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https://www.readbyqxmd.com/read/28535186/fxr-gankyrin-axis-is-involved-in-development-of-pediatric-liver-cancer
#1
Leila Valanejad, Kyle Lewis, Mary Wright, Yanjun Jiang, Amber D'Souza, Rebekah Karns, Rachel Sheridan, Anita Gupta, Kevin Bove, David Witte, James Geller, Gregory Tiao, David L Nelson, Lubov Timchenko, Nikolai Timchenko
The development of hepatoblastoma (HBL) is associated with failure of hepatic stem cells (HSC) to differentiate into hepatocytes. Despite intensive investigations, mechanisms of the failure of HSC to differentiate are not known. We found that oncogene Gankyrin (Gank) is involved in the inhibition of differentiation of HSC via triggering degradation of tumor suppressor proteins (TSPs) Rb, p53, C/EBPα and HNF4α. Our data show that the activation of a repressor of Gank, farnesoid X receptor, FXR, after initiation of liver cancer by Diethylnitrosamine (DEN) prevents the development of liver cancer by inhibiting Gank and rescuing tumor suppressor proteins...
May 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28533743/neonatal-hypoxia-ischaemia-mechanisms-models-and-therapeutic-challenges
#2
REVIEW
Lancelot J Millar, Lei Shi, Anna Hoerder-Suabedissen, Zoltán Molnár
Neonatal hypoxia-ischaemia (HI) is the most common cause of death and disability in human neonates, and is often associated with persistent motor, sensory, and cognitive impairment. Improved intensive care technology has increased survival without preventing neurological disorder, increasing morbidity throughout the adult population. Early preventative or neuroprotective interventions have the potential to rescue brain development in neonates, yet only one therapeutic intervention is currently licensed for use in developed countries...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28533543/time-dependent-haemoperfusion-after-acute-paraquat-poisoning
#3
Hao-Ru Wang, Jian Pan, An-Dong Shang, Yuan-Qiang Lu
Early haemoperfusion (HP) therapy has been found to be very effective in acute paraquat (PQ) poisoning, but the effective rescue window is still uncertain. Demographic data and the type of therapies administered of 621 patients were included as confounding factors in this retrospective study. After receiver operating characteristic curve analysis and intra-group/subgroup analysis, the initiation of glucocorticoid therapy within 3 hrs of exposure with a second treatment given <21 hrs after exposure, HP initiated within 4 hrs of exposure with a second treatment given <20 hrs after exposure, the appearance of pulmonary lesions ≤8 days after exposure and six other variables were used in a multiple analysis...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533418/hdac1-links-early-life-stress-to-schizophrenia-like-phenotypes
#4
Sanaz Bahari-Javan, Hristo Varbanov, Rashi Halder, Eva Benito, Lalit Kaurani, Susanne Burkhardt, Heike Anderson-Schmidt, Ion Anghelescu, Monika Budde, Roman M Stilling, Joan Costa, Juan Medina, Detlef E Dietrich, Christian Figge, Here Folkerts, Katrin Gade, Urs Heilbronner, Manfred Koller, Carsten Konrad, Sara Y Nussbeck, Harald Scherk, Carsten Spitzer, Sebastian Stierl, Judith Stöckel, Andreas Thiel, Martin von Hagen, Jörg Zimmermann, Antje Zitzelsberger, Sybille Schulz, Andrea Schmitt, Ivana Delalle, Peter Falkai, Thomas G Schulze, Alexander Dityatev, Farahnaz Sananbenesi, André Fischer
Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate with a widespread increase of histone-deacetylase 1 (Hdac1) expression that is linked to altered DNA methylation. Hdac1 overexpression in neurons of the medial prefrontal cortex, but not in the dorsal or ventral hippocampus, mimics schizophrenia-like phenotypes induced by ELS...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28529452/estradiol-suppresses-tlr4-triggered-apoptosis-of-decidual-stromal-cells-and-drives-an-anti-inflammatory-th2-shift-by-activating-sgk1
#5
Yiyun Lou, Minhao Hu, Qijing Wang, Mu Yuan, Ning Wang, Fang Le, Lejun Li, Shisi Huang, Liya Wang, Xiangrong Xu, Fan Jin
A pro-inflammatory cytokine profile at the feto-maternal interface may predispose immune maladaptation notably in early miscarriages. We investigated the involvement of estradiol (E2)-activated serum-glucocorticoid regulated kinase 1 (SGK1) in preserving the tolerogenic and pro-survival intrauterine microenvironment beneficial to gestation maintenance. Decidual SGK1 was down-regulated in early miscarriage, consistent with the lower serum E2 concentration seen in pregnancy loss. Lipopolysaccharide (LPS)/Toll-like receptors 4 (TLR4) signaling induced apoptosis and the pro-inflammatory T helper type (TH) 1 response of decidual stromal cells (DSCs) were associated with miscarriage...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28528135/presymptomatically-applied-ampa-receptor-antagonist-prevents-calcium-increase-in-vulnerable-type-of-motor-axon-terminals-of-mice-modeling-amyotrophic-lateral-sclerosis
#6
Roland Patai, Melinda Paizs, Massimo Tortarolo, Caterina Bendotti, Izabella Obál, József I Engelhardt, László Siklós
Increased intracellular calcium (Ca), which might be the consequence of an excess influx through Ca-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, plays a crucial role in degeneration of motor neurons. Previously we demonstrated that the presymptomatic application of AMPA receptor antagonist, talampanel, could reduce Ca elevation in spinal motor neurons of mice carrying the G93A mutation of superoxide dismutase 1 (SOD1), modeling amyotrophic lateral sclerosis (ALS). It remained to be examined whether the remote, functionally semi-autonomous motor axon terminals could be rescued from the Ca overload, or if the terminals, where the degeneration possibly starts, already experience intractable changes at early time points...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28526875/endophilinas-regulate-endosomal-sorting-of-bdnf-trkb-to-mediate-survival-signaling-in-hippocampal-neurons
#7
Katja Burk, John D Murdoch, Siona Freytag, Melanie Koenig, Vinita Bharat, Ronja Markworth, Susanne Burkhardt, Andre Fischer, Camin Dean
The sorting of activated receptors into distinct endosomal compartments is essential to activate specific signaling cascades and cellular events including growth and survival. However, the proteins involved in this sorting are not well understood. We discovered a novel role of EndophilinAs in sorting of activated BDNF-TrkB receptors into late endosomal compartments. Mice lacking all three EndophilinAs accumulate Rab7-positive late endosomes. Moreover, EndophilinAs are differentially localized to, co-traffic with, and tubulate, distinct endosomal compartments: In response to BDNF, EndophilinA2 is recruited to both early and late endosomes, EndophilinA3 is recruited to Lamp1-positive late endosomes, and co-trafficks with Rab5 and Rab7 in both the presence and absence of BDNF, while EndophilinA1 colocalizes at lower levels with endosomes...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526851/characterization-of-trpa-channels-in-the-starfish-patiria-pectinifera-involvement-of-thermally-activated-trpa1-in-thermotaxis-in-marine-planktonic-larvae
#8
Shigeru Saito, Gen Hamanaka, Narudo Kawai, Ryohei Furukawa, Jun Gojobori, Makoto Tominaga, Hiroyuki Kaneko, Yoko Satta
The vast majority of marine invertebrates spend their larval period as pelagic plankton and are exposed to various environmental cues. Here we investigated the thermotaxis behaviors of the bipinnaria larvae of the starfish, Patiria pectinifera, in association with TRPA ion channels that serve as thermal receptors in various animal species. Using a newly developed thermotaxis assay system, we observed that P. pectinifera larvae displayed positive thermotaxis toward high temperatures, including toward temperatures high enough to cause death...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526479/foxo-mediates-the-timing-of-pupation-through-regulating-ecdysteroid-biosynthesis-in-the-red-flour-beetle-tribolium-castaneum
#9
Xianyu Lin, Na Yu, Guy Smagghe
The steroid hormone 20-hydroxyecdysone (20E), the major developmental hormone in insects, controls all the developmental transitions including ecdysis and metamorphosis. In our study with last larval stages of the red flour beetle, Tribolium castaneum, dsRNA-mediated gene silencing of Forkhead box protein O (FoxO) resulted in reduced food intake and larval mass and this agreed with a reduction in the expression of insulin signaling-related genes (insulin-like peptides 2, 3, 4, and chico). Interestingly, we also observed a significant delay in the moment of the pupation and these FoxO-silenced larvae then died at the middle pupal stage...
May 16, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28526246/impaired-mitophagy-facilitates-mitochondrial-damage-in-danon-disease
#10
Sherin I Hashem, Anne N Murphy, Ajit S Divakaruni, Matthew L Klos, Bradley C Nelson, Emily C Gault, Teisha J Rowland, Cynthia N Perry, Yusu Gu, Nancy D Dalton, William H Bradford, Eric J Devaney, Kirk L Peterson, Kenneth L Jones, Matthew R G Taylor, Ju Chen, Neil C Chi, Eric D Adler
RATIONALE: Lysosomal associated membrane protein type-2 (LAMP-2) is a highly conserved, ubiquitous protein that is critical for autophagic flux. Loss of function mutations in the LAMP-2 gene cause Danon disease, a rare X-linked disorder characterized by developmental delay, skeletal muscle weakness, and severe cardiomyopathy. We previously found that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from Danon patients exhibited significant mitochondrial oxidative stress and apoptosis...
May 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28525886/relationship-between-arterial-access-and-outcomes-in-st-elevation-myocardial-infarction-with-a-pharmacoinvasive-versus-primary-percutaneous-coronary-intervention-strategy-insights-from-the-strategic-reperfusion-early-after-myocardial-infarction-stream-study
#11
Jay Shavadia, Robert Welsh, Anthony Gershlick, Yinggan Zheng, Kurt Huber, Sigrun Halvorsen, Phillipe G Steg, Frans Van de Werf, Paul W Armstrong
BACKGROUND: The effectiveness of radial access (RA) in ST-elevation myocardial infarction (STEMI) has been predominantly established in primary percutaneous coronary intervention (pPCI) with limited exploration of this issue in the early postfibrinolytic patient. The purpose of this study was to compare the effectiveness and safety of RA versus femoral (FA) access in STEMI undergoing either a pharmacoinvasive (PI) strategy or pPCI. METHODS AND RESULTS: Within STrategic Reperfusion Early After Myocardial Infarction (STREAM), we evaluated the relationship between arterial access site and primary outcome (30-day composite of death, shock, congestive heart failure, or reinfarction) and major bleeding according to the treatment strategy received...
June 13, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28523327/complicated-diverticulitis-in-a-de-novo-kidney-transplanted-patient
#12
Liliana Ana TuŢă, Mădălina Boşoteanu, Eugen Dumitru, Mariana Deacu
Diverticular disease is frequent amongst the elderly and immunosuppressed patients. It mainly presents as sigmoid diverticulitis, but severe complications, like bleedings, infections and colon perforation may occur, frequently due to immunosuppressive therapy. Moreover, antibiotherapy and hemostatics may not efficiently control evolution in such cases. Early diagnose and adequate treatment of colonic diverticulosis complicated with lower gastrointestinal bleeding and diverticulitis in immunocompromised patients...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28522250/ppargamma-agonists-rescue-increased-phosphorylation-of-fgf14-at-s226-in-the-tg2576-mouse-model-of-alzheimer-s-disease
#13
Wei-Chun J Hsu, Norelle C Wildburger, Sigmund J Haidacher, Miroslav N Nenov, Oluwarotimi Folorunso, Aditya K Singh, Brent C Chesson, Whitney F Franklin, Ibdanelo Cortez, Rovshan G Sadygov, Kelly T Dineley, Jay S Rudra, Giulio Taglialatela, Cheryl F Lichti, Larry Denner, Fernanda Laezza
BACKGROUND: Cognitive impairment in humans with Alzheimer's disease (AD) and in animal models of Aβ-pathology can be ameliorated by treatments with the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ) agonists, such as rosiglitazone (RSG). Previously, we demonstrated that in the Tg2576 animal model of AD, RSG treatment rescued cognitive deficits and reduced aberrant activity of granule neurons in the dentate gyrus (DG), an area critical for memory formation...
May 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28516283/developmental-window-of-sensorineural-deafness-in-biotinidase-deficient-mice
#14
Kathleen June Maheras, Kirit Pindolia, Barry Wolf, Alexander Gow
Biotinidase deficiency is an autosomal recessively inherited disorder that results in the inability to recycle the vitamin, biotin. If untreated, the disorder can result in a range of neurological and cutaneous symptoms, including sensorineural deficits and deafness. To understand early mechanistic abnormalities that may precede more generalized and nonspecific effects of metabolic deficits such as weight loss and acidosis, we have analyzed auditory brainstem responses (ABRs) in biotinidase-deficient knockout (Btd (-/-) ) mice in the periweaning period with or without dietary biotin supplementation...
May 17, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28515456/metabolomic-analysis-shows-differential-hepatic-effects-of-t2-and-t3-in-rats-after-short-term-feeding-with-high-fat-diet
#15
Liliana F Iannucci, Federica Cioffi, Rosalba Senese, Fernando Goglia, Antonia Lanni, Paul M Yen, Rohit A Sinha
Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515154/progerin-sequestration-of-pcna-promotes-replication-fork-collapse-and-mislocalization-of-xpa-in-laminopathy-related-progeroid-syndromes
#16
Benjamin A Hilton, Ji Liu, Brian M Cartwright, Yiyong Liu, Maya Breitman, Youjie Wang, Rowdy Jones, Hui Tang, Antonio Rusinol, Phillip R Musich, Yue Zou
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that is caused by a point mutation in the LMNA gene resulting in production of a truncated farnesylated-prelamin A protein (progerin). We previously reported that XPA mislocalized to the progerin-induced DNA double-strand break (DSB) sites, blocking DSB repair, which led to DSB accumulation, DNA damage responses, and early replication arrest in HGPS. In this study, the XPA mislocalization to DSBs occurred at stalled or collapsed replication forks, concurrent with a significant loss of PCNA at the forks, whereas PCNA efficiently bound to progerin...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28515048/essential-function-of-the-serine-hydroxymethyl-transferase-shmt-gene-during-rapid-syncytial-cell-cycles-in-drosophila
#17
Franziska Winkler, Maria Kriebel, Michaela Clever, Stephanie Gröning, Jörg Großhans
Many metabolic enzymes are evolutionary highly conserved and serve a central function for catabolism and anabolism of cells. The serine hydroxymethyl transferase (SHMT) catalysing the conversion of serine and glycine and vice versa feeds into the tetrahydrofolate mediated C1 metabolism. We identified a Drosophila mutation in SHMT (CG3011) in a screen for blastoderm mutants. Embryos from SHMT mutant germline clones specifically arrest the cell cycle in interphase 13 at the time of the mid blastula transition (MBT) and prior to cellularisation...
May 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28510727/alternative-splicing-in-the-c-terminal-tail-of-cav2-1-is-essential-for-preventing-a-neurological-disease-in-mice
#18
Tomonori Aikawa, Takaki Watanabe, Taisuke Miyazaki, Takayasu Mikuni, Minoru Wakamori, Miyano Sakurai, Hidenori Aizawa, Nobutaka Ishizu, Masahiko Watanabe, Masanobu Kano, Hidehiro Mizusawa, Kei Watase
Alternative splicing (AS) that occurs at the final coding exon (exon 47) of the Cav2.1 voltage-gated calcium channel (VGCC) gene produces two major isoforms in the brain, MPI and MPc. These isoforms differ in their splice acceptor sites; human MPI is translated into a polyglutamine tract associated with spinocerebellar ataxia type 6 (SCA6), whereas MPc splices to an immediate stop codon, resulting in a shorter cytoplasmic tail.To gain insight into the functional role of the AS in vivo and whether modulating the splice patterns at this locus can be a potential therapeutic strategy for SCA6, here we created knockin mice that exclusively express MPc by inserting the splice-site mutation...
May 16, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28507136/ocd-candidate-gene-slc1a1-eaat3-impacts-basal-ganglia-mediated-activity-and-stereotypic-behavior
#19
Isaac D Zike, Muhammad O Chohan, Jared M Kopelman, Emily N Krasnow, Daniel Flicker, Katherine M Nautiyal, Michael Bubser, Christoph Kellendonk, Carrie K Jones, Gregg Stanwood, Kenji Fransis Tanaka, Holly Moore, Susanne E Ahmari, Jeremy Veenstra-VanderWeele
Obsessive-compulsive disorder (OCD) is a chronic, disabling condition with inadequate treatment options that leave most patients with substantial residual symptoms. Structural, neurochemical, and behavioral findings point to a significant role for basal ganglia circuits and for the glutamate system in OCD. Genetic linkage and association studies in OCD point to SLC1A1, which encodes the neuronal glutamate/aspartate/cysteine transporter excitatory amino acid transporter 3 (EAAT3)/excitatory amino acid transporter 1 (EAAC1)...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28504655/transcription-factors-sohlh1-and-sohlh2-coordinate-oocyte-differentiation-without-affecting-meiosis-i
#20
Yong-Hyun Shin, Yu Ren, Hitomi Suzuki, Kayla J Golnoski, Hyo Won Ahn, Vasil Mico, Aleksandar Rajkovic
Following migration of primordial germ cells to the genital ridge, oogonia undergo several rounds of mitotic division and enter meiosis at approximately E13.5. Most oocytes arrest in the dictyate (diplotene) stage of meiosis circa E18.5. The genes necessary to drive oocyte differentiation in parallel with meiosis are unknown. Here, we have investigated whether expression of spermatogenesis and oogenesis bHLH transcription factor 1 (Sohlh1) and Sohlh2 coordinates oocyte differentiation within the embryonic ovary...
May 15, 2017: Journal of Clinical Investigation
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