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https://www.readbyqxmd.com/read/28230352/disease-modifying-effects-of-m1-muscarinic-acetylcholine-receptor-activation-in-an-alzheimer-s-disease-mouse-model
#1
Evan P Lebois, Jason P Schroeder, Thomas J Esparza, Thomas M Bridges, Craig W Lindsley, P Jeffrey Conn, David L Brody, John Scott Daniels, Allan I Levey
Alzheimer's Disease (AD) is the leading cause of dementia worldwide and currently no disease-modifying therapy is available to slow or prevent AD, underscoring the urgent need for neuroprotective therapies. Selective M1 muscarinic acetylcholine receptor (mAChR) activation is an attractive mechanism for AD therapy since M1 mediates key effects on memory, cognition, and behavior and has potential for disease-modifying effects on Aβ formation and tau phosphorylation. To validate M1 as a neuroprotective treatment target for AD, the M1-selective agonist, VU0364572, was chronically dosed to 5XFAD mice from a young age preceding Aβ pathology (2 months) to an age where these mice are known to display memory impairments (6 months)...
February 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28230093/pentabromophenol-suppresses-tgf-%C3%AE-signaling-by-accelerating-degradation-of-type-ii-tgf-%C3%AE-receptors-via-caveolae-mediated-endocytosis
#2
Chun-Lin Chen, Pei-Hua Yang, Yu-Chen Kao, Pei-Yu Chen, Chih-Ling Chung, Shih-Wei Wang
Pentabromophenol (PBP), a brominated flame retardant (BFR), is widely used in various consumer products. BFRs exert adverse health effects such as neurotoxic and endocrine-disrupting effects. In this study, we found that PBP suppressed TGF-β response by accelerating the turnover rate of TGF-β receptors. PBP suppressed TGF-β-mediated cell migration, PAI-1 promoter-driven reporter gene activation, and Smad2/3 phosphorylation in various cell types. Furthermore, PBP abolished TGF-β-mediated repression of E-cadherin expression, in addition to the induction of vimentin expression and N-cadherin and fibronectin upregulation, thus blocking TGF-β-induced epithelial-mesenchymal transition in A549 and NMuMG cells...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230053/ricin-uses-arginine-235-as-an-anchor-residue-to-bind-to-p-proteins-of-the-ribosomal-stalk
#3
Yijun Zhou, Xiao-Ping Li, Brian Y Chen, Nilgun E Tumer
Ricin toxin A chain (RTA) binds to stalk P-proteins to reach the α-sarcin/ricin loop (SRL) where it cleaves a conserved adenine. Arginine residues at the RTA/RTB interface are involved in this interaction. To investigate the individual contribution of each arginine, we generated single, double and triple arginine mutations in RTA. The R235A mutation reduced toxicity and depurination activity more than any other single arginine mutation in yeast. Further reduction in toxicity, depurination activity and ribosome binding was observed when R235A was combined with a mutation in a nearby arginine...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229934/novel-and-functional-atg12-gene-variants-in-sporadic-parkinson-s-disease
#4
Yuequn Li, Jian Huang, Shuchao Pang, Haihua Wang, Aimei Zhang, Robert G Hawley, Bo Yan
Parkinson's disease (PD) is a common and progressive neurodegenerative disease, including familial and sporadic cases. To date, genetic causes for sporadic PD, majority of PD cases, remain largely unknown. Accumulating evidence indicates that dysfunctional autophagy, a highly conserved cellular process, is involved in the PD pathogenesis. We speculated that changed expression levels of autophagy-related genes (ATG) may contribute to PD development. Previously, we have genetically analyzed ATG5 and ATG7 genes in sporadic PD patients and identified several functional DNA sequence variants (DSVs)...
February 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28229932/csn5-jab1-suppresses-the-wnt-inhibitor-dkk1-in-colorectal-cancer-cells
#5
Sandra Jumpertz, Thomas Hennes, Yaw Asare, Anke K Schütz, Jürgen Bernhagen
The COP9 signalosome (CSN) is a multi-protein complex that is highly conserved in eukaryotes. Due to its regulatory impact on processes such as cell cycle, DNA damage response and apoptosis, the CSN is essential for mammalian cells. One of the best-studied functions of the CSN is the deNEDDylation of cullin-RING ligases (CRLs) via its catalytically active subunit CSN5/JAB1, thereby triggering the degradation of various target proteins. CSN5 was found to be overexpressed in many human cancer entities, including colon adenocarcinoma...
February 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28229263/exosomes-derived-from-human-amniotic-epithelial-cells-accelerate-wound-healing-and-inhibit-scar-formation
#6
Bin Zhao, Yijie Zhang, Shichao Han, Wei Zhang, Qin Zhou, Hao Guan, Jiaqi Liu, Jihong Shi, Linlin Su, Dahai Hu
Wound healing is a highly orchestrated physiological process consisting of a complex events, and scarless wound healing is highly desired for the development and application in clinical medicine. Recently, we have demonstrated that human amniotic epithelial cells (hAECs) promoted wound healing and inhibited scar formation through a paracrine mechanism. However, exosomes (Exo) are one of the most important paracrine factors. Whether exosomes derived from human amniotic epithelial cells (hAECs-Exo) have positive effects on scarless wound healing have not been reported yet...
February 22, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28228725/differential-effects-of-corm-2-and-corm-401-in-murine-intestinal-epithelial-mode-k-cells-under-oxidative-stress
#7
Dinesh Babu, Georges Leclercq, Roberto Motterlini, Romain A Lefebvre
Carbon monoxide (CO)-releasing molecules (CO-RMs) are intensively studied to provide cytoprotective and anti-inflammatory effects of CO in inflammatory conditions including intestinal inflammation. The water-soluble CORM-A1 reduced apoptosis and NADPH oxidase (NOX)-derived reactive oxygen species (ROS) induced by tumor necrosis factor (TNF)-α/cycloheximide (CHX) in mouse MODE-K intestinal epithelial cells (IECs), without influencing TNF-α/CHX-induced mitochondrial superoxide anion ([Formula: see text]). The aim of the present study in the same model was to comparatively investigate the influence of lipid-soluble CORM-2 and water-soluble CORM-401, shown in vitro to release more CO under oxidative conditions...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28228474/changes-in-ambient-temperature-elicit-divergent-control-of-metabolic-and-cardiovascular-actions-by-leptin
#8
Jussara M do Carmo, Alexandre A da Silva, Damian G Romero, John E Hall
Interactions of hypothalamic signaling pathways that control body temperature (BT), blood pressure (BP), and energy balance are poorly understood. We investigated whether the chronic BP and metabolic actions of leptin are differentially modulated by changes in ambient temperature (TA ). Mean arterial pressure (MAP), heart rate (HR), BT, motor activity (MA), and oxygen consumption (Vo2) were measured 24 h/d at normal laboratory TA (23°C), at thermoneutral zone (TNZ, 30°C) for mice or during cold exposure (15°C) in male wild-type mice...
February 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28228439/loss-of-pollen-specific-phospholipase-not-like-dad-triggers-gynogenesis-in-maize
#9
Laurine M Gilles, Abdelsabour Khaled, Jean-Baptiste Laffaire, Sandrine Chaignon, Ghislaine Gendrot, Jérôme Laplaige, Hélène Bergès, Genséric Beydon, Vincent Bayle, Pierre Barret, Jordi Comadran, Jean-Pierre Martinant, Peter M Rogowsky, Thomas Widiez
Gynogenesis is an asexual mode of reproduction common to animals and plants, in which stimuli from the sperm cell trigger the development of the unfertilized egg cell into a haploid embryo. Fine mapping restricted a major maize QTL (quantitative trait locus) responsible for the aptitude of inducer lines to trigger gynogenesis to a zone containing a single gene NOT LIKE DAD (NLD) coding for a patatin-like phospholipase A. In all surveyed inducer lines, NLD carries a 4-bp insertion leading to a predicted truncated protein...
February 22, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28228403/antenatal-betamethasone-attenuates-the-angiotensin-1-7-mas-receptor-nitric-oxide-axis-in-isolated-proximal-tubule-cells
#10
Yixin Su, Jianli Bi, Victor M Pulgar, Mark C Chappell, James C Rose
We previously reported a sex-specific effect of antenatal treatment with betamethasone (Beta) on sodium (Na(+)) excretion in adult sheep whereby treated males but not females had an attenuated natriuretic response to Ang-(1-7). The present study determined the Na(+) uptake and nitric oxide (NO) response to low dose Ang-(1-7) (1 pM) in renal proximal tubule cells (RPTC) from adult male and female sheep antenatally exposed to Beta or vehicle. Data were expressed as % of basal uptake or area under the curve (AUC) for Na(+) or % of control for NO...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28228259/sirt1-regulates-dna-methylation-and-differentiation-potential-of-embryonic-stem-cells-by-antagonizing-dnmt3l
#11
Jinbeom Heo, Jisun Lim, Seungun Lee, Jaeho Jeong, Hyunsook Kang, YongHwan Kim, Jeong Wook Kang, Hwan Yeul Yu, Eui Man Jeong, Kyunggon Kim, Magda Kucia, Sabine J Waigel, Wolfgang Zacharias, Yinlu Chen, In-Gyu Kim, Mariusz Z Ratajczak, Dong-Myung Shin
Embryonic stem cell (ESC) abnormalities in genome methylation hamper the utility of their therapeutic derivatives; however, the underlying mechanisms are unknown. Here, we show that the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, Sirt1, selectively prevents abnormal DNA methylation of some developmental genes in murine ESCs by antagonizing Dnmt3l. Transcriptome and DNA methylome analyses demonstrated that Sirt1-null (Sirt1(-/-)) ESCs repress expression of a subset of imprinted and germline genes concomitant with increased DNA methylation of regulatory elements...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28226462/effects-and-underlying-mechanisms-of-refractory-period-pacing-on-repolarization-dynamics-in-the-human-heart
#12
Diogo Santos, Michele Orini, Xin Zhou, Alfonso Bueno-Orovio, Ben Hanson, Peter Taggart, Martin Hayward, Blanca Rodriguez, Pier Lambiase, Diogo Santos, Michele Orini, Xin Zhou, Alfonso Bueno-Orovio, Ben Hanson, Peter Taggart, Martin Hayward, Blanca Rodriguez, Pier Lambiase, Ben Hanson, Diogo Santos, Martin Hayward, Pier Lambiase, Alfonso Bueno-Orovio, Blanca Rodriguez, Michele Orini, Xin Zhou, Peter Taggart
Repolarization alternans is related to the initiation of life threatening cardiac arrhythmias. Experimental and computational studies suggest that the abolishment of alternans using dynamic pacing protocols may prevent abnormal heart rhythms. In a recent animal study, refractory period pacing (RPP) on every other beat has shown promising results in alternans reduction. However, the cellular mechanisms underlying this therapy and its efficiency in human patients remain unclear. In this study, in vivo unipolar electrograms acquired during RPP from 240 epicardial sites from one patient were analysed...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226198/olanzapine-induced-early-cardiovascular-effects-are-mediated-by-the-biological-clock-and-prevented-by-melatonin
#13
Francisco Romo-Nava, Frederik N Buijs, Marcela Valdés-Tovar, Gloria Benítez-King, MariCarmen Basualdo, Mercedes Perusquía, Gerhard Heinze, Carolina Escobar, Ruud M Buijs
Second generation antipsychotics (SGA) are associated with adverse cardiometabolic side-effects contributing to premature mortality in patients. While mechanisms mediating these cardiometabolic side-effects remain poorly understood, three independent studies recently demonstrated that melatonin was protective against cardiometabolic risk in SGA-treated patients. Since one of the main target areas of circulating melatonin in the brain is the suprachiasmatic nucleus (SCN), we hypothesized that the SCN is involved in SGA-induced early cardiovascular effects in Wistar rats...
February 22, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28225068/relish2-mediates-bursicon-homodimer-induced-prophylactic-immunity-in-the-mosquito-aedes-aegypti
#14
Hongwei Zhang, Shengzhang Dong, Xi Chen, David Stanley, Brenda Beerntsen, Qili Feng, Qisheng Song
Bursicon is a neuropeptide hormone consisting of two cystine-knot proteins (burs α and burs β), responsible for cuticle tanning and other developmental processes in insects. Recent studies show that each bursicon subunit forms homodimers that induce prophylactic immunity in Drosophila melanogaster. Here, we investigated the hypothesis that bursicon homodimers act in prophylactic immunity in insects, and possibly arthropods, generally, using the mosquito, Aedes aegypti. We found that burs α and burs β are expressed in larvae, pupae and newly emerged adults...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223469/maternal-gestational-hypertension-induced-sensitization-of-angiotensin-ii-hypertension-is-reversed-by-renal-denervation-or-angiotensin-converting-enzyme-inhibition-in-rat-offspring
#15
Baojian Xue, Haifeng Yin, Fang Guo, Terry G Beltz, Robert L Thunhorst, Alan Kim Johnson
Numerous findings demonstrate that there is a strong association between maternal health during pregnancy and cardiovascular disease in adult offspring. The purpose of the present study was to test whether maternal gestational hypertension modulates brain renin-angiotensin-aldosterone system (RAAS) and proinflammatory cytokines that sensitizes angiotensin II-elicited hypertensive response in adult offspring. In addition, the role of renal nerves and the RAAS in the sensitization process was investigated. Reverse transcription polymerase chain reaction analyses of structures of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAAS components and proinflammatory cytokines in 10-week-old male offspring of hypertensive dams...
February 21, 2017: Hypertension
https://www.readbyqxmd.com/read/28223425/role-of-stat3-and-foxo1-in-the-divergent-therapeutic-responses-of-non-metastatic-and-metastatic-bladder-cancer-cells-to-mir-145
#16
Guosong Jiang, Chao Huang, Jingxia Li, Haishan Huang, Honglei Jin, Junlan Zhu, Xue-Ru Wu, Chuanshu Huang
Although miR-145 is the most frequently down-regulated miRNA in bladder cancer (BC), its exact stage-association and downstream effector have not been defined. Here, we found that miR-145 was upregulated in human BC patients with lymph node metastasis and in metastatic T24T cell line. Forced expression of miR-145 promoted anchorage-independent growth of T24T cells accompanied by the down-regulation of forkhead box class O1 (FOXO1). In contrast, in non-metastatic T24 cells, miR-145 overexpression inhibited cell growth with upregulation of FOXO1 and the knockdown of FOXO1 abolished the miR-145-mediated inhibition of cell growth...
February 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28223362/mechanistic-insights-into-the-allosteric-regulation-of-bacterial-adp-glucose-pyrophosphorylases
#17
Natalia Comino, Javier Cifuente, Alberto Marina, Ane Orrantia, Ander Eguskiza, Marcelo E Guerin
ADP-glucose pyrophosphorylase (AGPase) controls bacterial glycogen and plant starch biosynthetic pathways, the most common carbon storage polysaccharides in nature. AGPase activity is allosterically regulated by a series of metabolites in the energetic flux within the cell. Very recently, we reported the first crystal structures of the paradigmatic AGPase from Escherichia coli (EcAGPase) in complex with its preferred physiological negative and positive allosteric regulators, adenosine-5'-monophosphate (AMP) and fructose-1,6-bisphosphate (FBP), respectively...
February 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28223356/molecular-insights-into-hydrogen-peroxide-sensing-mechanism-of-the-metalloregulator-mntr-in-controlling-bacterial-resistance-to-oxidative-stresses
#18
Zhaoyuan Chen, Xinhui Wang, Fan Yang, Qingqing Hu, Huichun Tong, Xiuzhu Dong
Manganese contributes to anti-oxidative stress particularly in catalase-devoid bacteria, and DtxR family metalloregulators, through sensing cellular Mn(2+) content, regulate its homeostasis. Here, we show that metalloregulator MntR (So-MntR) functions dually as Mn(2+) and H2O2 sensors in mediating H2O2 resistance by an oral streptococcus. H2O2 disrupted So-MntR's binding to Mn(2+) transporter mntABC promoter, and induced disulfide-linked dimerization of the protein. Mass spectrometry identified Cys11-Cys156 and Cys11-Cys11 disulfide-linked peptides in H2O2 treated So-MntR...
February 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28223311/single-tumor-initiating-cells-evade-immune-clearance-by-recruiting-type-ii-macrophages
#19
Xiaocan Guo, Yang Zhao, Huan Yan, Yingcheng Yang, Shuying Shen, Xiaoming Dai, Xinyan Ji, Fubo Ji, Xing-Guo Gong, Li Li, Xueli Bai, Xin-Hua Feng, Tingbo Liang, Junfang Ji, Lei Chen, Hongyang Wang, Bin Zhao
Tumor infiltrated type II (M2) macrophages promote tumorigenesis by suppressing immune clearance, promoting proliferation, and stimulating angiogenesis. Interestingly, macrophages were also found to enrich in small foci of altered hepatocytes containing liver tumor-initiating cells (TICs). However, whether and how TICs specifically recruit macrophages and the function of these macrophages in tumor initiation remain unknown due to technical difficulties. In this study, by generating genetically defined liver TICs, we demonstrate that TICs actively recruit M2 macrophages from as early as the single-cell stage...
February 21, 2017: Genes & Development
https://www.readbyqxmd.com/read/28223240/carbachol-induced-network-oscillations-in-an-in-vitro-limbic-system-brain-slice
#20
Maxime Lévesque, Mauro Cataldi, Li-Yuan Chen, Shabnam Hamidi, Massimo Avoli
We employed simultaneous field potential recordings from CA3, subiculum and entorhinal cortex in an in vitro brain slice preparation to understand the involvement of these limbic areas in the generation of the field potential oscillations that are induced by bath application of the muscarinic receptor agonist carbachol. Regularly spaced oscillations that mainly presented at theta frequency range (5-12 Hz) occurred synchronously in all three structures in the presence of carbachol. These oscillations, which disappeared when slices were perfused with pirenzepine or with glutamatergic receptor antagonists, were categorized as short (< 4 s) and long (> 4s) with short events oscillating at higher frequencies than long events...
February 18, 2017: Neuroscience
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