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https://www.readbyqxmd.com/read/29777910/differentially-expressed-novel-alternatively-spliced-transcript-variant-of-tumor-suppressor-stk11-gene-in-mouse
#1
Hassan Mubarak Ishqi, Tarique Sarwar, Mohammed Amir Husain, Sayeed Ur Rehman, Mohammad Tabish
Serine/threonine kinase 11 (STK11) is a protein kinase that is encoded by Stk11 gene located on chromosome 19 and 10 in humans and mouse respectively. It acts as a master kinase of adenine monophosphate-activated protein kinase (AMPK) pathway that coordinates the regulation of cellular energy metabolism and cell division. STK11 exerts effect by activating more than 14 kinases including AMPK and AMPK-related kinases. It is also known to regulate cell polarity and acts as tumor suppressor. Alternative splicing of pre-mRNA is a mechanism which results in multiple transcript variants of a single gene...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29777907/novel-snps-of-wnk1-and-akr1c3-are-associated-with-preeclampsia
#2
Cheng-Juan Sun, Lin Li, Xueyan Li, Wei-Yuan Zhang, Xiao-Wei Liu
Preeclampsia is a hypertensive disorder of pregnancy and is one of the most common causes of poor perinatal outcomes. Preeclampsia increases the risk of hypertension in the future. Variants of WNK1 (lysine deficient protein kinase 1), ADRB2 (β2 adrenergic receptor), NEDD4L (ubiquitin-protein ligase NEDD4-like), KLK1 (kallikrein 1) contribute to hypertension, and AKR1C3 (aldo-keto reductase family1 member C3), is associated with preeclampsia. The association of single nucleotide polymorphisms (SNPs) in these five candidate preeclampsia susceptibility genes and the related traits in Chinese individuals were investigated...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29777861/in-vitro-activity-characterization-of-the-tomato-snrk1-complex-proteins
#3
Dongyin Su, Timothy P Devarenne
Plant Sucrose non-Fermenting 1-Related Protein Kinase1 (SnRK1) complexes are members of the Snf1/AMPK/SnRK protein kinase family and play important roles in many aspects of metabolism. In tomato (Solanum lycopersicum, Sl), only one α-subunit of the SnRK1 complex, SlSnRK1.1, has been characterized to date. In this study, the phylogenetic placement and in vitro kinase activity of a second tomato SnRK1 α-subunit, SlSnRK1.2, were characterized. Interestingly, in the phylogenetic analysis of SnRK1 sequences from monocots and dicots SlSnRK1...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777765/in-vitro-and-in-vivo-evaluation-of-an-oral-sustained-release-hepatoprotective-caffeine-loaded-w-o-pickering-emulsion-formula-containing-wheat-germ-oil-and-stabilized-by-magnesium-oxide-nanoparticles
#4
Heba Elmotasem, Hala K Farag, Abeer A A Salama
The objective of this study was to innovate an effective oral sustained release hepatoprotective formula for - the water soluble drug - caffeine. Caffeine is rapidly absorbed and eliminated which dictates frequent administration to achieve adequate therapeutic effect. A w/o Pickering emulsion incorporating caffeine in the internal phase was primed. It contained wheat germ oil and was stabilized by synthesized magnesium oxide nanoparticles (MgO NPs). Components selection was based on their antioxidant, hepatoprotective and anticarcinogenic effects...
May 16, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29777684/repositioning-of-anti-cancer-drug-candidate-azd7762-to-an-anti-allergic-drug-suppressing-ige-mediated-mast-cells-and-allergic-responses-via-the-inhibition-of-lyn-and-fyn
#5
Young Hwan Park, Do Kyun Kim, Hyun Woo Kim, Hyuk Soon Kim, Dajeong Lee, Min Bum Lee, Keun Young Min, Jimo Koo, Su Jeong Kim, Changhee Kang, Young Mi Kim, Hyung Sik Kim, Wahn Soo Choi
Mast cells are critical effector cells in IgE-mediated allergic responses. The aim of this study was to investigate the anti-allergic effects of 3-[(aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-thiophenecarboxamide (AZD7762) in vitro and in vivo. AZD7762 inhibited the antigen-stimulated degranulation from RBL-2H3 (IC50 , ∼ 27.9 nM) and BMMCs (IC50 , ∼ 99.3 nM) in a dose-dependent manner. AZD7762 also inhibited the production of TNF-α and IL-4. As the mechanism of its action, AZD7762 inhibited the activation of Syk and its downstream signaling proteins, such as Linker of activated T cells (LAT), phospholipase (PL) Cγ1, Akt, and mitogen-activated protein (MAP) kinases (Erk1 / 2, p38, and JNK) in mast cells...
May 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29777529/pharmacokinetics-of-ads-5102-amantadine-extended-release-capsules-administered-once-daily-at-bedtime-for-the-treatment-of-dyskinesia
#6
Robert A Hauser, Rajesh Pahwa, William A Wargin, Cindy J Souza-Prien, Natalie McClure, Reed Johnson, Jack T Nguyen, Rajiv Patni, Gregory T Went
BACKGROUND: Preclinical and clinical studies suggest amantadine immediate-release (IR) may reduce dyskinesia in Parkinson's disease (PD), although higher doses are associated with increased CNS adverse events (AEs). ADS-5102 is an extended release amantadine capsule formulation, designed for once-daily dosing at bedtime (qhs) to provide high concentrations upon waking and throughout the day, with lower concentrations in the evening. The pharmacokinetics (PK) of ADS-5102 were assessed in two phase I studies in healthy subjects, and a blinded, randomized phase II/III dose-finding study in PD patients...
May 18, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29777511/a-case-of-pancake-kidney-with-a-single-ureter-in-the-retroperitoneal-space
#7
Kasuga Horai, Munekazu Naito, Tomiko Yakura, Yuka Furuya, Yusuke Ohmichi, Mika Ohmichi, Takayoshi Miyaki, Takashi Nakano
The pancake kidney (PK) is a rare type of renal anomaly in which both kidneys completely fuse without an isthmus. In the previous reports, PKs have double ureters and are located in the pelvic cavity. We encountered a rare case of PK with a single ureter, which is located in the left retroperitoneal space, in a 95-year-old female cadaver, which was detected during a dissection course. In our case, the major calyces joined to form a single renal pelvis, which continued as a single ureter. To the best of our knowledge, this is the first report on PK with a single ureter that is located not in the pelvic cavity but in the retroperitoneal space...
May 18, 2018: Anatomical Science International
https://www.readbyqxmd.com/read/29777502/oxi1-kinase-plays-a-key-role-in-resistance-of-arabidopsis-towards-aphids-myzus-persicae
#8
Tahsin Shoala, Martin G Edwards, Marc R Knight, Angharad M R Gatehouse
Plants have co-evolved with a diverse array of pathogens and insect herbivores and so have evolved an extensive repertoire of constitutive and induced defence mechanisms activated through complex signalling pathways. OXI1 kinase is required for activation of mitogen-activated protein kinases (MAPKs) and is an essential part of the signal transduction pathway linking oxidative burst signals to diverse downstream responses. Furthermore, changes in the levels of OXI1 appear to be crucial for appropriate signalling...
May 17, 2018: Transgenic Research
https://www.readbyqxmd.com/read/29777026/endosomal-tlr3-tlr7-and-tlr8-control-neuronal-morphology-through-different-transcriptional-programs
#9
Yun-Fen Hung, Chiung-Ya Chen, Yi-Chun Shih, Hsin-Yu Liu, Chiao-Ming Huang, Yi-Ping Hsueh
Neuroinflammation is associated with diverse neurological disorders. Endosomal Toll-like receptors (TLRs) including TLR3, TLR7, and TLR8 cell-autonomously regulate neuronal differentiation. However, the mechanisms by which these three TLRs affect neuronal morphology are unclear. In this study, we compare these TLRs in mouse neurons. By combining in vitro neuronal cultures, in utero electroporation, and transcriptomic profiling, we show that TLR8, TLR7, and TLR3 promote dendritic pruning via MYD88 signaling...
May 18, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29776748/conserved-degradation-of-orthologous-rlcks-regulates-immune-homeostasis
#10
Jacqueline Monaghan
Arabidopsis (Arabidopsis thaliana) AtBIK1 and rice (Oryza sativa) OsRLCK176 are orthologous receptor-like cytoplasmic kinases involved in immune signaling. Recent studies indicate that proteasomal turnover of these kinases is regulated by orthologous Ca2+ -dependent protein kinases AtCPK28 and OsCPK4, revealing conserved interplay between phosphorylation and ubiquitination in immune homeostasis.
May 15, 2018: Trends in Plant Science
https://www.readbyqxmd.com/read/29776710/pharmacokinetics-pharmacodynamics-computer-decision-support-technologies-and-antimicrobial-stewardship-the-compass-and-rudder
#11
REVIEW
Robert C Owens, Catharine C Bulik, David R Andes
The first guidelines for conducting antimicrobial stewardship in the hospitalized setting were published in 2007. These guidelines recommend that stewardship programs employ the science of pharmacokinetics-pharmacodynamics (PK-PD) as well as adopting computerized decision support technologies when possible. The United States Food and Drug Administration have adopted PK-PD as a cornerstone in the evaluation of antimicrobial agents during clinical development. The core principles of PK-PD center around describing the relationship between drug exposure indexed to the susceptibility of the infecting bacterial pathogen and patient response...
April 13, 2018: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29776017/pharmacokinetics-and-c-reactive-protein-modelling-of-anti-il-6-antibody-pf-04236921-in-healthy-volunteers-and-patients-with-autoimmune-disease
#12
Cheryl Li, Satoshi Shoji, Jean Beebe
AIMS: The purpose of this study was to characterize pharmacokinetics (PK) of PF-04236921, a novel anti-IL-6 monoclonal antibody, and its pharmacokinetics/pharmacodynamics (PK/PD) relationship on serum C-Reactive Protein (CRP) in healthy volunteers and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Crohn's disease (CD) METHODS: Population modelling analyses were conducted using nonlinear mixed effects modelling. Data from 2 phase 1 healthy volunteer studies, a phase 1 RA study, a Phase 2 CD study, and a Phase 2 SLE study were included...
May 18, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29775996/interplay-between-adenylate-metabolizing-enzymes-and-amp-activated-protein-kinase
#13
REVIEW
Marcella Camici, Simone Allegrini, Maria Grazia Tozzi
Purine nucleotides are involved in a variety of cellular functions, such as energy storage and transfer, and signalling, in addition to being the precursors of nucleic acids and cofactors of many biochemical reactions. They can be generated through two separate pathways, the de novo biosynthesis pathway and the salvage pathway. De novo purine biosynthesis leads to the formation of IMP, from which the adenylate and guanylate pools are generated by two additional steps. The salvage pathways utilize hypoxanthine, guanine and adenine to generate the corresponding mononucleotides...
May 18, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29775756/pkm2-a-potential-target-for-regulating-cancer
#14
REVIEW
Yu-Huan Li, Xiao-Feng Li, Jia-Tao Liu, Hua Wang, Lu-Lu Fan, Jun Li, Guo-Ping Sun
Aberrated glucose metabolism is a key future of cancer cells. Unlike normal cells, tumor cells favor glycolysis even in the presence of sufficient oxygen. Pyruvate kinase (PK), a key glucose metabolic enzyme, converts phosphoenolpyruvate (PEP) to pyruvate by transferring the high-energy phosphate group to adenosine diphosphate (ADP) to produce adenosine triphosphate (ATP). Pyruvate kinase M2 (PKM2), one of the four isozyme of PK, which universally expressed in rapidly proliferating cells such as embryonic cells and cancer cells...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775750/the-effects-of-capn1-gene-inactivation-on-the-differential-expression-of-genes-in-skeletal-muscle
#15
William T Olive, Brittney N Keel, Amanda K Lindholm-Perry, Justyna Horodyska, Andrew P Foote
Protein turnover is required for muscle growth and regeneration and several proteolytic enzymes, including the calpains, degrade myofibrillar proteins during this process. In a previous experiment, phenotypic differences were observed between μ-calpain knockout (KO) and wild type (WT) mice, including nutrient accretion and fiber type differences. These changes were particularly evident as the animals aged. Thus, we utilized 18 mice (9 KO and 9 WT) to compare transcript abundance to identify differentially expressed genes (DEGs) at 52 wk of age...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775743/redox-regulation-of-protein-kinase-c-by-selenometabolites-and-selenoprotein-thioredoxin-reductase-limits-cancer-prevention-by-selenium
#16
REVIEW
Rayudu Gopalakrishna, Usha Gundimeda, Sarah Zhou, Bui Helena, Arne Holmgren
The cancer-preventive mechanism of selenium should address the way low concentrations of selenometabolites react with cellular targets without being diffused from the sites of generation, the way selenium selectively kills tumor cells, and the intriguing U-shaped curve that is seen with dietary supplementation of selenium and cancer prevention. Protein kinase C (PKC), a receptor for tumor promoters, is well suited for this mechanism. Due to the catalytic redox cycle, low concentrations of methylselenol, a postulated active metabolite of selenium, react with the tumor-promoting lipid hydroperoxide bound to PKC to form methylseleninic acid (MSA), which selectively reacts with thiol residues present within the vicinity of the PKC catalytic domain to inactivate it...
May 15, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29775667/identification-of-novel-hla-a11-restricted-t-cell-epitopes-in-the-ebola-virus-nucleoprotein
#17
Dan Li, Pei Li, Nianping Song, Yuting Jiang, Yang Zeng, Guangyu Zhao, Yunzhi Fa, Huahu Ye, Yuchun Lone, Yusen Zhou, Shihui Sun, Lin Zeng
The Ebola virus (EBOV) is a very contagious virus that is highly fatal in humans and animals. The largest epidemic was in West Africa in 2014, in which over 11,000 people died. However, to date, there are no licensed vaccines against it. Studies show that CD4+ and CD8+ T-cell responses, especially cytotoxic T-lymphocyte (CTL) responses, play key roles in protecting individuals from EBOV infection. Since HLA-restricted epitope vaccines are likely to be effective and safe immunization strategies for infectious diseases, the present study screened for CTL epitopes in the EBOV-nucleoprotein that are restricted by HLA-A11 (a common allele in Chinese people)...
May 15, 2018: Microbes and Infection
https://www.readbyqxmd.com/read/29775492/a-mitogen-activated-protein-kinase-phosphatase-influences-grain-size-and-weight-in-rice
#18
Ran Xu, Haiyue Yu, Junmin Wang, Penggen Duan, Baolan Zhang, Jing Li, Yu Li, Jinsong Xu, Jia Lyu, Na Li, Tuanyao Chai, Yunhai Li
Grain size and weight are directly associated with grain yield in crops. However, the molecular mechanisms that set final grain size and weight remain largely unknown. Here, we characterize two large grain mutants, large grain8-1 (large8-1) and large grain8-2 (large8-2). LARGE8 encodes the mitogen-activated protein kinase phosphatase1 (OsMKP1). Loss of function mutations in OsMKP1 results in large grains, while overexpression of OsMKP1 leads to small grains. OsMKP1 determines grain size by restricting cell proliferation in grain hulls...
May 18, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29775417/targeting-histone-methyltransferase-enhancer-of-zeste-homolog-2-inhibits-renal-epithelial-mesenchymal-transition-and-attenuates-renal-fibrosis
#19
Xiaoxu Zhou, Chongxiang Xiong, Evelyn Tolbert, Ting C Zhao, George Bayliss, Shougang Zhuang
Enhancer of zeste homolog-2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. Its role in renal epithelial-mesenchymal transition (EMT) remains unknown. In this study, we found that EZH2 and H3K27me3 were highly expressed in mouse kidney with unilateral ureteral obstruction and cultured mouse kidney proximal tubular (TKPT) cells undergoing EMT. Inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) attenuated renal fibrosis, which was associated with preserving E-cadherin expression and inhibiting Vimentin up-regulation in the obstructed kidney...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29775175/hiv-induced-matrix-metalloproteinase-9-activation-through-mitogen-activated-protein-kinase-signalling-promotes-hsv-1-cell-to-cell-spread-in-oral-epithelial-cells
#20
Irna Sufiawati, Sharof M Tugizov
We have shown that cell-free HIV-1 and viral proteins tat and gp120 activate mitogen-activated protein kinases (MAPKs) in tonsil epithelial cells, disrupting their tight and adherens junctions. This causes liberation of the HSV-1 receptor nectin-1 from assembled adherens junctions, leading to promotion of HSV-1 infection and spread. In the present study, we show that HIV-associated activation of MAPK leads to upregulation of transcription factor NF-κB and matrix metalloproteinase-9 (MMP-9). This induces the disruption of tight and adherens junctions, increasing HSV-1 cell-to-cell spread...
May 18, 2018: Journal of General Virology
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