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https://www.readbyqxmd.com/read/28324067/gestational-protein-restriction-impairs-glucose-disposal-in-the-gastrocnemius-muscles-of-female-rats
#1
C S Blesson, V Chinnathambi, S Kumar, C Yallampalli
Gestational low protein (LP) diet causes hyperglycemia and insulin resistance in adult offspring but the mechanism is not clearly understood. In this study, we explored the role of insulin signaling in gastrocnemius muscles of gestational LP exposed female offspring. Pregnant rats were fed control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery. Normal diet was given to mothers after delivery and to pups after weaning until necropsy. Offspring were euthanized at 4 months and gastrocnemius muscles were treated with insulin ex vivo for 30 min...
January 30, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323963/an-antibody-to-notch2-reverses-the-osteopenic-phenotype-of-hajdu-cheney-mutant-male-mice
#2
Ernesto Canalis, Archana Sanjay, Jungeun Yu, Stefano Zanotti
Notch receptors play a central role in skeletal development and bone remodeling. Hajdu Cheney Syndrome (HCS), a disease characterized by osteoporosis and fractures, is associated with gain-of-NOTCH2 function mutations. To study HCS, we created a mouse model harboring a point 6955C>T mutation in the Notch2 locus upstream of the proline (P), glutamic acid (E), serine (S) and threonine (T) domain leading to a Q2319X change at the amino acid level. Notch2Q2319X heterozygous mutants exhibited cancellous and cortical bone osteopenia...
January 31, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323876/pim1-minicircle-as-a-therapeutic-treatment-for-myocardial-infarction
#3
Nan Liu, Bingyan J Wang, Kathleen M Broughton, Roberto Alvarez, Sailay Siddiqi, Rebeca Loaiza, Nicky Nguyen, Pearl Quijada, Natalie Gude, Mark A Sussman
PIM1, a pro-survival gene encoding a serine/ threonine kinase, influences cell proliferation and survival. Modification of cardiac progenitor cells (CPCs) or cardiomyocytes with PIM1 using a lentivirus-based delivery method showed long-term improved cardiac function after myocardial infarction (MI). However, lentivirus based delivery methods have stringent FDA regulation with respect to clinical trials. To provide an alternative and low risk PIM1 delivery method, this study examined the use of a non-viral modified plasmid-minicircle (MC) as a vehicle to deliver PIM1 into mouse CPCs (mCPCs) in vitro and the myocardium in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28318835/improvement-in-mismatch-negativity-generation-during-d-serine-treatment-in-schizophrenia-correlation-with-symptoms
#4
Joshua T Kantrowitz, Michael L Epstein, Migyung Lee, Nayla Lehrfeld, Karen A Nolan, Constance Shope, Eva Petkova, Gail Silipo, Daniel C Javitt
BACKGROUND: Deficits in N-methyl-d-aspartate-type (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia. The efficacy of NMDAR agonists in the treatment of persistent symptoms of schizophrenia has been variable, potentially reflecting limitations in functional target engagement. We recently demonstrated significant improvement in auditory mismatch negativity (MMN) with once-weekly treatment with d-serine, a naturally occurring NMDAR glycine-site agonist. This study investigates effects of continuous (daily) NMDAR agonists in schizophrenia/schizoaffective disorder...
March 17, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28318058/nuclear-codon-reassignments-in-the-genomics-era-and-mechanisms-behind-their-evolution
#5
REVIEW
Martin Kollmar, Stefanie Mühlhausen
The canonical genetic code ubiquitously translates nucleotide into peptide sequence with several alterations known in viruses, bacteria, mitochondria, plastids, and single-celled eukaryotes. A new hypothesis to explain genetic code changes, termed tRNA loss driven codon reassignment, has been proposed recently when the polyphyly of the yeast codon reassignment events has been uncovered. According to this hypothesis, the driving force for genetic code changes are tRNA or translation termination factor loss-of-function mutations or loss-of-gene events...
March 20, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28318015/plasma-levels-of-masp-1-masp-3-and-map44-in-patients-with-type-2-diabetes-influence-of-glycaemic-control-body-composition-and-polymorphisms-in-the-masp1-gene
#6
Sara Skov Krogh, Charlotte Brinck Holt, Rudi Steffensen, Kristian Løkke Funck, Pernille Høyem, Esben Laugesen, Per Løgstrup Poulsen, Steffen Thiel, Troels Krarup Hansen
Mounting evidence indicates that adverse activation of the complement system plays a role in the development of diabetic vascular complications. Plasma levels of the complement proteins mannan-binding lectin (MBL) and its associated serine proteases (MASP-1 and MASP-2) are elevated in diabetes. We hypothesised that single nucleotide polymorphisms (SNPs) in the MASP1 gene may contribute to altered plasma levels of the belonging gene products; MASP-1, MASP-3 and mannan-binding lectin-associated protein of 44 kDa (MAp44) in patients with type 2 diabetes...
March 20, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28317204/cockroach-allergen-serine-proteinases-isolation-sequencing-and-signalling-via-proteinase-activated-receptor-2-par2
#7
Danny J Polley, Koichiro Mihara, Rithwik Ramachandran, Harissios Vliagoftis, Bernard Renaux, Mahmoud Saifeddine, Michael O Daines, Scott Boitano, Morley D Hollenberg
BACKGROUND: Allergy to the German cockroach (Blattella germanica) is a significant asthma risk factor for inner-city communities. Cockroach, like other allergens, contains trypsin-like enzyme activity that contributes to allergenicity and airway inflammation by activating proteinase-activated receptors (PARs). To date, the enzymes responsible for the proteolytic activity of German cockroach allergen have not been characterized. OBJECTIVES: We aimed to identify, isolate and characterize the trypsin-like proteinases in German cockroach allergen extracts used for clinical skin tests...
March 20, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28315663/enhancing-the-catalytic-deamination-activity-of-apobec3c-is-insufficient-to-inhibit-vif-deficient-hiv-1
#8
Ananda Ayyappan Jaguva Vasudevan, Henning Hofmann, Dieter Willbold, Dieter Häussinger, Bernd W Koenig, Carsten Münk
The retroviral restriction factors of the APOBEC3 (A3) cytidine deaminase family catalyze the deamination of cytidines in single-stranded viral DNA. APOBEC3C (A3C) is a strong antiviral factor against viral infectivity factor (vif)-deficient simian immunodeficiency (SIV) Δvif, however, a weak inhibitor against human immunodeficiency virus (HIV)-1 for reasons unknown. The precise link between the antiretroviral effect of A3C and its catalytic activity is incompletely understood. Here we show that the S61P mutation in human A3C (A3C...
March 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28315636/pembrolizumab-for-metastatic-melanoma-in-a-renal-allograft-recipient-with-subsequent-graft-rejection-and-treatment-response-failure-a-case-report
#9
Vineet Kwatra, Narayan V Karanth, Kelum Priyadarshana, Michail Charakidis
BACKGROUND: Transplant patients were excluded from the pivotal phase III trials of checkpoint inhibitors in metastatic melanoma. The efficacy and toxicity profiles of checkpoint inhibitors in this cohort of patients are not well described. To the best of our knowledge, this is the first case report of a renal transplant patient with stage IV melanoma treated with a programmed cell death protein 1 checkpoint inhibitor that led to both treatment failure and renal graft rejection. CASE PRESENTATION: We present a case of a 58-year-old white man with a long-standing cadaveric renal transplant who was diagnosed with a B-Raf Proto-Oncogene, Serine/Threonine Kinase wild-type metastatic melanoma...
March 19, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28315597/discovery-of-n-3-5-3-acrylamido-4-morpholine-4-carbonyl-phenyl-amino-1-methyl-6-oxo-1-6-dihydropyridin-3-yl-2-methylphenyl-4-tert-butyl-benzamide-chmfl-btk-01-as-a-highly-selective-irreversible-bruton-s-tyrosine-kinase-btk-inhibitor
#10
Qianmao Liang, Yongfei Chen, Kailin Yu, Cheng Chen, Shouxiang Zhang, Aoli Wang, Wei Wang, Hong Wu, Xiaochuan Liu, Beilei Wang, Li Wang, Zhenquan Hu, Wenchao Wang, Tao Ren, Shanchun Zhang, Qingsong Liu, Cai-Hong Yun, Jing Liu
Currently there are several irreversible BTK inhibitors targeting Cys481 residue under preclinical or clinical development. However, most of these inhibitors also targeted other kinases such as BMX, JAK3, and EGFR that bear the highly similar active cysteine residues. Through a structure-based drug design approach, we discovered a highly potent (IC50: 7 nM) irreversible BTK inhibitor compound 9 (CHMFL-BTK-01), which displayed a high selectivity profile in KINOMEscan (S score (35) = 0.00) among 468 kinases/mutants at the concentration of 1 μM...
March 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28315488/sorafenib-as-a-potential-strategy-for-refractory-pulmonary-arterial-hypertension
#11
Gou Kimura, Masaharu Kataoka, Takumi Inami, Keiichi Fukuda, Hideaki Yoshino, Toru Satoh
Sorafenib is an inhibitor of multi-kinases including tyrosine and serine/threonine kinases. We investigated the efficacy and safety of sorafenib for the treatment of patients with refractory pulmonary arterial hypertension (PAH). Sorafenib was started in 9 patients (7 with idiopathic PAH, 2 with pulmonary veno-occlusive disease) who had severe PAH and right heart failure, in spite of treatment with vasodilators specific for PAH. Sorafenib was started as an add-on therapy at a dose of 50 or 100 mg/day, and increased to 100-400 mg/day...
March 14, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315454/astragaloside-iv-attenuates-lead-acetate-induced-inhibition-of-neurite-outgrowth-through-activation-of-akt-dependent-nrf2-pathway-in-vitro
#12
Chunlei Yu, Siwen Pan, Miaoxian Dong, Yingcai Niu
Recently, oxidative stress is strongly associated with lead (Pb)-induced neurotoxicity. We reported previously that Astragaloside IV (AS-IV) possesses potent antioxidant properties. Here, we evaluate the hypothesis that AS-IV attenuates lead acetate (PbAc)-mediated inhibition of neurite outgrowth might mainly result from its antioxidant property via serine/threonine protein kinase (Akt)-dependent activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Interestingly, AS-IV attenuates PbAc-induced inhibition of neurite outgrowth and displayed potential antioxidant properties by inhibiting reactive oxygen species (ROS)...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315440/optimized-production-and-characterization-of-a-detergent-stable-protease-from-lysinibacillus-fusiformis-c250r
#13
REVIEW
Sondes Mechri, Mouna Kriaa, Mouna Ben Elhoul Berrouina, Maroua Omrane Benmrad, Nadia Zaraî Jaouadi, Hatem Rekik, Khelifa Bouacem, Amel Bouanane-Darenfed, Alif Chebbi, Sami Sayadi, Mohamed Chamkha, Samir Bejar, Bassem Jaouadi
In this study, we aimed to optimize the cultural and nutritional conditions for protease production by Lysinibacillus fusiformis strain C250R in submerged fermentation process using statistical methodology. The most significant factors (gruel, wheat bran, yeast extract, and FeSO4) were identified by Plackett-Burman design. Response surface methodology (RSM) was used to determine the optimum levels of the screened factors and their interaction. Under the optimized conditions, protease yield 3100U/mL was 4.5 folds higher than those obtained by the use of the initial conditions (680U/ml)...
March 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28315357/therapeutic-potential-of-krait-venom
#14
Antony Gomes, Partha Pratim Saha, Shamik Bhattacharya, Sourav Ghosh, Aparna Gomes
Kraits belong to Elapideae and are widely distributed in East and South-East Asian countries. Krait venom possesses neurotoxins, membrane toxins, cardiotoxins, three finger toxins, metalloproteinases, cholinesterases, L-amino acid oxidases and serine proteases. The therapeutic potential of krait venom in pathophysiological conditions such as microbial and parasitic infections, cancer, arthritis, inflammation and blood coagulation disorder is discussed in this review. More intensive new research ventures are required to establish the therapeutic potential of krait venom in complex and emerging diseases...
March 14, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28315351/-3-h-bmt-046091-a-potent-and-selective-radioligand-to-determine-aak1-distribution-and-target-engagement
#15
Justin V Louis, Yifeng Lu, Rick Pieschl, Yung Tian, Yang Hong, Kumaran Dandapani, Sreenivasulu Naidu, Reeba K Vikramadithyan, Carolyn Dzierba, Sarat Kumar Sarvasiddhi, Susheel J Nara, Joanne Bronson, John E Macor, Charlie Albright, Walter Kostich, Yu-Wen Li
Adaptor-associated kinase 1 (AAK1), a member of the Ark1/Prk1 family of serine/threonine kinases, plays a role in modulating clatherin coated endocytosis of specific surface receptors. We have demonstrated that AAK1 inhibitors are efficacious in rodent models of neuropathic pain (Kostich et al., 2016). Here we have characterized the binding properties and distribution pattern of the tritiated AAK1 radioligand, [(3)H]BMT-046091, in rodents and cynomolgus monkeys, and used the radioligand to measure the brain target occupancy following systemic administration of AAK1 inhibitors...
March 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28306533/ros-mediated-induction-of-apoptosis-by-benzoquinone-embelin-in-human-colon-adenocarcinoma-cells-ht-29
#16
Kodandaram Sumalatha, Mohan Gowda, Sreepriya Meenakshisundaram
Background Embelin is a benzoquinone reported to possess anticancer activity in several in vivo and in vitro models of carcinogenesis, especially hematopoietic and prostate malignancy. A detailed investigation on the influence of embelin on epithelial malignancy model system, especially colon adenocarcinoma, is lacking. The objective of the current study is to investigate the antiproliferative, antiinvasive and proapoptotic potential of embelin on colon adenocarcinoma cell line HT-29. Methods The effect of embelin (35 µg/mL for 24 h) on cell proliferation was assessed by Sulforhodamine B assay and bromodeoxyuridine incorporation test, antiinvasive effect by Boyden chamber assay and scratch assay...
March 17, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28306189/map4k4-is-a-novel-mapk-erk-pathway-regulator-required-for-lung-adenocarcinoma-maintenance
#17
Xuan Gao, Guangming Chen, Chenxi Gao, Dennis Han Zhang, Shih-Fan Kuan, Laura P Stabile, Guoxiang Liu, Jing Hu
About 76% of lung adenocarcinoma patients harbor activating mutations in the receptor tyrosine kinase (RTK)/RAS/RAF pathways, leading to aberrant activation of the MAPK pathways particularly the MAPK/ERK pathway. However, many lung adenocarcinomas lacking these genomic mutations also display significant MAPK pathway activation, suggesting that additional MAPK pathway alterations remain undetected. This study has identified serine/threonine kinase mitogen-activated protein 4 kinase 4 (MAP4K4) as a novel positive regulator of MAPK/ERK signaling in lung adenocarcinoma...
March 17, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28303635/incident-microalbuminuria-and-complement-factor-mannan-binding-lectin-associated-protein-19-in-people-with-newly-diagnosed-type-1-diabetes
#18
J A Ostergaard, S Thiel, I T Hoffmann-Petersen, P Hovind, H-H Parving, L Tarnow, P Rossing, T K Hansen
BACKGROUND: Evidence links the lectin pathway of complement activation to diabetic kidney disease. Upon carbohydrate-recognition by pattern-recognition molecules, e.g., mannan-binding lectin (MBL), the MBL-associated serine protease (MASP-2) is activated and initiates the complement cascade. The MASP2 gene encodes MASP-2 and the alternative splice product MBL-associated protein 19 (MAp19). Both MAp19 and MASP-2 circulate in complex with MBL. We tested the hypothesis that MAp19 and MASP-2 concentrations predict the risk of incident microalbuminuria...
March 16, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28303356/the-association-of-plasminogen-activator-inhibitor-type-1-pai-1-level-and-pai-1-4g-5g-gene-polymorphism-with-the-formation-and-the-grade-of-endometrial-cancer
#19
Malik Ejder Yıldırım, Savas Karakuş, Hande Küçük Kurtulgan, Hasan Kılıçgün, Serpil Erşan, Sevtap Bakır
Plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor (Serpine 1), and it inhibits both tissue plasminogen activator and urokinase plasminogen activator which are important in fibrinolysis. We aimed to find whether there is a possible association between PAI-1 level, PAI-1 4G/5G polymorphism, and endometrial cancer. PAI-1 levels in peripheral blood were determined in 82 patients with endometrial carcinoma and 76 female healthy controls using an enzyme-linked immunoassay (ELISA). Then, the genomic DNA was extracted and screened by reverse hybridization procedure (Strip assay) to detect PAI 1 4G/5G polymorphism...
March 16, 2017: Biochemical Genetics
https://www.readbyqxmd.com/read/28303123/trichoderma-asperellum-t42-and-pseudomonas-fluorescens-okc-enhances-resistance-of-pea-against-erysiphe-pisi-through-enhanced-ros-generation-and-lignifications
#20
Jai S Patel, Ravindra N Kharwar, Harikesh B Singh, Ram S Upadhyay, Birinchi K Sarma
Plant signaling mechanisms are not completely understood in plant-fungal biotrophic pathogen interactions. Further how such interactions are influenced by compatible rhizosphere microbes are also not well-studied. Therefore, we explored the pea-Erysiphe pisi (obligate biotroph) system to understand the interaction and applied compatible rhizospheric bio-agents Trichoderma asperellum (T42) and Pseudomonas fluorescens (OKC) singly or in combination to assess their influence on the host while under the pathogen challenge...
2017: Frontiers in Microbiology
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