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https://www.readbyqxmd.com/read/28432813/targeting-on-poly-adp-ribose-polymerase-activity-with-dna-damaging-hybrid-lactam-steroid-alkylators-in-wild-type-and-brca1-mutated-ovarian-cancer-cells
#1
Dimitrios T Trafalis, Aikaterini Polonifi, Panayiotis Dalezis, Nikolaos Nikoleousakos, Sotirios Katsamakas, Vassiliki Sarli
Conjugated lactam-steroid alkylators (LSA), have been shown to exhibit superior activity at controlling cancer models and overlap drug resistance to conventional chemotherapy. Hybrid LSAs combine two active compounds in a single molecule and incorporate modified steroids bearing lactam moiety in one or more steroid rings functioning as vectors for cytotoxic agents. We first describe a novel class of LSAs that generate excellent anticancer activity against UWB1.289 and UWB1.289+BRCA1 human ovarian cancer cell lines...
April 22, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28432777/preparative-isoelectric-focusing-in-a-cellulose-based-separation-medium
#2
Jiří Šalplachta, Marie Horká, Karel Šlais
An improved preparative method based on isoelectric focusing of analytes in a cellulose-based separation medium is described in this study. Cellulose is suspended in an aqueous solution of simple buffers, ethylene glycol, glycerol, nonionic surfactant, and colored pI markers. Water partially evaporates during focusing run and the separation takes place in an in-situ generated layer of cellulose, which has a gel-like appearance at the end of analysis. Final positions of analytes are indicated by the positions of zones of focused pI markers...
April 22, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28432654/laser-desorption-ionization-mass-spectrometric-imaging-of-endogenous-lipids-from-rat-brain-tissue-implanted-with-silver-nanoparticles
#3
Ludovic Muller, Kathrine Baldwin, Damon C Barbacci, Shelley N Jackson, Aurélie Roux, Carey D Balaban, Bruce E Brinson, Michael I McCully, Ernest K Lewis, J Albert Schultz, Amina S Woods
Mass spectrometry imaging (MSI) of tissue implanted with silver nanoparticulate (AgNP) matrix generates reproducible imaging of lipids in rodent models of disease and injury. Gas-phase production and acceleration of size-selected 8 nm AgNP is followed by controlled ion beam rastering and soft landing implantation of 500 eV AgNP into tissue. Focused 337 nm laser desorption produces high quality images for most lipid classes in rat brain tissue (in positive mode: galactoceramides, diacylglycerols, ceramides, phosphatidylcholines, cholesteryl ester, and cholesterol, and in negative ion mode: phosphatidylethanolamides, sulfatides, phosphatidylinositol, and sphingomyelins)...
April 21, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28432489/design-development-and-clinical-validation-of-computer-aided-surgical-simulation-system-for-streamlined-orthognathic-surgical-planning
#4
REVIEW
Peng Yuan, Huaming Mai, Jianfu Li, Dennis Chun-Yu Ho, Yingying Lai, Siting Liu, Daeseung Kim, Zixiang Xiong, David M Alfi, John F Teichgraeber, Jaime Gateno, James J Xia
PURPOSE: There are many proven problems associated with traditional surgical planning methods for orthognathic surgery. To address these problems, we developed a computer-aided surgical simulation (CASS) system, the AnatomicAligner, to plan orthognathic surgery following our streamlined clinical protocol. METHODS: The system includes six modules: image segmentation and three-dimensional (3D) reconstruction, registration and reorientation of models to neutral head posture, 3D cephalometric analysis, virtual osteotomy, surgical simulation, and surgical splint generation...
April 21, 2017: International Journal of Computer Assisted Radiology and Surgery
https://www.readbyqxmd.com/read/28432455/dual-activation-of-toll-like-receptors-7-and-9-impairs-the-efficacy-of-antitumor-vaccines-in-murine-models-of-metastatic-breast-cancer
#5
Mariela A Moreno Ayala, María Florencia Gottardo, María Soledad Gori, Alejandro Javier Nicola Candia, Carla Caruso, Andrea De Laurentiis, Mercedes Imsen, Slobodanka Klein, Elisa Bal de Kier Joffé, Gabriela Salamone, Maria G Castro, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28432448/resistance-to-radial-expansion-limits-muscle-strain-and-work
#6
E Azizi, A R Deslauriers, N C Holt, C E Eaton
The collagenous extracellular matrix (ECM) of skeletal muscle functions to transmit force, protect sensitive structures, and generate passive tension to resist stretch. The mechanical properties of the ECM change with age, atrophy, and neuromuscular pathologies, resulting in an increase in the relative amount of collagen and an increase in stiffness. Although numerous studies have focused on the effect of muscle fibrosis on passive muscle stiffness, few have examined how these structural changes may compromise contractile performance...
April 21, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28432330/enhanced-response-of-metformin-towards-the-cancer-cells-due-to-synergism-with-multi-walled-carbon-nanotubes-in-photothermal-therapy
#7
Sweejiang Yoo, Jin Hou, Wenhui Yi, Yingchun Li, Weiping Chen, Lingjie Meng, Jinhai Si, Xun Hou
Converging evidence from laboratory models pointed that the widely used antidiabetic drug metformin has direct effects on cancer cells. Thus far, relatively little attention has been addressed to the drug exposures used experimentally relative to those achievable clinically. Here, we demonstrated that metformin loaded on carbon nanotubes under near-infrared (NIR) irradiation led to the remarkably enhancement in response towards cancer cells. The dose of metformin has reduced to only 1/280 of typical doses in monotherapy (35: 10 000-30 000 µM) where the realization of metformin in conventional antidiabetic doses for cancer therapies becomes possible...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432257/excess-diffuse-light-absorption-in-upper-mesophyll-limits-co2-drawdown-and-depresses-photosynthesis
#8
Jeffrey Mason Earles, Guillaume Théroux-Rancourt, Matthew E Gilbert, Andrew J McElrone, Craig Brodersen
In agricultural and natural systems, diffuse light can enhance plant primary productivity due to deeper penetration into and greater illumination of the entire canopy. However, for individual sun-grown leaves from three species, photosynthesis is actually less efficient under diffuse compared to direct light. Despite its potential impact on canopy-level productivity, the mechanism for this leaf-level 'diffuse light photosynthetic depression' effect is unknown. Here we investigate if the spatial distribution of light absorption relative to electron transport capacity in sun- and shade-grown H...
April 21, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28432218/dynamics-of-growth-zone-patterning-in-the-milkweed-bug-oncopeltus-fasciatus
#9
Tzach Auman, Barbara M I Vreede, Aryeh Weiss, Susan D Hester, Terri A Williams, Lisa M Nagy, Ariel D Chipman
We describe the dynamic process of abdominal segment generation in the milkweed bug Oncopeltus fasciatus We present detailed morphological measurements of the growing germband throughout segmentation. Our data are complemented by cell division profiles and expression patterns of key genes, including invected and even-skipped as markers for different stages of segment formation. We describe morphological and mechanistic changes in the growth zone and in nascent segments during generation of individual segments and throughout segmentation, and examine the relative contribution of newly formed versus existing tissue to segment formation...
April 21, 2017: Development
https://www.readbyqxmd.com/read/28432143/focal-local-field-potential-lfp-signature-of-the-single-axon-monosynaptic-thalamocortical-connection
#10
Espen Hagen, Janne C Fossum, Klas H Pettersen, Jose-Manuel Alonso, Harvey A Swadlow, Gaute T Einevolla
Recent years have seen a resurgence in use of the extracellularly recorded local field potential (LFP) to investigate neural network activity. To probe monosynaptic thalamic activation of cortical postsynaptic target cells, so called spike-trigger-averaged LFP (stLFP) signatures have been measured. In these experiments the cortical LFP is measured by means of multielectrodes covering several cortical lamina and averaged on spontaneous spikes of thalamocortical (TC) cells. Using a well-established forward-modeling scheme, we investigate the biophysical origin of this stLFP signature with simultaneous synaptic activation of cortical layer 4 neurons, mimicking the effect of a single afferent spike from a single TC neuron...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432125/sequential-adaptive-changes-in-a-c-myc-driven-model-of-hepatocellular-carcinoma
#11
James M Dolezal, Huabo Wang, Sucheta Kulkarni, Laura Jackson, Jie Lu, Sarangarajan Ranganathan, Eric S Goetzman, Sivakama Bharathi, Kevin Beezhold, Craig A Byersdorfer, Edward V Prochownik
Hepatocellular carcinoma (HCC) is a common cancer that frequently over-expresses the c-Myc (Myc) oncoprotein. Using a mouse model of Myc-induced HCC, we studied the metabolic, biochemical and molecular changes accompanying HCC progression, regression and recurrence. These involved altered rates of pyruvate and fatty acid β-oxidation and the likely re-directing of glutamine into biosynthetic rather than energy-generating pathways. Initial tumors also showed reduced mitochondrial mass and differential contributions of electron transport chain Complexes I and II to respiration...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432097/diazotrophy-overcomes-the-deleterious-growth-phenotype-of-glne-deletion-in-azotobacter-vinelandii
#12
Florence Mus, Alex Tseng, Ray Dixon, John W Peters
Overcoming the inhibitory effects of excess environmental ammonium on nitrogenase synthesis or activity, or preventing ammonium assimilation, have both been considered as strategies to increase the amount of fixed nitrogen transferred from bacterial to plant partners in associative or symbiotic plant-diazotroph relationships. The GlnE adenylyltransferase/adenylyl-removing enzyme catalyzes reversible adenylylation of glutamine synthetase (GS), thereby affecting the post translational regulation of ammonium assimilation critical for appropriate coordination of carbon and nitrogen assimilation...
April 21, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28432072/translocase-of-inner-membrane-50-functions-as-a-novel-protective-regulator-of-pathological-cardiac-hypertrophy
#13
Kai Tang, Yifan Zhao, Hailing Li, Mengyun Zhu, Weiming Li, Weijing Liu, Guofu Zhu, Dachun Xu, Wenhui Peng, Ya-Wei Xu
BACKGROUND: Translocase of inner membrane 50 (TIM50) is a member of the translocase of inner membrane (TIM) complex in the mitochondria. Previous research has demonstrated the role of TIM50 in the regulation of oxidative stress and cardiac morphology. However, the role of TIM50 in pathological cardiac hypertrophy remains unknown. METHODS AND RESULTS: In the present study we found that the expression of TIM50 was downregulated in hypertrophic hearts. Using genetic loss-of-function animal models, we demonstrated that TIM50 deficiency increased heart and cardiomyocyte size with more severe cardiac fibrosis compared with wild-type littermates...
April 21, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28432011/what-is-an-affordance-40-years-later
#14
REVIEW
François Osiurak, Yves Rossetti, Arnaud Badets
About 40 years ago, James J. Gibson coined the term "affordance" to describe the action possibilities offered to an animal by the environment with reference to the animal's action capabilities. Since then, this notion has acquired a multitude of meanings, generating confusion in the literature. Here, we offer a clear operationalization of the concept of affordances and related concepts in the field of tool use. Our operationalization is organized around the distinction between the physical (what is objectively observable) and neurocognitive (what is subjectively experienced) levels...
April 18, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28431973/understanding-the-relationship-of-cigarette-smoking-trajectories-through-adolescence-and-weight-status-in-young-adulthood-in-the-united-states
#15
Minal Patel, Annette Kaufman, Yvonne Hunt, Linda Nebeling
PURPOSE: Adolescent cigarette smoking has steadily declined since 1999, whereas adolescent obesity rates have quadrupled since the 1980s. Few studies address the longitudinal relationship of smoking and weight in youth and young adulthood. This study examines the relationship of smoking trajectories beginning in adolescence on weight status in young adulthood in a nationally representative longitudinal sample. METHODS: The study sample was drawn from the National Longitudinal Study of Adolescent to Adult Health Waves I-IV (N = 13,361)...
April 18, 2017: Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine
https://www.readbyqxmd.com/read/28431965/origin-of-nanodroplet-formation-upon-dissolution-of-an-amorphous-solid-dispersion-a-mechanistic-isotope-scrambling-study
#16
Anura S Indulkar, Jan E Waters, Huaping Mo, Yi Gao, Shweta A Raina, Geoff G Z Zhang, Lynne S Taylor
It has been observed that certain amorphous solid dispersions (ASDs), upon dissolution, generate drug-rich amorphous nanodroplets. These nanodroplets, present as a dispersed phase, can potentially enhance oral bioavailability of poorly soluble drugs by serving as a drug reservoir that efficiently feeds the continuous aqueous solution phase following absorption of drug. The purpose of this study was to probe the formation mechanism of the nanodroplets. The model system studied was nifedipine (NFD) formulated as an ASD with hydroxypropyl methylcellulose E5 Premium LV (HPMC-E5) or polyvinylpyrrolidone/vinyl acetate (PVPVA)...
April 18, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28431923/sources-of-racial-disparities-in-hiv-prevalence-in-men-who-have-sex-with-men-in-atlanta-ga-usa-a-modelling-study
#17
Steven M Goodreau, Eli S Rosenberg, Samuel M Jenness, Nicole Luisi, Sarah E Stansfield, Gregorio A Millett, Patrick S Sullivan
BACKGROUND: In the USA, men who have sex men (MSM) are at high risk for HIV, and black MSM have a substantially higher prevalence of infection than white MSM. We created a simulation model to assess the strength of existing hypotheses and data that account for these disparities. METHODS: We built a dynamic, stochastic, agent-based network model of black and white MSM aged 18-39 years in Atlanta, GA, USA, that incorporated race-specific individual and dyadic-level prevention and risk behaviours, network attributes, and care patterns...
April 18, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28431862/application-of-the-cdc-ebolaresponse-modeling-tool-to-disease-predictions
#18
Robert H Gaffey, Cécile Viboud
Model-based predictions were critical in eliciting a vigorous international public health response to the 2014 Ebola Virus Disease outbreak in West Africa. Here, we describe the performances of an extension of the CDC-initiated EbolaResponse Modeling tool to the Ebola Forecasting Challenge, which offered a controlled environment for epidemiological predictions. In the EbolaResponse tool, transmission risks and proportions of population affected by interventions were fitted to data via least square fitting. Prediction performances were evaluated for 5 prediction time points of 4 synthetic outbreaks...
March 10, 2017: Epidemics
https://www.readbyqxmd.com/read/28431857/modeling-human-infertility-with-pluripotent-stem-cells
#19
Di Chen, Joanna J Gell, Yu Tao, Enrique Sosa, Amander T Clark
Human fertility is dependent upon the correct establishment and differentiation of the germline. This is because no other cell type in the body is capable of passing a genome and epigenome from parent to child. Terminally differentiated germline cells in the adult testis and ovary are called gametes. However, the initial specification of germline cells occurs in the embryo around the time of gastrulation. Most of our knowledge regarding the cell and molecular events that govern human germline specification involves extrapolating scientific principles from model organisms, most notably the mouse...
April 13, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28431793/alcohol-effects-on-the-epigenome-in-the-germline-role-in-the-inheritance-of-alcohol-related-pathology
#20
REVIEW
Lucy G Chastain, Dipak K Sarkar
Excessive alcohol exposure has severe health consequences, and clinical and animal studies have demonstrated that disruptions in the epigenome of somatic cells, such as those in brain, are an important factor in the development of alcohol-related pathologies, such as alcohol-use disorders (AUDs) and fetal alcohol spectrum disorders (FASDs). It is also well known that alcohol-related health problems are passed down across generations in human populations, but the complete mechanisms for this phenomenon are currently unknown...
March 6, 2017: Alcohol
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