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https://www.readbyqxmd.com/read/29430765/identifying-the-target-genes-of-suppressor-of-gamma-response-1-a-master-transcription-factor-controlling-dna-damage-response-in-arabidopsis
#1
Nobuo Ogita, Yoko Okushima, Mutsutomo Tokizawa, Yoshiharu Y Yamamoto, Maho Tanaka, Motoaki Seki, Yuko Makita, Minami Matsui, Kaoru Okamoto Yoshiyama, Tomoaki Sakamoto, Tetsuya Kurata, Kei Hiruma, Yusuke Saijo, Naoki Takahashi, Masaaki Umeda
In mammalian cells, the transcription factor p53 plays a crucial role in transmitting DNA damage signals to maintain genome integrity. However, in plants, orthologous genes for p53 and checkpoint proteins are absent. Instead, the plant-specific transcription factor SUPPRESSOR OF GAMMA RADIATION 1 (SOG1) controls most of the genes induced by gamma irradiation and promotes DNA repair, cell cycle arrest, and stem cell death. Thus far, the genes directly controlled by SOG1 remain largely unknown, limiting the understanding of DNA damage signaling in plants...
February 11, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29428213/nigrostriatal-proteasome-inhibition-impairs-dopamine-neurotransmission-and-motor-function-in-minipigs
#2
Thea P Lillethorup, Andreas N Glud, Aage K O Alstrup, Trine W Mikkelsen, Erik H Nielsen, Hamed Zaer, Doris J Doudet, David J Brooks, Jens Christian H Sørensen, Dariusz Orlowski, Anne M Landau
Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra leading to slowness and stiffness of limb movement with rest tremor. Using ubiquitin proteasome system inhibitors, rodent models have shown nigrostriatal degeneration and motor impairment. We translated this model to the Göttingen minipig by administering lactacystin into the medial forebrain bundle (MFB). Minipigs underwent positron emission tomography (PET) imaging with (+)-α-[11C]dihydrotetrabenazine ([11C]DTBZ), a marker of vesicular monoamine transporter 2 availability, at baseline and three weeks after the unilateral administration of 100 μg lactacystin into the MFB...
February 8, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29416003/the-antitumor-natural-product-tanshinone-iia-inhibits-protein-kinase-c-and-acts-synergistically-with-17-aag
#3
Chao Lv, Hua-Wu Zeng, Jin-Xin Wang, Xing Yuan, Chuang Zhang, Ting Fang, Pei-Ming Yang, Tong Wu, Yu-Dong Zhou, Dale G Nagle, Wei-Dong Zhang
Tanshinone IIA (Tan IIA), the primary bioactive compound derived from the traditional Chinese medicine (TCM) Salvia miltiorrhiza Bunge, has been reported to possess antitumor activity. However, its antitumor mechanisms are not fully understood. To resolve the potential antitumor mechanism(s) of Tan IIA, its gene expression profiles from our database was analyzed by connectivity map (CMAP) and the CMAP-based mechanistic predictions were confirmed/validated in further studies. Specifically, Tan IIA inhibited total protein kinase C (PKC) activity and selectively suppressed the expression of cytosolic and plasma membrane PKC isoforms ζ and ε...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29391407/dysregulated-fibronectin-trafficking-by-hsp90-inhibition-restricts-prostate-cancer-cell-invasion
#4
Heather K Armstrong, Joanna L Gillis, Ian R D Johnson, Zeyad D Nassar, Max Moldovan, Claire Levrier, Martin C Sadowski, Mei Yieng Chin, Emma S Tomlinson Guns, Gerard Tarulli, David J Lynn, Douglas A Brooks, Luke A Selth, Margaret M Centenera, Lisa M Butler
The molecular chaperone Hsp90 is overexpressed in prostate cancer (PCa) and is responsible for the folding, stabilization and maturation of multiple oncoproteins, which are implicated in PCa progression. Compared to first-in-class Hsp90 inhibitors such as 17-allylamino-demethoxygeldanamycin (17-AAG) that were clinically ineffective, second generation inhibitor AUY922 has greater solubility and efficacy. Here, transcriptomic and proteomic analyses of patient-derived PCa explants identified cytoskeletal organization as highly enriched with AUY922 treatment...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29380669/cerebral-blood-flow-measured-by-positron-emission-tomography-during-normothermic-cardiopulmonary-bypass-an-experimental-porcine-study
#5
Sisse Anette Thomassen, Benedict Kjærgaard, Aage Kristian Olsen Alstrup, Ole Lajord Munk, Jørgen Frøkiær, Anders Larsson, Bodil Steen Rasmussen
BACKGROUND: Mean arterial blood pressure (MAP) and/or pump flow during normothermic cardiopulmonary bypass (CPB) are the most important factors of cerebral perfusion. The aim of this study was to explore the influence of CPB blood flow on cerebral blood flow (CBF) measured by dynamic positron emission tomography (PET) using 15O-labelled water with no pharmacological interventions to maintain the MAP. METHODS: Eight pigs (69-71 kg) were connected to normothermic CPB...
January 1, 2018: Perfusion
https://www.readbyqxmd.com/read/29364879/mitochondrial-translation-requires-folate-dependent-trna-methylation
#6
Raphael J Morscher, Gregory S Ducker, Sophia Hsin-Jung Li, Johannes A Mayer, Zemer Gitai, Wolfgang Sperl, Joshua D Rabinowitz
Folates enable the activation and transfer of one-carbon units for the biosynthesis of purines, thymidine and methionine. Antifolates are important immunosuppressive and anticancer agents. In proliferating lymphocytes and human cancers, mitochondrial folate enzymes are particularly strongly upregulated. This in part reflects the need for mitochondria to generate one-carbon units and export them to the cytosol for anabolic metabolism. The full range of uses of folate-bound one-carbon units in the mitochondrial compartment itself, however, has not been thoroughly explored...
January 24, 2018: Nature
https://www.readbyqxmd.com/read/29325736/differential-association-of-dennd1agenetic-variants-with-polycystic-ovary-syndrome-in-tunisian-but-not-bahraini-arab-women
#7
Meriem Dallel, Sameh Sarray, Zeineb Douma, Feten Hachani, Abrar K Al-Ansari, Dhafer B Letaifa, Touhami Mahjoub, Wassim Y Almawi
BACKGROUND AND AIM: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and results from interaction between modifiable and non-modifiable factors, including genetic predisposition. Previous genome-wide association studies and meta-analysis identified DENND1A as PCOS susceptibility locus in some, but not all populations. We investigated whether the association of DENND1A gene variants with PCOS was similar between Tunisian and Bahraini Arab women. SUBJECTS AND METHODS: This was retrospective case-control study...
January 8, 2018: Gene
https://www.readbyqxmd.com/read/29317342/imaging-guided-photo-therapeutic-nanoporphyrin-synergized-hsp90-inhibitor-in-patient-derived-xenograft-bladder-cancer-model
#8
Qilai Long, Tzu-Yin Lin, Yee Huang, Xiaocen Li, Ai-Hong Ma, Hongyong Zhang, Randy Carney, Susan Airhart, Kit S Lam, Chong-Xian Pan, Yuanpei Li
Photodynamic therapy is a promising and effective non-invasive therapeutic approach for the treatment of bladder cancers. Therapies targeting HSP90 have the advantage of tumor cell selectivity and have shown great preclinical efficacy. In this study, we evaluated a novel multifunctional nanoporphyrin platform loaded with an HSP90 inhibitor 17AAG (NP-AAG) for use as a multi-modality therapy against bladder cancer. NP-AAG was efficiently accumulated and retained at bladder cancer patient-derived xenograft (PDX) over 7 days...
January 6, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29315013/on-the-evolution-of-bile-salts-and-the-farnesoid-x-receptor-in-vertebrates
#9
Kim Frisch, Aage Kristian Olsen Alstrup
In recent decades, our knowledge of bile salts has undergone a vast development, and bile salts are now known not only for their detergent properties that aid in the absorption of dietary lipids but also for their interaction with specific nuclear and membrane receptors. In particular, it has been realized that the response of the farnesoid X receptor (FXR) to bile acids provides a signal bridge between the liver and small intestine, controlling the intracellular levels, biosynthesis, and enterohepatic circulation of bile acids...
March 2018: Physiological and Biochemical Zoology: PBZ
https://www.readbyqxmd.com/read/29297949/effect-of-17-allylamino-17-demethoxygeldanamycin-17-aag-on-akt-protein-expression-is-more-effective-in-head-and-neck-cancer-cell-lineages-that-retain-pten-protein-expression
#10
Flávia Sirotheau Corrêa Pontes, Hélder Antônio Rebelo Pontes, Lucas Lacerda de Souza, Adriana Souza de Jesus, Andrea Maia Correa Joaquim, Ligia Akiko Ninokata Miyahara, Felipe Paiva Fonseca, Décio Dos Santos Pinto Júnior
OBJECTIVES: The aim of this study was to evaluate the expression of Akt, PTEN, Mdm2 and p53 proteins in three different head and neck squamous cell carcinoma (HNSCC) cell lines (HN6, HN19 and HN30), all of them treated with epidermal growth factor (EGF) and 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of Hsp90 protein. MATERIAL AND METHODS: Immunofluorescence and western blot were performed in order to analyze the location and quantification, respectively, of proteins under the action 17-AAG and EGF...
January 3, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29294741/factors-associated-with-police-decisions-on-immediate-responses-to-intimate-partner-violence
#11
Merete Berg Nesset, Johan Håkon Bjørngaard, Jim Aage Nøttestad, Richard Whittington, Cecilie Lynum, Cand Psychol, Tom Palmstierna
Police officers are often the first responders to intimate partner violence. The aim of the study was to examine the association between structured police assessments on-site in cases of intimate partner violence, and decisions about immediate arrest of the perpetrator and/or relocation of the victim. Data were extracted from police reports on 124 emergency visits in cases of intimate partner violence perpetrated by men toward women. Six out of totally 15 items of the intimate partner violence risk assessment measure B-SAFER were used by the front line police officers as the basis for decisions on whether or not to arrest the perpetrator or relocate the victim...
May 1, 2017: Journal of Interpersonal Violence
https://www.readbyqxmd.com/read/29280036/seronegative-autoimmune-autonomic-neuropathy-a-distinct-clinical-entity
#12
Elisabeth P Golden, Meredith A Bryarly, Steven Vernino
PURPOSE: Autoimmune autonomic ganglionopathy (AAG) is associated with ganglionic acetylcholine receptor (gAChR) antibodies. We describe a similar but distinct series of patients with autoimmune autonomic failure lacking this antibody. METHODS: Retrospective chart review. RESULTS: Six patients presented with subacute autonomic failure, seronegative for gAChR antibodies. Orthostatic hypotension and gastrointestinal complaints were common. Autonomic testing revealed predominant sympathetic failure and no premature pupillary redilation...
December 26, 2017: Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society
https://www.readbyqxmd.com/read/29273001/how-general-practitioners-perceive-and-assess-self-care-in-patients-with-multiple-chronic-conditions-a-qualitative-study
#13
Mads Aage Toft Kristensen, Bibi Hølge-Hazelton, Frans Boch Waldorff, Ann Dorrit Guassora
BACKGROUND: It is not known how general practitioners (GPs) perceive the concept of self-care and how they assess self-care ability in patients with multiple chronic conditions. As a part of the strategy to improve the care of people living with chronic conditions, disease management programs in Denmark require GPs and other health care workers to assess and support patients' self-care ability. The aim of the present study was to explore GPs' perceptions and assessment of self-care ability in patients with multiple chronic conditions who have difficulty following a given treatment...
December 22, 2017: BMC Family Practice
https://www.readbyqxmd.com/read/29248972/pharmacological-targeting-of-hsp90-with-17-aag-induces-apoptosis-of-myogenic-cells-through-activation-of-the-intrinsic-pathway
#14
Akira Wagatsuma, Yuzo Takayama, Takayuki Hoshino, Masataka Shiozuka, Shigeru Yamada, Ryoichi Matsuda, Kunihiko Mabuchi
We have shown that pharmacological inhibition of HSP90 ATPase activity induces apoptosis of myoblasts during their differentiation. However, the signaling pathways remain not fully characterized. We report that pharmacological targeting of HSP90 with 17-AAG activates the intrinsic pathway including caspase-dependent and caspase-independent pathways. 17-AAG induces the typical apoptotic phenotypes including PARP cleavage, chromatin condensation, and nuclear fragmentation with mitochondrial release of cytochrome c, Smac/DIABLO, procaspase-9 processing, and caspase-3 activation...
December 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29243556/-preferences-of-aaa-aag-codon-recognition-by-modified-nucleosides-%C3%AF-m5s2u34-and-t6a37-present-in-trnalys
#15
Kailas D Sonawane, Asmita S Kamble, Prayagraj M Fandilolu
Deficiency of 5-taurinomethyl-2-thiouridine, τm5s2U at the 34th 'wobble' position in tRNALys causes MERRF (Myoclonic Epilepsy with Ragged Red Fibers), a neuromuscular disease. This modified nucleoside of mt tRNALys, recognizes AAA/AAG codons during protein biosynthesis process. Its preference to identify cognate codons has not been studied at the atomic level. Hence, multiple MD simulations of various molecular models of anticodon stem loop (ASL) of mt tRNALys in presence and absence of τm5s2U34 and N6-threonylcarbamoyl adenosine (t6A37) along with AAA and AAG codons have been accomplished...
December 15, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29238017/-the-interface-between-the-immune-system-and-autonomic-nervous-system
#16
Shunya Nakane, Akihiro Mukaino, Yukio Ando
  The nervous system and the immune system are two major systems in human body. Although it was revealed these two systems correlated, the control of immune cell dynamics by the nervous system has come to draw a lot of attention at the present time. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in several animal models. One well-characterized cytokine-inhibiting mechanism, termed the "inflammatory reflex", is dependent upon vagus nerve stimulation that inhibits cytokine production and attenuates the inflammation...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29235746/clinical-problem-solving-a-tobacco-merchant-who-can-t-spit
#17
Sandra Benizri, Nancy Agmon-Levin, Noam D Kitrey, Dan Carter, Elinor Goshen, Yehonathan Sharabi
A 47 year old man presented with a combination of dry mouth and lightheadedness while standing. His medical background was unremarkable except for cigarette smoking and hyperlipidemia. Sjögren's syndrome was ruled out, and he was referred for evaluation of orthostatic hypotension, which by then included syncopal episodes and injuries. Additional symptoms included dry eyes, constipation, reduced sweating, and erectile dysfunction. After excluding medications and structural cardiac abnormalities as causes of orthostatic hypotension, a clinical autonomic evaluation was performed...
December 2017: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/29235458/the-ideal-harvest-time-for-seeds-of-hybrid-maize-zea-mays-l-xy335-and-zd958-produced-in-multiple-environments
#18
Riliang Gu, Li Li, Xiaolin Liang, Yanbo Wang, Tinglu Fan, Ying Wang, Jianhua Wang
To identify the ideal harvest time (IHT) for the seed production of XY335 and ZD958, six seed-related traits were evaluated in seeds harvested at 11 harvest stages in 8 environments. Standard germination (SG), accelerated aging germination (AAG) and cold test germination (CTG) were vigor traits; hundred-seed weight (HSW) and seed moisture content (SMC) were physiological traits; and ≥10 °C accumulated temperature from pollination to harvest (AT10ph) was an ecological trait. All the traits were significantly affected by harvest stage...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29228590/precision-and-recall-oncology-combining-multiple-gene-mutations-for-improved-identification-of-drug-sensitive-tumours
#19
Stefan Naulaerts, Cuong C Dang, Pedro J Ballester
Cancer drug therapies are only effective in a small proportion of patients. To make things worse, our ability to identify these responsive patients before administering a treatment is generally very limited. The recent arrival of large-scale pharmacogenomic data sets, which measure the sensitivity of molecularly profiled cancer cell lines to a panel of drugs, has boosted research on the discovery of drug sensitivity markers. However, no systematic comparison of widely-used single-gene markers with multi-gene machine-learning markers exploiting genomic data has been so far conducted...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207898/nr3c1-gene-polymorphisms-are-associated-with-steroid-resistance-in-patients-with-primary-nephrotic-syndrome
#20
Jie Liu, Zan Wan, Qianqian Song, Zhi Li, Yijing He, Yongjun Tang, Wanying Xie, Yanyun Xie, Jun Zhang
AIM: The aim of this study was to investigate the role of SNPs of genes involved in the glucocorticoid pathway in the development of steroid resistance in patients with primary nephrotic syndrome. METHODS: Sequenom MassARRAY method was used to sequence 25 SNP genotypes in 154 patients. The frequency distribution of the genotypes was compared between patients with steroid-sensitive nephrotic syndrome and those with steroid-resistant nephrotic syndrome. RESULTS: NR3C1 rs6196 G allele carriers had a decreased risk of steroid resistance compared with that of the A allele carriers...
December 6, 2017: Pharmacogenomics
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