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https://www.readbyqxmd.com/read/28346571/is-the-ergogenicity-of-caffeine-affected-by-increasing-age-the-direct-effect-of-a-physiological-concentration-of-caffeine-on-the-power-output-of-maximally-stimulated-edl-and-diaphragm-muscle-isolated-from-the-mouse
#1
J Tallis, R S James, V M Cox, M J Duncan
INTRODUCTION: Caffeine is a well-established performance enhancing nutritional supplement in a young healthy population, however far less is known about how its ergogenicity is affected by increasing age. A recent review has highlighted the value of studies examining the direct effect of caffeine on isolated skeletal muscle contractility, but the present work is the first to assess the direct effect of 70µM caffeine (physiological maximum) on the maximal power output of isolated mammalian muscle from an age range representing developmental to early ageing...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28346476/reduced-dosage-of-%C3%AE-catenin-provides-significant-rescue-of-cardiac-outflow-tract-anomalies-in-a-tbx1-conditional-null-mouse-model-of-22q11-2-deletion-syndrome
#2
Silvia E Racedo, Erica Hasten, Mingyan Lin, Gnanapackiam Sheela Devakanmalai, Tingwei Guo, Ertugrul M Ozbudak, Chen-Leng Cai, Deyou Zheng, Bernice E Morrow
The 22q11.2 deletion syndrome (22q11.2DS; velo-cardio-facial syndrome; DiGeorge syndrome) is a congenital anomaly disorder in which haploinsufficiency of TBX1, encoding a T-box transcription factor, is the major candidate for cardiac outflow tract (OFT) malformations. Inactivation of Tbx1 in the anterior heart field (AHF) mesoderm in the mouse results in premature expression of pro-differentiation genes and a persistent truncus arteriosus (PTA) in which septation does not form between the aorta and pulmonary trunk...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346428/autophagy-is-required-for-cell-survival-under-l-asparaginase-induced-metabolic-stress-in-acute-lymphoblastic-leukemia-cells
#3
H Takahashi, J Inoue, K Sakaguchi, M Takagi, S Mizutani, J Inazawa
L-asparaginase has been used for more than three decades in acute lymphoblastic leukemia (ALL) patients and remains an essential drug in the treatment of ALL. Poor response to L-asparaginase is associated with increased risk of therapeutic failure in ALL. However, both the metabolic perturbation and molecular context of L-asparaginase-treated ALL cells has not been fully elucidated. Here we identify that treatment with L-asparaginase results in metabolic shutdown via the reduction of both glycolysis and oxidative phosphorylation, accompanied by mitochondrial damage and activation of autophagy...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346135/polo-like-kinase-dependent-phosphorylation-of-the-synaptonemal-complex-protein-syp-4-regulates-double-strand-break-formation-through-a-negative-feedback-loop
#4
Saravanapriah Nadarajan, Talley J Lambert, Elisabeth Altendorfer, Jinmin Gao, Michael D Blower, Jennifer C Waters, Monica P Colaiácovo
The synaptonemal complex (SC) is an ultrastructurally conserved proteinaceous structure that holds homologous chromosomes together and is required for the stabilization of pairing interactions and the completion of crossover (CO) formation between homologs during meiosis I. Here, we identify a novel role for a central region component of the SC, SYP-4, in negatively regulating formation of recombination-initiating double-strand breaks (DSBs) via a feedback loop triggered by crossover designation in C. elegans...
March 27, 2017: ELife
https://www.readbyqxmd.com/read/28345958/macrophage-elastase-induces-trail-mediated-tumor-cell-death-through-its-carboxyterminal-domain
#5
Nadine Dandachi, Neil J Kelly, John P Wood, Christine L Burton, Josiah E Radder, Adriana S Leme, Alyssa D Gregory, Steven D Shapiro
RATIONALE: Macrophage elastase (MMP12) is a potent protease that contributes to the lung destruction that accompanies cigarette smoking while it simultaneously inhibits lung tumor angiogenesis and metastasis by catalyzing the formation of anti-angiogenic peptides. Recent studies have revealed novel non-proteolytic functions of MMP12, including antimicrobial activity through a peptide within its C-terminal domain (CTD). OBJECTIVES: Our objective was to determine whether the MMP12 CTD contributes to its anti-tumor activity in lung cancer...
March 27, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28345916/molecular-mechanism-of-nucleotide-dependent-allosteric-regulation-in-amp-activated-protein-kinase
#6
Navjeet Ahalawat, Rajesh Kumar Murarka
The AMP-activated protein kinase (AMPK), a central enzyme in the regulation of energy homeostasis, is an important drug target for type 2 diabetes, obesity and cancer. Binding of adenosine nucleotides to the regulatory γ-subunit tightly regulates the activity of this enzyme. Though recent crystal structures of AMPK have provided important insights into the allosteric activation of AMPK, molecular details of the regulatory mechanism of AMPK activation is still elusive. Here, we have performed extensive all-atom molecular dynamics (MD) simulations and shown that the kinase domain (KD) and γ-subunit comes closer resulting in a more compact heterotrimeric AMPK complex in AMP-bound state compared to the ATP-bound state...
March 27, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28345895/asymmetric-anchoring-is-required-for-efficient-%C3%AE-loop-opening-and-closing-in-cytosolic-phosphoenolpyruvate-carboxykinase
#7
Danica Cui, Aron Broom, Matthew J Mcleod, Elizabeth M Meiering, Todd Holyoak
Mobile Ω-loops play essential roles in the function of many enzymes. Here we investigated the importance of a residue lying outside of the mobile Ω-loop element in the catalytic function of an H477R variant of cPEPCK using crystallographic, kinetic, and computational analysis. The crystallographic data suggest that efficient transitioning of the Ω-loop to the closed conformation requires stabilization of the N-terminus of the loop through contacts between R461 and E588. In contrast, the C-terminal end of the Ω-loop undergoes changing interactions with the enzyme body through contacts between H477 at the C-terminus of the loop and E591 located on the enzyme body...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28345892/a-silver-specific-dnazyme-with-a-new-silver-aptamer-and-salt-promoted-activity
#8
Runjhun Saran, Kimberly Kleinke, Wenhu Zhou, Tianmeng Yu, Juewen Liu
Most RNA-cleaving DNAzymes require a metal ion to interact with the scissile phosphate for activity. Therefore, few unmodified DNAzymes work with thiophilic metals due to their low affinity to phosphate. Recently, an Ag+-specific Ag10c DNAzyme was reported via in vitro selection. Herein, the Ag10c is characterized to rationalize the role of the strongly thiophilic Ag+. Systematic mutation studies indicate that the Ag10c is a highly conserved DNAzyme and its Ag+ binding is unrelated to C-Ag+-C interaction. Its activity is enhanced with Na+ concentrations of buffer...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28345674/skeletal-muscle-pump-drives-control-of-cardiovascular-and-postural-systems
#9
Ajay K Verma, Amanmeet Garg, Da Xu, Michelle Bruner, Reza Fazel-Rezai, Andrew P Blaber, Kouhyar Tavakolian
The causal interaction between cardio-postural-musculoskeletal systems is critical in maintaining postural stability under orthostatic challenge. The absence or reduction of such interactions could lead to fainting and falls often experienced by elderly individuals. The causal relationship between systolic blood pressure (SBP), calf electromyography (EMG), and resultant center of pressure (COPr) can quantify the behavior of cardio-postural control loop. Convergent cross mapping (CCM) is a non-linear approach to establish causality, thus, expected to decipher nonlinear causal cardio-postural-musculoskeletal interactions...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345661/stepwise-analysis-of-mir9-loci-identifies-mir-9-5p-to-be-involved-in-oestrogen-regulated-pathways-in-breast-cancer-patients
#10
Raffaela Barbano, Barbara Pasculli, Michelina Rendina, Andrea Fontana, Caterina Fusilli, Massimiliano Copetti, Stefano Castellana, Vanna Maria Valori, Maria Morritti, Paolo Graziano, Ciuffreda Luigi, Michelina Coco, Francesco Picardo, Tommaso Mazza, Ella Evron, Roberto Murgo, Evaristo Maiello, Manel Esteller, Vito Michele Fazio, Paola Parrella
miR-9 was initially identified as an epigenetically regulated miRNA in tumours, but inconsistent findings have been reported so far. We analysed the expression of miR-9-5p, miR-9-3p, pri-miRs and MIR9 promoters methylation status in 131 breast cancer cases and 12 normal breast tissues (NBTs). The expression of both mature miRs was increased in tumours as compared to NBTs (P < 0.001) and negatively correlated with ER protein expression (P = 0.005 and P = 0.003, for miR-9-3p and miR-9-5p respectively)...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345627/heterologous-protein-dna-interactions-lead-to-biased-allelic-expression-of-circadian-clock-genes-in-interspecific-hybrids
#11
Danny W-K Ng, Helen H Y Chen, Z Jeffrey Chen
Genomic interactions in allopolyploids create expression variation of homoeologous alleles through protein-protein and protein-DNA interactions. However, the molecular basis for this is largely unknown. Here we investigated the protein-protein and protein-DNA interactions among homoeologous transcription factors in the circadian-clock feedback loop, consisting of CCA1 HIKING EXPEDITION (CHE), CIRCADIAN CLOCK ASSOCIATED1 (CCA1), and TIMING OF CAB EXPRESSION1 (TOC1), plus the interaction with a chromatin factor, HISTONE DEACETYLASE1 (HD1)...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345596/crystal-structure-of-zika-virus-ns5-rna-dependent-rna-polymerase
#12
Andre S Godoy, Gustavo M A Lima, Ketllyn I Z Oliveira, Naiara U Torres, Fernando V Maluf, Rafael V C Guido, Glaucius Oliva
The current Zika virus (ZIKV) outbreak became a global health threat of complex epidemiology and devastating neurological impacts, therefore requiring urgent efforts towards the development of novel efficacious and safe antiviral drugs. Due to its central role in RNA viral replication, the non-structural protein 5 (NS5) RNA-dependent RNA-polymerase (RdRp) is a prime target for drug discovery. Here we describe the crystal structure of the recombinant ZIKV NS5 RdRp domain at 1.9 Å resolution as a platform for structure-based drug design strategy...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345467/mitochondrial-dna-alteration-in-primary-and-metastatic-colorectal-cancer-different-frequency-and-association-with-selected-clinicopathological-and-molecular-markers
#13
Britta Kleist, Thuja Meurer, Micaela Poetsch
This study attempts to determine whether primary tumor tissue could reliably represent metastatic colorectal cancer in therapy-guiding analysis of mitochondrial microsatellite instability. Therefore, we investigated the concordance of microsatellite instability in D310, D514, and D16184 (mitochondrial DNA displacement loop), and its association with selected clinical categories and KRAS/NRAS/BRAF/PIK3CA/TP53 mutation status between primary and metastatic colorectal cancer tissue from 119 patients. Displacement loop microsatellite instability was significantly more frequently seen in lymph node metastases (53...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345298/effects-of-t-loop-modification-on-the-pii-signaling-protein-structure-of-uridylylated-escherichia-coli-glnb-bound-to-atp
#14
Carles Palanca, Vicente Rubio
To adapt to environments with variable nitrogen sources and richness, the widely distributed homotrimeric PII signaling proteins bind their allosteric effectors ADP/ATP/2-oxoglutarate, and experience nitrogen-sensitive uridylylation of their flexible T-loops at Tyr51, regulating their interactions with effector proteins. To clarify whether uridylylation triggers a given T-loop conformation, we determined the crystal structure of the classical paradigm of PII protein, Escherichia coli GlnB (EcGlnB), in fully uridylylated form (EcGlnB-UMP3 )...
March 26, 2017: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/28345114/peripheral-endothelial-function-after-arterial-switch-operation-for-d-looped-transposition-of-the-great-arteries
#15
Heather Y Sun, Katie Jo Stauffer, Susan E Nourse, Chau Vu, Elif Seda Selamet Tierney
Coronary artery re-implantation during arterial switch operation in patients with D-looped transposition of the great arteries (D-TGA) can alter coronary arterial flow and increase shear stress, leading to local endothelial dysfunction, although prior studies have conflicting results. Endothelial pulse amplitude testing can predict coronary endothelial dysfunction by peripheral arterial testing. This study tested if, compared to healthy controls, patients with D-TGA after arterial switch operation had peripheral endothelial dysfunction...
March 27, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28345030/wearable-disposable-sweat-based-glucose-monitoring-device-with-multistage-transdermal-drug-delivery-module
#16
Hyunjae Lee, Changyeong Song, Yong Seok Hong, Min Sung Kim, Hye Rim Cho, Taegyu Kang, Kwangsoo Shin, Seung Hong Choi, Taeghwan Hyeon, Dae-Hyeong Kim
Electrochemical analysis of sweat using soft bioelectronics on human skin provides a new route for noninvasive glucose monitoring without painful blood collection. However, sweat-based glucose sensing still faces many challenges, such as difficulty in sweat collection, activity variation of glucose oxidase due to lactic acid secretion and ambient temperature changes, and delamination of the enzyme when exposed to mechanical friction and skin deformation. Precise point-of-care therapy in response to the measured glucose levels is still very challenging...
March 2017: Science Advances
https://www.readbyqxmd.com/read/28345008/insights-into-the-mechanism-of-membrane-pyrophosphatases-by-combining-experiment-and-computer-simulation
#17
Nita R Shah, Craig Wilkinson, Steven P D Harborne, Ainoleena Turku, Kun-Mou Li, Yuh-Ju Sun, Sarah Harris, Adrian Goldman
Membrane-integral pyrophosphatases (mPPases) couple the hydrolysis of pyrophosphate (PPi) to the pumping of Na(+), H(+), or both these ions across a membrane. Recently solved structures of the Na(+)-pumping Thermotoga maritima mPPase (TmPPase) and H(+)-pumping Vigna radiata mPPase revealed the basis of ion selectivity between these enzymes and provided evidence for the mechanisms of substrate hydrolysis and ion-pumping. Our atomistic molecular dynamics (MD) simulations of TmPPase demonstrate that loop 5-6 is mobile in the absence of the substrate or substrate-analogue bound to the active site, explaining the lack of electron density for this loop in resting state structures...
May 2017: Structural Dynamics (Melville, N.Y.)
https://www.readbyqxmd.com/read/28344962/efficacy-of-loop-electrosurgical-excision-procedure-with-cold-coagulation-for-treating-cervical-intraepithelial-neoplasia-a-two-center-cohort-study
#18
Hee Seung Kim, Jeong Eun Kwon, Jeong Ha Kim, Anna Kim, Na Ra Lee, Miseon Kim, Maria Lee, Dong Hoon Suh, Yong Beom Kim
OBJECTIVE: To evaluate the efficacy of loop electrosurgical excision procedure (LEEP) combined with cold coagulation for treating cervical intraepithelial neoplasia (CIN). METHODS: We reviewed clinic-pathologic data of 498 patients treated with LEEP alone (n=354), and LEEP combined with cold coagulation (n=144) between January 2000 and December 2011. After LEEP, we followed up all patients by using Papanicolaou smear and human papillomavirus (HPV) test, and evaluated abnormal cervical cytology-free interval and high-risk HPV infection-free interval...
March 2017: Obstetrics & Gynecology Science
https://www.readbyqxmd.com/read/28344951/a-case-of-littr%C3%A3-s-hernia-at-zinder-national-hospital-zinder-niger
#19
I Amadou Magagi, H Adamou, O Habou
The presence of a Meckel's diverticulum in a hernia sac is known as Littré's hernia. We report a case of Littré's hernia in an 18-year old young man because of the uncommon condition. An 18-year old young patient was admitted to the Emergency Surgical Department of Zinder National Hospital, Zinder, Niger with a painful inguinoscrotal swelling of three days duration. The diagnosis of strangulated right inguinoscrotal hernia was made. At surgery, a Meckel's diverticulum was found at the antimesenteric border of the ileum in the hernia sac, the bowel loop was not viable...
April 2016: Journal of the West African College of Surgeons
https://www.readbyqxmd.com/read/28344879/prostaglandin-e2-mediated-adenosinergic-effects-on-cd14-cells-self-amplifying-immunosuppression-in-cancer
#20
Saly Al-Taei, Josephine Salimu, Lisa K Spary, Aled Clayton, Jason F Lester, Zsuzsanna Tabi
CD39 and CD73 are surface-expressed ectonucleotidases that hydrolyze ATP in a highly regulated, serial manner into ADP, AMP and adenosine. The end product, adenosine, has both tumor-promoting and immunosuppressive effects. The aim of this study was to determine CD73 expression on immune cells in pleural effusion (PE) in order to have a better understanding of the immune environment in mesothelioma. PE- or blood-derived CD14(+) cells of mesothelioma patients and healthy donors were analyzed by flow cytometry for the expression of CD39 and CD73...
2017: Oncoimmunology
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