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https://www.readbyqxmd.com/read/28300083/mr-guided-parenchymal-delivery-of-adeno-associated-viral-vector-serotype-5-in-non-human-primate-brain
#1
L Samaranch, B Blits, W San Sebastian, P Hadaczek, J Bringas, V Sudhakar, M Macayan, P J Pivirotto, H Petry, K S Bankiewicz
The present study was designed to characterize transduction of non-human primate brain and spinal cord with AAV5 viral vector after parenchymal delivery. AAV5-CAG-GFP (1 × 10(13) vector genomes per milliliter (vg ml(-1))) was bilaterally infused either into putamen, thalamus or with the combination left putamen and right thalamus. Robust expression of GFP was seen throughout infusion sites and also in other distal nuclei. Interestingly, thalamic infusion of AAV5 resulted in the transduction of the entire corticospinal axis, indicating transport of AAV5 over long distances...
March 16, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28295444/the-polymorphic-cag-repeat-in-exon1-of-androgen-receptor-is-associated-with-level-of-hdl-cholesterol-and-hypertension-in-chinese-middle-aged-to-elderly-men
#2
Deyu Yang, Jinhai Tian, Xu Zhang, Jingjing Yu, Shuya Li, Zhizhong Wang, Yuying Ma, Lan Liu, Qi Huang, Rong Ma, Jia Wang, Xin Li, Min Jiang
OBJECTIVE: The length of the CAG repeats in exon 1 of the androgen receptor (AR) gene has been shown to be inversely correlated with AR transcriptional activity. This study aimed to investigate the correlations between the length of CAG repeat in AR and serum lipids and hypertension in Chinese men. DESIGN AND PATIENTS: The relationship between length of the CAG repeat in exon 1 of AR with prevalence ofhypertension and the levels of serum lipids among Chinese men(aged ≥ 40 years)...
March 10, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28295144/androgen-receptor-polyglutamine-repeat-length-ar-cagn-modulates-the-effect-of-testosterone-on-androgen-associated-somatic-traits-in-filipino-young-adult-men
#3
Calen P Ryan, Alexander V Georgiev, Thomas W McDade, Lee T Gettler, Dan T A Eisenberg, Margarita Rzhetskaya, Sonny S Agustin, M Geoffrey Hayes, Christopher W Kuzawa
OBJECTIVES: The androgen receptor (AR) mediates expression of androgen-associated somatic traits such as muscle mass and strength. Within the human AR is a highly variable glutamine short-tandem repeat (AR-CAGn), and CAG repeat number has been inversely correlated to AR transcriptional activity in vitro. However, evidence for an attenuating effect of long AR-CAGn on androgen-associated somatic traits has been inconsistent in human populations. One possible explanation for this lack of consistency is that the effect of AR-CAGn on AR bioactivity in target tissues likely varies in relation to circulating androgen levels...
March 14, 2017: American Journal of Physical Anthropology
https://www.readbyqxmd.com/read/28293234/dysbiosis-of-gut-microbiota-associated-with-clinical-parameters-in-polycystic-ovary-syndrome
#4
Rui Liu, Chenhong Zhang, Yu Shi, Feng Zhang, Linxia Li, Xuejiao Wang, Yunxia Ling, Huaqing Fu, Weiping Dong, Jian Shen, Andrew Reeves, Andrew S Greenberg, Liping Zhao, Yongde Peng, Xiaoying Ding
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. Gut microbiota has been implicated to play a critical role in metabolic diseases and may modulate the secretion of mediators of the brain-gut axis. Interaction between gut microbiota and the endocrine and biochemical disturbances in PCOS still remains elusive. Here, we showed an altered gut microbiota significantly correlated with PCOS phenotype. There were 33 patients with PCOS (non-obese PCOS individuals, PN, n = 12; obese PCOS individuals, PO, n = 21) as well as 15 control subjects (non-obese control individuals, CN, n = 9; obese control individuals, CO, n = 6) enrolled in our study...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28290732/cycloastragenol-mediates-activation-and-proliferation-suppression-in-concanavalin-a-induced-mouse-lymphocyte-pan-activation-model
#5
Chenghong Sun, Mingmin Jiang, Li Zhang, Jian Yang, Guimin Zhang, Bingyuan Du, Yushan Ren, Xin Li, Jingchun Yao
CONTEXT: Cycloastragenol (CAG) is a molecule isolated from various species in the genus Astragalus. Although the regulatory activity of Astragalus on immune system has been investigated, the effect of CAG on activated lymphocytes is poorly understood. OBJECTIVE: We aimed to biologically address the possible anti-inflammation potential of CAG on concanavalin A (Con A)-mediated mouse lymphocyte pan-activation model. MATERIALS AND METHODS: Mouse lymphocytes were obtained from spleens and subjected to Con A for 24 h...
March 14, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28287537/visualization-of-cell-cycle-variations-and-determination-of-nucleation-in-postnatal-cardiomyocytes
#6
Alexandra Raulf, Nadine Voeltz, Daniel Korzus, Bernd K Fleischmann, Michael Hesse
Cardiomyocytes are prone to variations of the cell cycle, such as endoreduplication (continuing rounds of DNA synthesis without karyokinesis and cytokinesis) and acytokinetic mitosis (karyokinesis but no cytokinesis). Such atypical cell cycle variations result in polyploid and multinucleated cells rather than in cell division. Therefore, to determine cardiac turnover and regeneration, it is of crucial importance to correctly identify cardiomyocyte nuclei, the number of nuclei per cell, and their cell cycle status...
February 24, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28286572/attenuation-of-helicobacter-pylori-induced-gastric-inflammation-by-prior-cag-strain-am1-infection-in-c57bl-6-mice
#7
Nillu Ghosh, Prachetash Ghosh, Kousik Kesh, Asish K Mukhopadhyay, Snehasikta Swarnakar
BACKGROUND: Helicobacter pylori, colonize in stomach of ~50% of the world population. cag pathogenicity Island of H. pylori is one of the important virulent factors that attributed to gastric inflammation. Coinfection with H. pylori strain with different genetic makeup alters the degree of pathogenicity and susceptibility towards antibiotics. The present study investigates host immunomodulatory effects of H. pylori infection by both cag(+) strain (SS1) and cag(-) strain (AM1). C57BL/6 mice were infected with AM1 or SS1 strain as well as AM1 followed by SS1 (AM1/SS1) and vice versa...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/28286179/formation-of-hippocampal-mhtt-aggregates-leads-to-impaired-spatial-memory-hippocampal-activation-and-adult-neurogenesis
#8
L C Schwab, K Richetin, R A Barker, N Déglon
Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by a triad of motor, psychiatric and cognitive deficits with the latter classically attributed to disruption of fronto-striatal circuits. However, emerging evidence suggests that some of the cognitive deficits in HD may have their origin in other structures including the hippocampus. Hippocampal abnormalities have been reported in HD mouse models particularly in terms of performance on the Morris Water Maze. However, in these animals, it is difficult to be certain whether the spatial memory deficits are due to local pathology within this structure or their poor mobility and motivation...
March 9, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28270748/huntingtin-is-required-for-neural-but-not-cardiac-pancreatic-progenitor-differentiation-of-mouse-embryonic-stem-cells-in-vitro
#9
Man Shan Yu, Naoko Tanese
Mutation in the huntingtin (HTT) gene causes Huntington's disease (HD). It is an autosomal dominant trinucleotide-repeat expansion disease in which CAG repeat sequence expands to >35. This results in the production of mutant HTT protein with an increased stretch of glutamines near the N-terminus. The wild type HTT gene encodes a 350 kD protein whose function remains elusive. Mutant HTT protein has been implicated in transcription, axonal transport, cytoskeletal structure/function, signal transduction, and autophagy...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28266655/intact-sensory-motor-network-structure-and-function-in-far-from-onset-premanifest-huntington-s-disease
#10
Martin Gorges, Hans-Peter Müller, Isabella Maria Sophie Mayer, Gesa Sophie Grupe, Thomas Kammer, Georg Grön, Jan Kassubek, G Bernhard Landwehrmeyer, Robert Christian Wolf, Michael Orth
Structural and functional changes attributable to the neurodegenerative process in Huntington's disease (HD) may be evident in HTT CAG repeat expansion carriers before the clinical manifestations of HD. It remains unclear, though, how far from motor onset a consistent signature of the neurodegenerative process in HD can be detected. Twelve far from onset preHD and 22 age-matched healthy control participants underwent volumetric structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI (11 preHD, 22 controls) as well as electrophysiological measurements (12 preHD, 13 controls)...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28265888/huntington-disease-linking-pathogenesis-to-the-development-of-experimental-therapeutics
#11
REVIEW
Tiago A Mestre, Cristina Sampaio
Huntington disease (HD) is an autosomal dominant neurodegenerative condition caused by a CAG trinucleotide expansion in the huntingtin gene. At present, the HD field is experiencing exciting times with the assessment for the first time in human subjects of interventions aimed at core disease mechanisms. Out of a portfolio of interventions that claim a potential disease-modifying effect in HD, the target huntingtin has more robust validation. In this review, we discuss the spectrum of huntingtin-lowering therapies that are currently being considered...
February 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28263872/evidence-of-oxidative-stress-and-mitochondrial-dysfunction-in-spinocerebellar-ataxia-type-2-sca2-patient-fibroblasts-effect-of-coenzyme-q10-supplementation-on-these-parameters
#12
Nanna Cornelius, Jonathan H Wardman, Iain P Hargreaves, Viruna Neergheen, Anne Sigaard Bie, Zeynep Tümer, Jørgen E Nielsen, Troels T Nielsen
Spinocerebellar ataxia type 2 (SCA2) is a rare neurodegenerative disorder caused by a CAG repeat expansion in the ataxin-2 gene. We show increased oxidative stress, abnormalities in the antioxidant system, changes in complexes involved in oxidative phosphorylation and changes in mitochondrial morphology in SCA2 patient fibroblasts compared to controls, and we show that treatment with CoQ10 can partially reverse these changes. Together, our results suggest that oxidative stress and mitochondrial dysfunction may be contributory factors to the pathophysiology of SCA2 and that therapeutic strategies involving manipulation of the antioxidant system could prove to be of clinical benefit...
March 2, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28255235/high-coronary-calcium-score-and-post-procedural-ck-mb-are-noninvasive-predictors-of-coronary-stent-restenosis
#13
Jae-Beom Lee, Yun-Seok Choi, Woo-Baek Chung, Ami Kwon, Chul-Soo Park, Man-Young Lee
PURPOSE: High coronary calcium score (CCS) and post-procedural cardiac enzyme may be related with poor outcomes in patients with coronary stent implantation. METHODS: A total of 1,072 patients (63.2% male, mean age: 61.7±10.3 years) who underwent coronary multi-detect computed tomography at index procedure and follow-up coronary angiography (CAG) after drug-eluting stent (DES) were divided into two groups: those with and without target lesion revascularization (TLR; >50% reduction in luminal stent diameter or angina symptoms on follow-up CAG)...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28252427/renal-function-markers-for-long-term-cardiovascular-prediction-in-individuals-after-myocardial-revascularization
#14
E Levitskaya
Goal - assessment of the renal dysfunction impact on the probability of cardiovascular complications development in the long-term period after myocardial revascularization. 90 patients with ischemic heart disease (IHD) and myocardial revascularization indications were involved in the study. All the patients underwent coronary angiography (CAG), by determining the method of myocardial revascularization (MR) - coronary artery bypass grafting or coronary artery stenting. Traditional risk factors and renal dysfunction markers (albuminuria in the range of 30-300 mg/L, β2-microglobulinuria) were revealed in all the patients examined...
January 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28250337/androgen-receptor-gene-cag-repeat-polymorphism-and-ovarian-cancer-risk-a-meta-analysis
#15
Yang Deng, Jue Wang, Ling Wang, Yan Du
Ovarian cancer is one of the common gynecological malignancies worldwide. It is usually diagnosed at a later stage, thus missing the best opportunity for treatment. Despite the advancement of ovarian cancer treatment, the prognosis is still poor. Androgen receptor (AR) may play a role in ovarian carcinogenesis. Previous studies regarding the association between AR CAG repeat length and ovarian cancer risk reported inconsistent results. Therefore, we conducted a meta-analysis to evaluate the association between AR CAG repeat length and ovarian cancer risk following the MOOSE guidelines...
February 28, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28248067/evaluation-of-stenosis-severity-of-coronary-calcified-lesions-using-transluminal-attenuation-gradient-clinical-application-of-320-row-volume-ct
#16
Yang Fengfeng, Dong Jie, Wang Wei, Wang Xiuting, Fu Xiaojiao, Kumar C Nanda, Zhang Tong
BACKGROUND: To evaluate the accuracy of transluminal attenuation gradient (TAG) in diagnosing the stenosis degree of lesions of difficult to accurately assess the degree of luminal stenosis using coronary computed tomography angiography (CCTA). METHODS: A total of 130 patients consecutively received CCTA and coronary angiography (CAG). The average transluminal Hounsfield units (HU) of the regions of interest were consecutively measured at an interval of 5 mm from the ostium to the distal level, followed by the calculation of TAG...
March 1, 2017: Minerva Medica
https://www.readbyqxmd.com/read/28238795/reversal-of-phenotypic-abnormalities-by-crispr-cas9-mediated-gene-correction-in-huntington-disease-patient-derived-induced-pluripotent-stem%C3%A2-cells
#17
Xiaohong Xu, Yilin Tay, Bernice Sim, Su-In Yoon, Yihui Huang, Jolene Ooi, Kagistia Hana Utami, Amin Ziaei, Bryan Ng, Carola Radulescu, Donovan Low, Alvin Yu Jin Ng, Marie Loh, Byrappa Venkatesh, Florent Ginhoux, George J Augustine, Mahmoud A Pouladi
Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG repeat expansion in HTT. Here we report correction of HD human induced pluripotent stem cells (hiPSCs) using a CRISPR-Cas9 and piggyBac transposon-based approach. We show that both HD and corrected isogenic hiPSCs can be differentiated into excitable, synaptically active forebrain neurons. We further demonstrate that phenotypic abnormalities in HD hiPSC-derived neural cells, including impaired neural rosette formation, increased susceptibility to growth factor withdrawal, and deficits in mitochondrial respiration, are rescued in isogenic controls...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28224887/facile-and-green-fabrication-of-cellulosed-based-aerogels-for-lampblack-filtration-from-waste-newspaper
#18
Peidong Fan, Yali Yuan, Junkai Ren, Bin Yuan, Qian He, Guangmei Xia, Fengxia Chen, Rui Song
In this study, the lightweight, hydrophobic and porous cellulose-based aerogels (CAGs) were synthesized through a freeze-drying process using waste newspaper as the only raw material. After crosslinking with glutaraldehyde and treatment with trimethylchlorosilane (TMCS) using a simple thermal chemical vapor deposition process, the resulting CAGs became hydrophobic and oleophilic. Furthermore, the as-prepared CAGs exhibited a low density (17.4-28.7mgcm(-3)) and mesoporous inner-structure. All these properties attributed the novel aerogel not only with a good adsorption capability of oils and organic solvents, including kerosene, nitrobenzene, and chloroform, but also an excellent filtration capacity of lampblack...
April 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28223462/fallacy-of-the-unique-genome-sequence-diversity-within-single-helicobacter-pylori-strains
#19
Jenny L Draper, Lori M Hansen, David L Bernick, Samar Abedrabbo, Jason G Underwood, Nguyet Kong, Bihua C Huang, Allison M Weis, Bart C Weimer, Arnoud H M van Vliet, Nader Pourmand, Jay V Solnick, Kevin Karplus, Karen M Ottemann
Many bacterial genomes are highly variable but nonetheless are typically published as a single assembled genome. Experiments tracking bacterial genome evolution have not looked at the variation present at a given point in time. Here, we analyzed the mouse-passaged Helicobacter pylori strain SS1 and its parent PMSS1 to assess intra- and intergenomic variability. Using high sequence coverage depth and experimental validation, we detected extensive genome plasticity within these H. pylori isolates, including movement of the transposable element IS607, large and small inversions, multiple single nucleotide polymorphisms, and variation in cagA copy number...
February 21, 2017: MBio
https://www.readbyqxmd.com/read/28223212/n-butilydenephthalide-exhibits-protection-against-neurotoxicity-through-regulation-of-tryptophan-2-3-dioxygenase-in-spinocerebellar-ataxia-type-3
#20
Karthyayani Rajamani, Jen-Wei Liu, Cheng-Han Wu, I-Tsang Chiang, Deng-Huwei You, Si-Yin Lin, Dean-Kuo Hsieh, Shinn-Zong Lin, Horng-Jyh Harn, Tzyy-Wen Chiou
Spinocerebellar ataxia type 3 or Machado-Joseph disease (SCA3/MJD) is characterized by the repetition of a CAG codon in the ataxin-3 gene (ATXN3), which leads to the formation of an elongated mutant ATXN3 protein that can neither be denatured nor undergo proteolysis in the normal manner. This abnormal proteolysis leads to the accumulation of cleaved fragments, which have been identified as toxic and further they act as a seed for more aggregate formation, thereby increasing toxicity in neuronal cells. To date, there have been few studies or treatment strategies that have focused on controlling toxic fragment formation...
February 20, 2017: Neuropharmacology
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