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https://www.readbyqxmd.com/read/28340340/selective-chemical-inhibition-of-pgc-1%C3%AE-gluconeogenic-activity-ameliorates-type-2-diabetes
#1
Kfir Sharabi, Hua Lin, Clint D J Tavares, John E Dominy, Joao Paulo Camporez, Rachel J Perry, Roger Schilling, Amy K Rines, Jaemin Lee, Marc Hickey, Melissa Bennion, Michelle Palmer, Partha P Nag, Joshua A Bittker, José Perez, Mark P Jedrychowski, Umut Ozcan, Steve P Gygi, Theodore M Kamenecka, Gerald I Shulman, Stuart L Schreiber, Patrick R Griffin, Pere Puigserver
Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28339997/straight-run-vs-sex-separate-rearing-for-2-broiler-genetic-lines-part-1-live-production-parameters-carcass-yield-and-feeding-behavior
#2
M J Da Costa, S Zaragoza-Santacruz, T J Frost, J Halley, G M Pesti
The objective of this experiment was to evaluate the effects of raising broilers under sex separate and straight-run conditions for 2 broiler strains. Day-old Ross 308 and Ross 708 chicks (n = 1,344) were separated by sex and placed in 48 pens according to the rearing type: sex separate (28 males or 28 females) or straight-run (14 males + 14 females). There were 3 dietary phases: starter (zero to 17 d), grower (17 to 32 d), and finisher (32 to 48 d). Birds' individual BW and feed intakes were measured at 12, 17, 25, 32, 42, and 48 d to evaluate performance...
March 4, 2017: Poultry Science
https://www.readbyqxmd.com/read/28339948/effects-of-dietary-coarsely-ground-corn-and-3-bedding-floor-types-on-broiler-live-performance-litter-characteristics-gizzard-and-proventriculus-weight-and-nutrient-digestibility
#3
Y Xu, Y M Lin, C R Stark, P R Ferket, C M Williams, J Brake
The effects of zero or 50% dietary coarsely ground corn (CC) in pelleted and screened grower and finisher diets on broilers reared on 3 bedding floor types (plastic net [NET], new pine wood shavings litter [NEW], or old pine wood shavings litter [OLD]) on broiler live performance, litter characteristics, gizzard and proventriculus weight, and apparent ileal digestibility (AID) were studied in a 2 × 3 factorial arrangement of treatments. Fine corn was produced with a hammermill (271 μm) and CC with a roller mill (1145 μm)...
March 2, 2017: Poultry Science
https://www.readbyqxmd.com/read/28339876/straight-run-vs-sex-separate-rearing-for-two-broiler-genetic-lines-part-2-economic-analysis-and-processing-advantages
#4
M J Da Costa, G Colson, T J Frost, J Halley, G M Pesti
The objective of this analysis was to evaluate the effects of raising broilers under sex separate and straight-run conditions for 2 broiler genetic lines. One-day-old Ross 308 and Ross 708 chicks (n = 1,344) were sex separated and placed in 48 pens according to rearing type: sex separate (28 males or 28 females) or straight-run (14 males + 14 females). There were 3 dietary phases: starter (zero to 17 d), grower (17 to 32 d), and finisher (32 to 48 d). Bird individual BW and group feed intakes were measured at 12, 17, 25, 32, 42, and 48 d to evaluate performance...
February 23, 2017: Poultry Science
https://www.readbyqxmd.com/read/28339623/the-molecular-and-clinical-epidemiology-of-extended-spectrum-cephalosporin-and-carbapenem-resistant-enterobacteriaceae-at-4-us-pediatric-hospitals
#5
Danielle M Zerr, Scott J Weissman, Chuan Zhou, Matthew P Kronman, Amanda L Adler, Jessica E Berry, Jaipreet Rayar, Jeff Myers, Wren L Haaland, Carey-Ann D Burnham, Alexis Elward, Jason Newland, Rangaraj Selvarangan, Kaede V Sullivan, Theoklis Zaoutis, Xuan Qin
Objective.: In this report, we aim to describe the epidemiology of extended-spectrum cephalosporin-resistant (ESC-R) and carbapenem-resistant (CR) Enterobacteriaceae infections in children. Methods.: ESC-R and CR Enterobacteriaceae isolates from normally sterile sites of patients aged <22 years from 4 freestanding pediatric medical centers were collected along with the associated clinical data. Results.: The overall frequencies of ESC-R and CR isolates according to hospital over the 4-year study period ranged from 0...
January 19, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28339275/ultrafast-photoinduced-electric-polarization-switching-in-a-hydrogen-bonded-ferroelectric-crystal
#6
K Iwano, Y Shimoi, T Miyamoto, D Hata, M Sotome, N Kida, S Horiuchi, H Okamoto
Croconic acid crystals show proton displacive-type ferroelectricity with a large spontaneous polarization reaching 20  μC/cm^{2}, which originates from the strong coupling of proton and π-electron degrees of freedom. Such a coupling makes us expect a large polarization change by photoirradiations. Optical-pump second-harmonic-generation-probe experiments reveal that a photoexcited croconic-acid crystal loses the ferroelectricity substantially with a maximum quantum efficiency of more than 30 molecules per one absorbed photon...
March 10, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/28334989/impaired-fetal-muscle-development-and-jak-stat-activation-mark-disease-onset-and-progression-in-a-mouse-model-for-merosin-deficient-congenital-muscular-dystrophy
#7
Andreia M Nunes, Ryan D Wuebbles, Apurva Sarathy, Tatiana M Fontelonga, Marianne Deries, Dean J Burkin, Sólveig Thorsteinsdóttir
Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a dramatic neuromuscular disease in which crippling muscle weakness is evident from birth. Here we use the dyW mouse model for human MDC1A to trace the onset of the disease during development in utero. We find that myotomal and primary myogenesis proceed normally in homozygous dyW-/-embryos. Fetal dyW-/-muscles display the same number of myofibers as wildtype muscles, but by E18.5 dyW-/-muscles are significantly smaller and muscle size is not recovered post-natally...
March 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334793/compound-heterozygous-mutations-in-the-gene-pigp-are-associated-with-early-infantile-epileptic-encephalopathy
#8
Devon L Johnstone, Thi Tuyet-Mai Nguyen, Yoshiko Murakami, Kristin D Kernohan, Martine Tétreault, Claire Goldsmith, Asif Doja, Justin D Wagner, Lijia Huang, Taila Hartley, Anik St-Denis, Françoise le Deist, Jacek Majewski, Dennis E Bulman, Taroh Kinoshita, David A Dyment, Kym M Boycott, Philippe M Campeau
There are over 150 known human proteins which are tethered to the cell surface via glycosylphosphatidylinositol (GPI) anchors. These proteins play a variety of important roles in development, and particularly in neurogenesis. Not surprisingly, mutations in the GPI anchor biosynthesis and remodeling pathway cause a number of developmental disorders. This group of conditions has been termed inherited GPI deficiencies (IGDs), a subgroup of congenital disorders of glycosylation; they present with variable phenotypes, often including seizures, hypotonia and intellectual disability...
March 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334439/a-phase-2-trial-of-dasatinib-in-patients-with-locally-advanced-or-stage-iv-mucosal-acral-or-vulvovaginal-melanoma-a-trial-of-the-ecog-acrin-cancer-research-group-e2607
#9
Kevin Kalinsky, Sandra Lee, Krista M Rubin, Donald P Lawrence, Anthony J Iafrarte, Darell R Borger, Kim A Margolin, Mario M Leitao, Ahmad A Tarhini, Henry B Koon, Andrew L Pecora, Anthony J Jaslowski, Gary I Cohen, Timothy M Kuzel, Christopher D Lao, John M Kirkwood
BACKGROUND: KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Dasatinib has superior preclinical activity in comparison with other tyrosine kinase inhibitors against cells with the most common KIT mutation, exon 11(L576P) . The ECOG-ACRIN E2607 trial assessed dasatinib in patients with these melanoma subtypes. METHODS: Patients received 70 mg of oral dasatinib twice daily...
March 23, 2017: Cancer
https://www.readbyqxmd.com/read/28333903/-evaluation-of-oro-cecal-transit-time-in-patients-with-irritable-bowel-syndrome-with-cereal-products-intolerance
#10
Aleksandra Błońska, Paulina Konrad, Jan Chojnacki, Cezary Chojnacki
The main symptoms of irritable bowel syndrome (IBS) include abnormal frequency of bowel movements. On this basis, three main clinical types of the disease have been distinguished, i.e.: constipation (IBSC), diarrhea (IBS-D) and mixed-type (IBS-M) in accordance with the Rome III criteria. These disorders mainly affect the colon, but symptoms related to upper gastrointestinal tract are also often observed. AIM: The aim of the study was to assess the oro-caecal transit time in patients with irritable bowel syndrome with IgG-dependent hypersensitivity to cereal products...
March 21, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28333319/wck-4234-a-novel-diazabicyclooctane-potentiating-carbapenems-against-enterobacteriaceae-pseudomonas-and-acinetobacter-with-class-a-c-and-d-%C3%AE-lactamases
#11
Shazad Mushtaq, Anna Vickers, Neil Woodford, David M Livermore
Background: Several diazabicyclooctanes (DBOs) are under development as inhibitors of class A and C β-lactamases. Inhibition of OXA (class D) carbapenemases is variable, with those of Acinetobacter spp. remaining notably resistant. We describe a novel DBO, WCK 4234 (Wockhardt), with distinctive activity against OXA carbapenemases. Methods: MICs of imipenem and meropenem were determined by CLSI agar dilution with WCK 4234 added at 4 or 8 mg/L. Test organisms were clinical Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa with carbapenemases or carbapenem resistance via porin loss plus AmpC or ESBL activity...
February 16, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28332036/the-committed-intimate-partnerships-of-incarcerated-african-american-men-implications-for-sexual-hiv-transmission-risk-and-prevention-opportunities
#12
Maria R Khan, Nabila El-Bassel, Carol E Golin, Joy D Scheidell, Adaora A Adimora, Ashley M Coatsworth, Hui Hu, Selena Judon-Monk, Katie P Medina, David A Wohl
Incarceration is thought to influence HIV transmission by disrupting partnerships that provide support and protect against sex risk-taking. Current correctional facility-based family-strengthening programs focus on marital partnerships, a minority of inmates' partnerships. Research on the sex partnerships of incarcerated African-American men and the types of partnerships most likely to protect against HIV-related sex risk is limited. Improved understanding can inform expansion of correctional facility-based family-strengthening programs to a greater proportion of protective partnerships and HIV risk reduction programs to partnerships vulnerable to sex risk...
March 22, 2017: Archives of Sexual Behavior
https://www.readbyqxmd.com/read/28331055/reticular-dysgenesis-international-survey-on-clinical-presentation-transplantation-and-outcome
#13
Manfred Hoenig, Chantal Lagresle-Peyrou, Ulrich Pannicke, Luigi D Notarangelo, Fulvio Porta, Andrew R Gennery, Mary Slatter, Morton J Cowan, Polina Stepensky, Hamoud Al-Mousa, Daifulah Al-Zahrani, Sung-Yun Pai, Waleed Al Herz, Hubert B Gaspar, Paul Veys, Koichi Oshima, Kohsuke Imai, Hiromasa Yabe, Lenora M Noroski, Nico M Wulffraat, Karl-Walter Sykora, Pere Soler-Palacin, Hideki Muramatsu, Mariam Al Hilali, Despina Moshous, Klaus-Michael Debatin, Catharina Schuetz, Eva-Maria Jacobsen, Ansgar S Schulz, Klaus Schwarz, Alain Fischer, Wilhelm Friedrich, Marina Cavazzana
Reticular Dysgenesis (RD) is a rare congenital disorder defined clinically by the combination of severe combined immunodeficiency (SCID), agranulocytosis and sensorineural deafness. Mutations in the gene encoding Adenylate Kinase 2 (AK2) were identified to cause the disorder. Hematopoietic stem cell transplantation (HSCT) is the only option to cure this otherwise fatal disease. Retrospective data on clinical presentation, genetics and outcome of HSCT were collected from centers in Europe, Asia and North America for a total of 32 patients born between 1982 and 2011...
March 22, 2017: Blood
https://www.readbyqxmd.com/read/28330103/profiling-and-production-of-hemicellulases-by-thermophilic-fungus-malbranchea-flava-and-the-role-of-xylanases-in-improved-bioconversion-of-pretreated-lignocellulosics-to-ethanol
#14
Manju Sharma, Chhavi Mahajan, Manpreet S Bhatti, Bhupinder Singh Chadha
This study reports thermophilic fungus Malbranchea flava as a potent source of xylanase and xylan-debranching accessory enzymes. M. flava produced high levels of xylanase on sorghum straw containing solidified culture medium. The optimization of culture conditions for production of hemicellulases was carried out using one factor at a time approach and Box-Behnken design of experiments with casein (%), inoculum age (h) and inoculum level (ml) as process variables and xylanase, β-xylosidase, acetyl esterases and arabinofuranosidase as response variables...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329892/ocular-toxoplasmosis-therapy-related-adverse-drug-reactions-and-their-management
#15
M Helfenstein, S Zweifel, D Barthelmes, F Meier, J Fehr, C Böni
Background There are different treatment options for ocular toxoplasmosis (OT). "Classic" therapy consists of pyrimethamine, sulfadiazine and folinic acid combined with systemic steroids and is still widely used. However, potentially severe side effects of this therapy have been reported. The aim of this retrospective study was to evaluate the incidence and types of adverse drug reactions in patients treated for OT. Clinical management of each adverse drug reaction was assessed. Patients and Methods In this retrospective analysis, we reviewed data of patients with OT, who were consecutively examined between December 2011 and December 2015 at the Department of Ophthalmology, University Hospital Zurich...
March 22, 2017: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/28329730/synthesis-of-novel-quinoline-based-4-5-dihydro-1h-pyrazoles-as-potential-anticancer-antifungal-antibacterial-and-antiprotozoal-agents
#16
Jonathan Ramírez-Prada, Sara M Robledo, Iván D Vélez, María Del Pilar Crespo, Jairo Quiroga, Rodrigo Abonia, Alba Montoya, Laura Svetaz, Susana Zacchino, Braulio Insuasty
A new series of N-substituted 2-pyrazolines 9a-f, 10a-f, 11a-f, 12a-f and 13a-f were obtained from the cyclocondensation reaction of [(7-chloroquinolin-4-yl)amino]chalcones 8a-f with hydrazine hydrate and its derivatives. Fourteen of the synthesized compounds including the starting chalcones were selected by US National Cancer Institute (NCI) for testing their anticancer activity against 60 different human cancer cell lines, with the most important GI50 values ranging from 0.28 to 11.7 μM (0.13-6.05 μg/mL) and LC50 values ranging from 2...
March 16, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28329458/type-iv-total-anomalous-pulmonary-venous-connection
#17
James D St Louis, Elizabeth M Turk, Jeffrey P Jacobs, James E O'Brien
BACKGROUND: Mortality associated with correction of type IV total anomalous pulmonary venous connection (TAPVC) is generally reported in combination with other anatomic types. The objective of this study is to review surgical outcomes associated with the repair of type IV TAPVC by analyzing a multi-institutional cohort specific for this group. We also analyze patient-specific variables that may contribute to poor operative outcomes. METHODS: A retrospective review of the Pediatric Cardiac Care Consortium (PCCC) registry identified patients who underwent repair of type IV TAPVC between 1982 and 2007...
March 2017: World Journal for Pediatric & Congenital Heart Surgery
https://www.readbyqxmd.com/read/28328347/prevention-of-hereditary-angioedema-attacks-with-a-subcutaneous-c1-inhibitor
#18
Hilary Longhurst, Marco Cicardi, Timothy Craig, Konrad Bork, Clive Grattan, James Baker, Huamin H Li, Avner Reshef, James Bonner, Jonathan A Bernstein, John Anderson, William R Lumry, Henriette Farkas, Constance H Katelaris, Gordon L Sussman, Joshua Jacobs, Marc Riedl, Michael E Manning, Jacques Hebert, Paul K Keith, Shmuel Kivity, Sergio Neri, Donald S Levy, Maria L Baeza, Robert Nathan, Lawrence B Schwartz, Teresa Caballero, William Yang, Ioana Crisan, María D Hernandez, Iftikhar Hussain, Michael Tarzi, Bruce Ritchie, Pavlina Králíčková, Mar Guilarte, Syed M Rehman, Aleena Banerji, Richard G Gower, Debra Bensen-Kennedy, Jonathan Edelman, Henrike Feuersenger, John-Philip Lawo, Thomas Machnig, Dipti Pawaskar, Ingo Pragst, Bruce L Zuraw
Background Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks. Methods We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening...
March 23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28327932/integrated-safety-analysis-of-rolapitant-with-coadministered-drugs-from-phase-ii-iii-trials-an-assessment-of-cyp2d6-or-bcrp-inhibition-by-rolapitant
#19
S Barbour, T Smit, X Wang, D Powers, S Arora, V Kansra, M Aapro, J Herrstedt
Background: Rolapitant, a long-acting neurokinin (NK) 1 receptor antagonist (RA), has demonstrated efficacy in prevention of chemotherapy-induced nausea and vomiting in patients administered moderately or highly emetogenic chemotherapy. Unlike other NK 1 RAs, rolapitant does not inhibit or induce cytochrome P450 (CYP) 3A4, but it does inhibit CYP2D6 and breast cancer resistance protein (BCRP). To analyze potential drug-drug interactions between rolapitant and concomitant medications, this integrated safety analysis of four double-blind, randomized phase II or III studies of rolapitant examined adverse events by use versus non-use of drug substrates of CYP2D6 or BCRP...
February 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327356/type-2-inositol-trisphosphate-receptor-gene-expression-in-hepatocytes-is-regulated-by-cyclic-amp
#20
Emma Kruglov, M Ananthanarayanan, Pedro Sousa, Jittima Weerachayaphorn, Mateus T Guerra, Michael H Nathanson
The type 2 inositol 1,4,5-trisphosphate receptor (IP3R2) is the principal intracellular Ca(2+) release channel in hepatocytes, and so is important for bile secretion and other functions. IP3R2 activity is regulated in part by post-translational modifications but little is known about transcriptional regulation of its expression. We found that both IP3R2 mRNA and protein levels in liver were increased during fasting. Treatment of hepatocytes with forskolin or 8-CPT-cAMP also increased IP3R2, and this was reduced by actinomycin D...
March 18, 2017: Biochemical and Biophysical Research Communications
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