic disturbance in mice.

Wed, 04/01/2015 - 3:29am
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Hypertrophic cardiomyopathy associated Lys104Glu mutation in the myosin regulatory light chain causes diastolic disturbance in mice.

J Mol Cell Cardiol. 2014 Sep;74:318-29

Authors: Huang W, Liang J, Kazmierczak K, Muthu P, Duggal D, Farman GP, Sorensen L, Pozios I, Abraham TP, Moore JR, Borejdo J, Szczesna-Cordary D

Abstract
We have examined, for the first time, the effects of the familial hypertrophic cardiomyopathy (HCM)-associated Lys104Glu mutation in the myosin regulatory light chain (RLC). Transgenic mice expressing the Lys104Glu substitution (Tg-MUT) were generated and the results were compared to Tg-WT (wild-type human ventricular RLC) mice. Echocardiography with pulse wave Doppler in 6month-old Tg-MUT showed early signs of diastolic disturbance with significantly reduced E/A transmitral velocities ratio. Invasive hemodynamics in 6month-old Tg-MUT mice also demonstrated a borderline significant prolonged isovolumic relaxation time (Tau) and a tendency for slower rate of pressure decline, suggesting alterations in diastolic function in Tg-MUT. Six month-old mutant animals had no LV hypertrophy; however, at >13months they displayed significant hypertrophy and fibrosis. In skinned papillary muscles from 5 to 6month-old mice a mutation induced reduction in maximal tension and slower muscle relaxation rates were observed. Mutated cross-bridges showed increased rates of binding to the thin filaments and a faster rate of the power stroke. In addition, ~2-fold lower level of RLC phosphorylation was observed in the mutant compared to Tg-WT. In line with the higher mitochondrial content seen in Tg-MUT hearts, the MUT-myosin ATPase activity was significantly higher than WT-myosin, indicating increased energy consumption. In the in vitro motility assay, MUT-myosin produced higher actin sliding velocity under zero load, but the velocity drastically decreased with applied load in the MUT vs. WT myosin. Our results suggest that diastolic disturbance (impaired muscle relaxation, lower E/A) and inefficiency of energy use (reduced contractile force and faster ATP consumption) may underlie the Lys104Glu-mediated HCM phenotype.

PMID: 24992035 [PubMed - indexed for MEDLINE]

Methamphetamine and HIV-1-induced neurotoxicity: role of trace amine associated receptor 1 cAMP signaling in astrocytes.

Wed, 04/01/2015 - 3:29am
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Methamphetamine and HIV-1-induced neurotoxicity: role of trace amine associated receptor 1 cAMP signaling in astrocytes.

Neuropharmacology. 2014 Oct;85:499-507

Authors: Cisneros IE, Ghorpade A

Abstract
Methamphetamine (METH) is abused by about 5% of the United States population with approximately 10-15% of human immunodeficiency virus-1 (HIV-1) patients reporting its use. METH abuse accelerates the onset and severity of HIV-associated neurocognitive disorders (HAND) and astrocyte-induced neurotoxicity. METH activates G-protein coupled receptors such as trace amine associated receptor 1 (TAAR1) increasing intracellular cyclic adenosine monophosphate (cAMP) levels in presynaptic cells of monoaminergic systems. In the present study, we investigated the effects of METH and HIV-1 on primary human astrocyte TAAR1 expression, function and glutamate clearance. Our results demonstrate combined conditions increased TAAR1 mRNA levels 7-fold and increased intracellular cAMP levels. METH and beta-phenylethylamine (β-PEA), known TAAR1 agonists, increased intracellular cAMP levels in astrocytes. Further, TAAR1 knockdown significantly reduced intracellular cAMP levels in response to METH/β-PEA, indicating signaling through astrocyte TAAR1. METH±HIV-1 decreased excitatory amino acid transporter-2 (EAAT-2) mRNA and significantly decreased glutamate clearance. RNA interference for TAAR1 prevented METH-mediated decreases in EAAT-2. TAAR1 knockdown significantly increased glutamate clearance, which was further heightened significantly by METH. Moreover, TAAR1 overexpression significantly decreased EAAT-2 levels and glutamate clearance that were further reduced by METH. Taken together, our data show that METH treatment activated TAAR1 leading to intracellular cAMP in human astrocytes and modulated glutamate clearance abilities. Furthermore, molecular alterations in astrocyte TAAR1 levels correspond to changes in astrocyte EAAT-2 levels and function. To our knowledge this is the first report implicating astrocyte TAAR1 as a novel receptor for METH during combined injury in the context of HAND.

PMID: 24950453 [PubMed - indexed for MEDLINE]

Trileaflet Mitral Valve with Three Papillary Muscles Associated with Hypertrophic Cardiomyopathy: A Novel Case.

Tue, 03/31/2015 - 3:30am

Trileaflet Mitral Valve with Three Papillary Muscles Associated with Hypertrophic Cardiomyopathy: A Novel Case.

Echocardiography. 2015 Mar 25;

Authors: Rosanio S, Simonsen CJ, Starwalt J, Keylani AM, Vitarelli A

Abstract
Congenital mitral valve (MV) malformations are uncommon, except for MV prolapse. Despite their infrequency, most of them are well-known and defined entities, such as congenital MV stenosis with two papillary muscles, parachute MV, supravalvular mitral ring, hypoplastic MV, isolated cleft in the anterior and/or posterior leaflets, and double-orifice MV. A trileaflet MV with three separate papillary muscles with concordant atrioventricular and ventricle-arterial connections is exceptionally rare. To the best of the authors' knowledge, it has been reported only once in association with subaortic valvular stenosis. We hereby describe a novel case associated with hypertrophic cardiomyopathy.

PMID: 25809503 [PubMed - as supplied by publisher]

Downregulation of Aquaporin 4 Expression through Extracellular Signal-regulated Kinases1/2 Activation in Cultured Astrocytes Following Scratch-injury.

Fri, 03/27/2015 - 3:29am

Downregulation of Aquaporin 4 Expression through Extracellular Signal-regulated Kinases1/2 Activation in Cultured Astrocytes Following Scratch-injury.

Biomed Environ Sci. 2015 Mar;28(3):199-205

Authors: Shi ZF, Zhao WJ, Xu LX, Dong LP, Yang SH, Yuan F

Abstract
OBJECTIVE: To investigate the role of extracellular signal-regulated kinase1/2 (ERK1/2) pathway in the regulation of aquaporin 4 (AQP4) expression in cultured astrocytes after scratch-injury.
METHODS: The scratch-injury model was produced in cultured astrocytes of rat by a 10-μL plastic pipette tip. The morphological changes of astrocytes and lactate dehydrogenase (LDH) leakages were observed to assess the degree of scratch-injury. AQP4 expression was detected by immunofluorescence staining and Western blot, and phosphorylated-ERK1/2 (p-ERK1/2) expression was determined by Western blot. To explore the effect of ERK1/2 pathway on AQP4 expression in scratch-injured astrocytes, 10 µmol/L U0126 (ERK1/2 inhibitor) was incubated in the medium at 30 min before the scratch-injury in some groups.
RESULTS: Increases in LDH leakage were observed at 1, 12, and 24 h after scratch-injury, and AQP4 expression was reduced simultaneously. Decrease in AQP4 expression was associated with a significant increase in ERK1/2 activation. Furthermore, pretreatment with U0126 blocked both ERK1/2 activation and decrease in AQP4 expression induced by scratch-injury.
CONCLUSION: These results indicate that ERK1/2 pathway down-regulates AQP4 expression in scratch-injured astrocytes, and ERK1/2 pathway might be a novel therapeutic target in reversing the effects of astrocytes that contribute to traumatic brain edema.

PMID: 25800444 [PubMed - in process]

Chip-based nanoelectrospray ionization with Fourier transform mass spectrometric detection to screen for local anesthetics intended to mask limb sore in walking horses.

Fri, 03/27/2015 - 3:29am

Chip-based nanoelectrospray ionization with Fourier transform mass spectrometric detection to screen for local anesthetics intended to mask limb sore in walking horses.

J Mass Spectrom. 2015 Mar;50(3):533-7

Authors: Szarka S, Prokai L

Abstract
We report a high-throughput chip-based nanoelectrospray ionization method coupled with Fourier transform mass spectrometry to screen for local anesthetics in samples collected by swabbing. These drugs have been used to mask pain on the limbs of walking horses after forbidden practices of soring or physical abuse. Optimized for lidocaine, the method afforded sub-ppm mass accuracy for nine local anesthetics included in the study. From doped cotton swabs, two third and all of the analytes were detected after adding 10 ng and 100 ng of each drug, respectively. Benzocaine and/or lidocaine were found on positive swab samples collected during walking horse competitions. Copyright © 2015 John Wiley & Sons, Ltd.

PMID: 25800188 [PubMed - in process]

Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10.

Fri, 03/27/2015 - 3:29am
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Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10.

Eur J Immunol. 2015 Jan;45(1):180-91

Authors: Xie L, Choudhury GR, Winters A, Yang SH, Jin K

Abstract
Forkhead box P3 (Foxp3)(+) regulatory T (Treg) cells maintain the immune tolerance and prevent inflammatory responses in the periphery. However, the presence of Treg cells in the CNS under steady state has not been studied. Here, for the first time, we show a substantial TCRαβ (+) CD4(+) Foxp3(+) T-cell population (cerebral Treg cells) in the rat cerebrum, constituting more than 15% of the cerebral CD4(+) T-cell compartment. Cerebral Treg cells showed an activated/memory phenotype and expressed many Treg-cell signature genes at higher levels than peripheral Treg cells. Consistent with their activated/memory phenotype, cerebral Treg cells robustly restrained the LPS-induced inflammatory responses of brain microglia/macrophages, suggesting a role in maintaining the cerebral homeostasis by inhibiting the neuroinflammation. In addition, brain astrocytes were the helper cells that sustained Foxp3 expression in Treg cells through IL-2/STAT5 signaling, showing that the interaction between astrocytes and Treg cells contributes to the maintenance of Treg-cell identity in the brain. Taken together, our work represents the first study to characterize the phenotypic and functional features of Treg cells in the rat cerebrum. Our data have provided a novel insight for the contribution of Treg cells to the immunosurveillance and immunomodulation in the cerebrum under steady state.

PMID: 25329858 [PubMed - indexed for MEDLINE]

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