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https://www.readbyqxmd.com/read/28806855/functional-stem-cell-integration-into-neural-networks-assessed-by-organotypic-slice-cultures
#1
David Forsberg, Charoensri Thonabulsombat, Johan Jäderstad, Linda Maria Jäderstad, Petri Olivius, Eric Herlenius
Re-formation or preservation of functional, electrically active neural networks has been proffered as one of the goals of stem cell-mediated neural therapeutics. A primary issue for a cell therapy approach is the formation of functional contacts between the implanted cells and the host tissue. Therefore, it is of fundamental interest to establish protocols that allow us to delineate a detailed time course of grafted stem cell survival, migration, differentiation, integration, and functional interaction with the host...
August 14, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28806778/serum-resistin-as-an-independent-marker-of-aortic-stiffness-in-patients-with-coronary-artery-disease
#2
Ji-Hung Wang, Chung-Jen Lee, Chiu-Fen Yang, Yu-Chih Chen, Bang-Gee Hsu
BACKGROUND: Subjects with higher carotid-femoral pulse wave velocity (cfPWV) will be at an increased risk for cardiovascular (CV) events in future. Resistin is an inflammatory mediator and a biomarker of CV diseases. We evaluated the association between serum resistin and aortic stiffness in patients with coronary artery disease (CAD). METHODS: A total of 104 patients with CAD were enrolled in this study. cfPWV was measured using the SphygmoCor system. Patients with cfPWV >10 m/s were defined as the high aortic stiffness group...
2017: PloS One
https://www.readbyqxmd.com/read/28806774/fibroblast-growth-factor-receptor-1-mediates-internalization-of-pathogenic-spotted-fever-rickettsiae-into-host-endothelium
#3
Abha Sahni, Jignesh Patel, Hema P Narra, Casey L C Schroeder, David H Walker, Sanjeev K Sahni
Rickettsial infections continue to cause serious morbidity and mortality in severe human cases around the world. Host cell adhesion and invasion is an essential requisite for intracellular growth, replication, and subsequent dissemination of pathogenic rickettsiae. Heparan sulfate proteoglycans [HSPGs] facilitate the interactions between fibroblast growth factor(s) and their tyrosine kinase receptors resulting in receptor dimerization/activation and have been implicated in bacterial adhesion to target host cells...
2017: PloS One
https://www.readbyqxmd.com/read/28806762/a-becn1-mutation-mediates-hyperactive-autophagic-sequestration-of-amyloid-oligomers-and-improved-cognition-in-alzheimer-s-disease
#4
Altea Rocchi, Soh Yamamoto, Tabitha Ting, Yuying Fan, Katherine Sadleir, Yigang Wang, Weiran Zhang, Sui Huang, Beth Levine, Robert Vassar, Congcong He
Impairment of the autophagy pathway has been observed during the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder characterized by abnormal deposition of extracellular and intracellular amyloid β (Aβ) peptides. Yet the role of autophagy in Aβ production and AD progression is complex. To study whether increased basal autophagy plays a beneficial role in Aβ clearance and cognitive improvement, we developed a novel genetic model to hyperactivate autophagy in vivo. We found that knock-in of a point mutation F121A in the essential autophagy gene Beclin 1/Becn1 in mice significantly reduces the interaction of BECN1 with its inhibitor BCL2, and thus leads to constitutively active autophagy even under non-autophagy-inducing conditions in multiple tissues, including brain...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28806745/persistent-mycobacteria-evade-an-antibacterial-program-mediated-by-phagolysosomal-tlr7-8-myd88-in-human-primary-macrophages
#5
Alexandre Gidon, Signe Elisabeth Åsberg, Claire Louet, Liv Ryan, Markus Haug, Trude Helen Flo
Pathogenic mycobacteria reside in macrophages where they avoid lysosomal targeting and degradation through poorly understood mechanisms proposed to involve arrest of phagosomal maturation at an early endosomal stage. A clear understanding of how this relates to host defenses elicited from various intracellular compartments is also missing and can only be studied using techniques allowing single cell and subcellular analyses. Using confocal imaging of human primary macrophages infected with Mycobacterium avium (Mav) we show evidence that Mav phagosomes are not arrested at an early endosomal stage, but mature to a (LAMP1+/LAMP2+/CD63+) late endosomal/phagolysosomal stage where inflammatory signaling and Mav growth restriction is initiated through a mechanism involving Toll-like receptors (TLR) 7 and 8, the adaptor MyD88 and transcription factors NF-κB and IRF-1...
August 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28806727/formation-of-friable-embryogenic-callus-in-cassava-is-enhanced-under-conditions-of-reduced-nitrate-potassium-and-phosphate
#6
Yoshinori Utsumi, Chikako Utsumi, Maho Tanaka, Vu The Ha, Akihiro Matsui, Satoshi Takahashi, Motoaki Seki
Agrobacterium-mediated transformation is an important research tool for the genetic improvement of cassava. The induction of friable embryogenic callus (FEC) is considered as a key step in cassava transformation. In the present study, the media composition was optimized for enhancing the FEC induction, and the effect of the optimized medium on gene expression was evaluated. In relative comparison to MS medium, results demonstrated that using a medium with reducing nutrition (a 10-fold less concentration of nitrogen, potassium, and phosphate), the increased amount of vitamin B1 (10 mg/L) and the use of picrolam led to reprogram non-FEC to FEC...
2017: PloS One
https://www.readbyqxmd.com/read/28806703/nox4-mediated-ros-production-induces-apoptotic-cell-death-via-down-regulation-of-c-flip-and-mcl-1-expression-in-combined-treatment-with-thioridazine-and-curcumin
#7
Seung Un Seo, Tae Hwan Kim, Dong Eun Kim, Kyoung-Jin Min, Taeg Kyu Kwon
Thioridazine is known to have anti-tumor effects by inhibiting PI3K/Akt signaling, which is an important signaling pathway in cell survival. However, thioridazine alone does not induce apoptosis in head and neck squamous cell carcinoma (AMC-HN4), human breast carcinoma (MDA-MB231), and human glioma (U87MG) cells. Therefore, we investigated whether combined treatment with thioridazine and curcumin induces apoptosis. Combined treatment with thioridazine and curcumin markedly induced apoptosis in cancer cells without inducing apoptosis in human normal mesangial cells and human normal umbilical vein cells (EA...
August 9, 2017: Redox Biology
https://www.readbyqxmd.com/read/28806702/hmgb1-redox-during-sepsis
#8
Wasan Abdulmahdi, Devika Patel, May M Rabadi, Tala Azar, Edson Jules, Mark Lipphardt, Rameen Hashemiyoon, Brian B Ratliff
During sepsis, the alarmin HMGB1 is released from tissues and promotes systemic inflammation that results in multi-organ damage, with the kidney particularly susceptible to injury. The severity of inflammation and pro-damage signaling mediated by HMGB1 appears to be dependent on the alarmin's redox state. Therefore, we examined HMGB1 redox in kidney cells during sepsis. Using intravital microscopy, CellROX labeling of kidneys in live mice indicated increased ROS generation in the kidney perivascular endothelium and tubules during lipopolysaccharide (LPS)-induced sepsis...
August 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28806639/a-developmental-etiological-model-for-drug-abuse-in-men
#9
Kenneth S Kendler, Henrik Ohlsson, Alexis C Edwards, Jan Sundquist, Kristina Sundquist
BACKGROUND: We attempt to develop a relatively comprehensive structural model of risk factors for drug abuse (DA) in Swedish men that illustrates developmental and mediational processes. METHODS: We examined 20 risk factors for DA in 48,369 men undergoing conscription examinations in 1969-70 followed until 2011 when 2.34% (n=1134) of them had DA ascertained in medical, criminal and pharmacy registries. Risk factors were organized into four developmental tiers reflecting i) birth, ii) childhood/early adolescence, iii) late adolescence, and iv) young adulthood...
July 29, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28806587/elucidation-of-host-pathogen-protein-protein-interactions-to-uncover-mechanisms-of-host-cell-rewiring
#10
REVIEW
Charlotte Nicod, Amir Banaei-Esfahani, Ben C Collins
Infectious diseases are the result of molecular cross-talks between hosts and their pathogens. These cross-talks are in part mediated by host-pathogen protein-protein interactions (HP-PPI). HP-PPI play crucial roles in infections, as they may tilt the balance either in favor of the pathogens' spread or their clearance. The identification of host proteins targeted by viral or bacterial pathogenic proteins necessary for the infection can provide insights into their underlying molecular mechanisms of pathogenicity, and potentially even single out pharmacological intervention targets...
August 11, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28806532/the-impact-of-an-acute-oral-phosphate-load-on-endothelium-dependent-and-independent-brachial-artery-vasodilation-in-healthy-males
#11
Brendan M Levac, Michael A Adams, Kyra E Pyke
Serum phosphate levels are associated with cardiovascular morbidity and mortality in the general population and endothelial dysfunction may be mechanistically involved. The purpose of this study was to investigate the effects of acute phosphate supplementation on endothelial-dependent (Flow mediated dilation (FMD)) and -independent (Glyceryl trinitrate (GTN)) vasodilation in young, healthy males. 17 healthy male participants (23±3 years old) were exposed to an oral load of phosphate (PHOS; (liquid supplement containing 1200 mg of phosphorous) and placebo (PLAC) over two experimental days...
August 14, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28806519/pluronic-p85-f68-micelles-of-baicalein-could-interfere-with-mitochondria-to-overcome-mrp2-mediated-efflux-and-offer-improved-anti-parkinsonian-activity
#12
Tongkai Chen, Ye Li, Chuwen Li, Xiang Yi, Ruibing Wang, Simon Ming Yuen Lee, Ying Zheng
Overexpression of the drug efflux transporter multidrug resistance-associated protein 2 (MRP2) in the gastrointestinal tract and blood-brain barrier compromises the oral delivery of drugs to the circulation system and brain in the treatment of Parkinson's disease (PD). In this study, we aim to develop small-sized Pluronic P85/F68 micelles loaded with baicalein (B-MCs) to overcome MRP2-mediated efflux and to investigate related mechanism, as well as the anti-Parkinsonian efficacy. Spherical and sustained-release B-MCs have a mean particle size of 40...
August 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28806503/identification-of-the-dimer-exchange-interface-of-the-bacterial-dna-damage-response-protein-umud
#13
David A Murison, Rebecca C Timson, Bilyana Koleva, Michael Ordazzo, Penny J Beuning
The Escherichia coli SOS response, an induced DNA damage response pathway, confers survival on bacterial cells by providing accurate repair mechanisms as well as the potentially mutagenic pathway translesion synthesis (TLS). The umuD gene products are upregulated after DNA damage and play roles in both non-mutagenic and mutagenic aspects of the SOS response. Full-length UmuD is expressed as a homodimer of 139-amino-acid subunits, which eventually cleaves its N-terminal 24 amino acids to form UmuD'. The cleavage product, UmuD', together with UmuC, form the Y-family polymerase DNA Pol V (UmuD'2C) capable of performing TLS...
August 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28806500/doxepin-mitigates-noise-induced-neuronal-damage-in-primary-auditory-cortex-of-mice-via-suppression-of-acid-sphingomyelinase-ceramide-pathway
#14
Yu-Ting Su, Xing-Xing Meng, Xi Zhang, Yi-Bin Guo, Hai-Jun Zhang, Yao-Ping Cheng, Xiao-Ping Xie, Yao-Ming Chang, Jun-Xiang Bao
Neuronal damage in primary auditory cortex (A1) underlies complex manifestations of noise exposure, prevention of which is critical for health maintenance. Acid sphingomyelinase (ASM) catalyzes generation of ceramide (Cer) which if over-activated mediates neuronal disorders in various diseases. Tricyclic antidepressants (TCAs), by restraining ASM/Cer, benefits multiple neuronal anomalies, so we aimed to elucidate the effect of TCA on noise induced hearing loss and auditory cortex derangement, unraveling mechanism involved...
August 14, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28806486/farmworker-vulnerability-to-heat-hazards-a-conceptual-framework
#15
Valerie Vi Thien Mac, Linda A McCauley
PURPOSE: To review factors that impact the effect of hot environments on the human body in order to develop a conceptual model of human biological response. METHODS: The organizing concept for the model development was the multilevel integration of three major factors, exposure to heat, sensitivity and adaptive capacity, and the heat stress response. Exposure of a vulnerable occupational group was used to illustrate the components of the model. FINDINGS: Components of this framework include the hazard (environmental heat stress), vulnerability factors (workplace exposure, sensitivity and adaptive capacity), and the heat stress response...
August 14, 2017: Journal of Nursing Scholarship
https://www.readbyqxmd.com/read/28806404/rig-i-and-il-6-are-negative-feedback-regulators-of-sting-induced-by-double-stranded-dna
#16
Xueling Wu, Jun Yang, Tao Na, Kehua Zhang, Andrew M Davidoff, Bao-Zhu Yuan, Youchun Wang
The stimulator of interferon genes (STING) protein has emerged as a critical signal transduction molecule in the innate immune response. Sustained activation of the STING signaling induced by cytosolic DNA has been considered to be the cause of a variety of autoimmune diseases characterized by uncontrolled inflammation. Therefore, it is important to understand the molecular basis of the regulation of STING signaling pathway. Here we demonstrate that the STING protein undergoes a proteasome-mediated degradation in human diploid cell (HDC) lines including MRC-5 following the transfection of double-stranded DNA (dsDNA)...
2017: PloS One
https://www.readbyqxmd.com/read/28806402/multi-functional-mechanisms-of-immune-evasion-by-the-streptococcal-complement-inhibitor-c5a-peptidase
#17
Nicola N Lynskey, Mark Reglinski, Damien Calay, Matthew K Siggins, Justin C Mason, Marina Botto, Shiranee Sriskandan
The complement cascade is crucial for clearance and control of invading pathogens, and as such is a key target for pathogen mediated host modulation. C3 is the central molecule of the complement cascade, and plays a vital role in opsonization of bacteria and recruitment of neutrophils to the site of infection. Streptococcal species have evolved multiple mechanisms to disrupt complement-mediated innate immunity, among which ScpA (C5a peptidase), a C5a inactivating enzyme, is widely conserved. Here we demonstrate for the first time that pyogenic streptococcal species are capable of cleaving C3, and identify C3 and C3a as novel substrates for the streptococcal ScpA, which are functionally inactivated as a result of cleavage 7 amino acids upstream of the natural C3 convertase...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28806401/a-gdf15-3-utr-variant-rs1054564-results-in-allele-specific-translational-repression-of-gdf15-by-hsa-mir-1233-3p
#18
Ming-Sheng Teng, Lung-An Hsu, Shu-Hui Juan, Wen-Chi Lin, Ming-Cheng Lee, Cheng-Wen Su, Semon Wu, Yu-Lin Ko
Growth differentiation factor 15 (GDF15) is a strong predictor of cardiovascular events and mortality in individuals with or without cardiovascular diseases. Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) target sites, also known as miRSNPs, are known to enhance or weaken miRNA-mRNA interactions and have been linked to diseases such as cardiovascular disease and cancer. In this study, we aimed to elucidate the functional significance of the miRSNP rs1054564 in regulating GDF15 levels. Two rs1054564-containing binding sites for hsa-miR-873-5p and hsa-miR-1233-3p were identified in the 3' untranslated region (UTR) of the GDF15 transcript using bioinformatics tools...
2017: PloS One
https://www.readbyqxmd.com/read/28806398/lysine-52-stabilizes-the-myc-oncoprotein-through-an-scf-fbxw7-independent-mechanism
#19
J De Melo, S S Kim, C Lourenco, L Z Penn
The oncogenic transcription factor c-MYC (MYC) is deregulated and often overexpressed in more than 50% of cancers. MYC deregulation is associated with poor prognosis and aggressive disease, suggesting that the development of therapeutic inhibitors targeting MYC would markedly impact patient outcome. MYC is highly regulated, with a protein and mRNA half-life of ~30 min. The most extensively studied pathway regulating MYC protein stability involves ubiquitylation and proteasomal degradation mediated by the E3-ligase, SCF(Fbxw7)...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28806395/rad6-promotes-dna-repair-and-stem-cell-signaling-in-ovarian-cancer-and-is-a-promising-therapeutic-target-to-prevent-and-treat-acquired-chemoresistance
#20
R R Somasagara, S M Spencer, K Tripathi, D W Clark, C Mani, L Madeira da Silva, J Scalici, H Kothayer, A D Westwell, R P Rocconi, K Palle
Ovarian cancer (OC) is the most deadly gynecological cancer and unlike most other neoplasms, survival rates for OC have not significantly improved in recent decades. We show that RAD6, an ubiquitin-conjugating enzyme, is significantly overexpressed in ovarian tumors and its expression increases in response to carboplatin chemotherapy. RAD6 expression correlated strongly with acquired chemoresistance and malignant behavior of OC cells, expression of stem cell genes and poor prognosis of OC patients, suggesting an important role for RAD6 in ovarian tumor progression...
August 14, 2017: Oncogene
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