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https://www.readbyqxmd.com/read/29238696/identification-of-clinically-approved-drugs-indacaterol-and-canagliflozin-for-repurposing-to-treat-epidermal-growth-factor-tyrosine-kinase-inhibitor-resistant-lung-cancer
#1
Hongjian Li, Christy Wing-Sum Tong, Yee Leung, Man-Hon Wong, Kenneth Kin-Wah To, Kwong-Sak Leung
In advanced lung cancer, epidermal growth factor tyrosine kinase inhibitors (EGFR TKIs) have extraordinary clinical efficacy. However, their usefulness is severely compromised by drug resistance mediated by various mechanisms, the most important of which is the secondary EGFR T790M mutation. The mutation blocks the binding of EGFR TKIs to the receptor kinase, thereby abolishing the therapeutic efficacy. In this study, we used our free and open-source protein-ligand docking software idock to screen worldwide approved small-molecule drugs against EGFR T790M...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29235174/big-data-and-medicine-a-big-deal
#2
Viktor Mayer-Schönberger, Erik Ingelsson
Big Data promises huge benefits for medical research. Looking beyond superficial increases in the amount of data collected, we identify three key areas where Big Data differs from conventional analyses of data samples: (1) data is captured more comprehensively relative to the phenomenon under study; this reduces some bias but surfaces important tradeoffs, such as between data quantity and data quality; (2) data is often analyzed using machine learning tools, such as neural networks rather than conventional statistical methods resulting in systems that over time capture insights implicit in data, but remain black boxes, rarely revealing causal connections; and (3) the purpose of the analyses of data is no longer simply answering existing questions, but hinting at novel ones and generating promising new hypotheses...
December 13, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29234575/involvement-of-two-uptake-mechanisms-of-gold-and-iron-oxide-nanoparticles-in-a-co-exposure-scenario-using-mouse-macrophages
#3
Dimitri Vanhecke, Dagmar A Kuhn, Dorleta Jimenez de Aberasturi, Sandor Balog, Ana Milosevic, Dominic Urban, Diana Peckys, Niels de Jonge, Wolfgang J Parak, Alke Petri-Fink, Barbara Rothen-Rutishauser
Little is known about the simultaneous uptake of different engineered nanoparticle types, as it can be expected in our daily life. In order to test such co-exposure effects, murine macrophages (J774A.1 cell line) were incubated with gold (AuNPs) and iron oxide nanoparticles (FeO x NPs) either alone or combined. Environmental scanning electron microscopy revealed that single NPs of both types bound within minutes on the cell surface but with a distinctive difference between FeO x NPs and AuNPs. Uptake analysis studies based on laser scanning microscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry revealed intracellular appearance of both NP types in all exposure scenarios and a time-dependent increase...
2017: Beilstein Journal of Nanotechnology
https://www.readbyqxmd.com/read/29230649/investigating-monsoon-and-post-monsoon-variabilities-of-bacterioplankton-communities-in-a-mangrove-ecosystem
#4
Anwesha Ghosh, Punyasloke Bhadury
In mangrove environments, bacterioplankton communities constitute an important component of aquatic biota and play a major role in ecosystem processes. Variability of bacterioplankton communities from Sundarbans mangrove, located in the Indian subcontinent in South Asia and sits on the apex of Bay of Bengal, was investigated over monsoon and post-monsoon seasons. The study was undertaken in two stations in Sundarbans using 16S rRNA clone library and Illumina MiSeq approaches with focus on the functionally important members that participate in coastal biogeochemical cycling...
December 11, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29230574/pigeons-columba-livia-know-when-they-will-need-hints-prospective-metacognition-for-reference-memory
#5
Sumie Iwasaki, Sota Watanabe, Kazuo Fujita
Despite their impressive cognitive abilities, avian species have shown less evidence for metacognition than mammals. We suspect that commonly used tasks such as matching to sample might be too demanding to allow metacognitive processing within birds' working memory. Here, we examined whether pigeons could control their behavior as a function of knowledge levels on a three-item sequence learning task, a reference memory task supposedly requiring fewer working memory resources. The experiment used two types of lists differing in familiarity...
December 11, 2017: Animal Cognition
https://www.readbyqxmd.com/read/29227178/neuronal-pathophysiology-featuring-prpc-and-its-control-over-ca2-metabolism
#6
Alessandro Bertoli, M Catia Sorgato
Calcium (Ca2+) is an intracellular second messenger that ubiquitously masters remarkably diverse biological processes, including cell death. Growing evidence substantiates an involvement of the prion protein (PrPC) in regulating neuronal Ca2+ homeostasis, which could rationalize most of the wide range of functions ascribed to the protein. We have recently demonstrated that PrPC controls extracellular Ca2+ fluxes, and mitochondrial Ca2+ uptake, in neurons stimulated with glutamate (De Mario et al., J Cell Sci 2017; 130:2736-46), suggesting that PrPC protects neurons from threatening Ca2+ overloads and excitotoxicity...
December 11, 2017: Prion
https://www.readbyqxmd.com/read/29225575/investigation-of-naturally-occurring-single-nucleotide-variants-in-human-taar1
#7
Jessica Mühlhaus, Juliane Dinter, Sabine Jyrch, Alexander Teumer, Simon F Jacobi, Georg Homuth, Peter Kühnen, Susanna Wiegand, Annette Grüters, Henry Völzke, Klemens Raile, Gunnar Kleinau, Heiko Krude, Heike Biebermann
Activation of trace amine-associated receptor 1 (TAAR1) in endocrine pancreas is involved in weight regulation and glucose homeostasis. The purpose of this study was the identification and characterization of potential TAAR1 variants in patients with overweight/obesity and disturbed glucose homeostasis. Screening for TAAR1 variants was performed in 314 obese or overweight patients with impaired insulin secretion. The detected variants were functionally characterized concerning TAAR1 cell surface expression and signaling properties and their allele frequencies were determined in the population-based Study of Health in Pomerania (SHIP)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29225129/hydrogen-sulfide-as-a-regulatory-factor-in-kidney-health-and-disease
#8
REVIEW
Balakuntalam S Kasinath, Denis Feliers, Hak Joo Lee
Hydrogen sulfide (H2S) is synthesized in nearly all organ systems including the kidney. Recent findings have revealed that H2S functions as a gasotransmitter affecting a wide range of physiologic functions similar to other gasotransmitters nitric oxide (NO) and carbon monoxide (CO). Research on H2S regulation of kidney function is still in early stages. H2S increases glomerular filtration rate (GFR) and inhibits sodium absorption by the tubules. There is burgeoning evidence that H2S generation by kidney cells is reduced in acute and chronic disease states and that H2S donors ameliorate injury...
December 7, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29222470/remote-control-of-resistive-switching-in-tio2-based-resistive-random-access-memory-device
#9
Dwipak Prasad Sahu, S Narayana Jammalamadaka
We report on the magnetic field control of a bipolar resistive switching in Ag/TiO2/FTO based resistive random access memory device through I-V characteristics. Essentially, in the presence of magnetic field and in the low resistance state, an abrupt change in the resistance of the device demands higher voltage, hinting that residual Lorentz force plays a significant role in controlling the resistance state. Endurance characteristics of the device infer that there is no degradation of the device even after repeated cycling, which ensures that the switching of resistance between 'off' and 'on' states is reproducible, reversible and controllable...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29221123/vegf-induced-intracellular-ca2-oscillations-are-down-regulated-and-do-not-stimulate-angiogenesis-in-breast-cancer-derived-endothelial-colony-forming-cells
#10
Francesco Lodola, Umberto Laforenza, Fabio Cattaneo, Federico Alessandro Ruffinatti, Valentina Poletto, Margherita Massa, Richard Tancredi, Estella Zuccolo, Dlzar Alì Khdar, Alberto Riccardi, Marco Biggiogera, Vittorio Rosti, Germano Guerra, Francesco Moccia
Endothelial colony forming cells (ECFCs) represent a population of truly endothelial precursors that promote the angiogenic switch in solid tumors, such as breast cancer (BC). The intracellular Ca2+ toolkit, which drives the pro-angiogenic response to VEGF, is remodelled in tumor-associated ECFCs such that they are seemingly insensitive to this growth factor. This feature could underlie the relative failure of anti-VEGF therapies in cancer patients. Herein, we investigated whether and how VEGF uses Ca2+ signalling to control angiogenesis in BC-derived ECFCs (BC-ECFCs)...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220677/a-powerful-approach-to-estimating-annotation-stratified-genetic-covariance-via-gwas-summary-statistics
#11
Qiongshi Lu, Boyang Li, Derek Ou, Margret Erlendsdottir, Ryan L Powles, Tony Jiang, Yiming Hu, David Chang, Chentian Jin, Wei Dai, Qidu He, Zefeng Liu, Shubhabrata Mukherjee, Paul K Crane, Hongyu Zhao
Despite the success of large-scale genome-wide association studies (GWASs) on complex traits, our understanding of their genetic architecture is far from complete. Jointly modeling multiple traits' genetic profiles has provided insights into the shared genetic basis of many complex traits. However, large-scale inference sets a high bar for both statistical power and biological interpretability. Here we introduce a principled framework to estimate annotation-stratified genetic covariance between traits using GWAS summary statistics...
December 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29220487/ancestral-genome-estimation-reveals-the-history-of-ecological-diversification-in-agrobacterium
#12
Florent Lassalle, Rémi Planel, Simon Penel, David Chapulliot, Valérie Barbe, Audrey Dubost, Alexandra Calteau, David Vallenet, Damien Mornico, Thomas Bigot, Laurent Guéguen, Ludovic Vial, Daniel Muller, Vincent Daubin, Xavier Nesme
Horizontal gene transfer (HGT) is considered as a major source of innovation in bacteria, and as such is expected to drive adaptation to new ecological niches. However, among the many genes acquired through HGT along the diversification history of genomes, only a fraction may have actively contributed to sustained ecological adaptation. We used a phylogenetic approach accounting for the transfer of genes (or groups of genes) to estimate the history of genomes in Agrobacterium biovar 1, a diverse group of soil and plant-dwelling bacterial species...
December 6, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29219541/spatiotemporal-self-organization-of-fluctuating-bacterial-colonies
#13
Tobias Grafke, Michael E Cates, Eric Vanden-Eijnden
We model an enclosed system of bacteria, whose motility-induced phase separation is coupled to slow population dynamics. Without noise, the system shows both static phase separation and a limit cycle, in which a rising global population causes a dense bacterial colony to form, which then declines by local cell death, before dispersing to reinitiate the cycle. Adding fluctuations, we find that static colonies are now metastable, moving between spatial locations via rare and strongly nonequilibrium pathways, whereas the limit cycle becomes almost periodic such that after each redispersion event the next colony forms in a random location...
November 3, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/29219376/absence-of-marginal-stability-in-a-structural-glass
#14
Camille Scalliet, Ludovic Berthier, Francesco Zamponi
Marginally stable solids have peculiar physical properties that were first analyzed in the context of the jamming transition. We theoretically investigate the existence of marginal stability in a prototypical model for structural glass formers, combining analytical calculations in infinite dimensions to computer simulations in three dimensions. While mean-field theory predicts the existence of a Gardner phase transition towards a marginally stable glass phase at low temperatures, simulations show no hint of diverging time scales or length scales, but reveal instead the presence of sparse localized defects...
November 17, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/29218753/neuronal-responses-to-the-scratching-and-caressing-of-one-s-own-skin-in-patients-with-skin-picking-disorder
#15
Anne Schienle, Sonja Übel, Albert Wabnegger
Skin-picking disorder (SPD) is a common mental disorder. The predominant symptom involves the repeated scratching and picking of one's own skin. This behavior causes severe tissue damage (sores, scars, and infections), often leading to disfigurement. Besides physical injury, SPD is associated with clinically significant distress and impairment in important areas of functioning. The neurobiological mechanisms of SPD are still poorly understood. In this study, 30 SPD patients and 31 control participants (35 women, 26 men) with a mean age of 34 years were instructed to either scratch or gently stroke a small skin area on their arms during functional magnetic resonance imaging...
December 7, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/29217161/mir-1202-suppresses-hepatocellular-carcinoma-cells-migration-and-invasion-by-targeting-cyclin-dependent-kinase-14
#16
Bo Du, Peng Zhang, Zhiming Tan, Jifan Xu
Currently, hepatocellular carcinoma (HCC) patients still have poor survival outcomes mainly due to the powerful mobility of HCC cells. Increasing evidences hint that abnormally expressed miRNAs are capable to modulate HCC cells invasion and migration. MiR-1202 has been proposed as a ponderable molecular tumor marker in a variety of tumors. Here, results from real-time PCR indicated the decreased expression of miR-1202 in HCC. Clinically, statistical analysis showed that miR-1202 under-expression was closely associated with metastasis-related clinicopathologic characteristics...
December 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29215202/context-dependent-vertical-transmission-shapes-strong-endosymbiont-community-structure-in-the-pea-aphid-acyrthosiphon-pisum
#17
Danielle I Rock, Andrew H Smith, Jonah Joffe, Amie Albertus, Narayan Wong, Michael O'Connor, Kerry M Oliver, Jacob A Russell
Animal-associated microbiomes are often comprised of structured, multi-species communities, with particular microbes showing trends of co-occurrence or exclusion. Such structure suggests variable community stability, or variable costs and benefits-possibilities with implications for symbiont-driven host adaptation. In this study, we performed systematic screening for maternally transmitted, facultative endosymbionts of the pea aphid, Acyrthosiphon pisum. Sampling across six locales, with up to five years of collection in each, netted significant and consistent trends of community structure...
December 7, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/29215039/semantic-discrimination-impacts-tdcs-modulation-of-verb-processing
#18
Valentina Niccolai, Anne Klepp, Peter Indefrey, Alfons Schnitzler, Katja Biermann-Ruben
Motor cortex activation observed during body-related verb processing hints at simulation accompanying linguistic understanding. By exploiting the up- and down-regulation that anodal and cathodal transcranial direct current stimulation (tDCS) exert on motor cortical excitability, we aimed at further characterizing the functional contribution of the motor system to linguistic processing. In a double-blind sham-controlled within-subjects design, online stimulation was applied to the left hemispheric hand-related motor cortex of 20 healthy subjects...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29211688/possible-half-metallicity-and-variable-range-hopping-transport-in-sb-substituted-fe2tisn-heusler-alloys
#19
S Chaudhuri, P A Bhobe, A K Nigam
The investigation of the magnetotransport properties on [Formula: see text] [Formula: see text]Sb x with 0 [Formula: see text] 0.6 are presented in this paper. The substitution of Sb in place of Sn decreases the anti-site disorder as evident from x-ray diffraction patterns as well as from transport properties measurement. The much-disputed upturn in low temperature electrical resistivity of [Formula: see text]TiSn has been demonstrated to be a result of weak localization induced by anti-site disorder. With increased Sb substitution (⩾25%) the metallic transport behavior of [Formula: see text]TiSn changes to semiconductor-like...
December 6, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/29210952/survey-of-the-american-neurotology-society-on-cochlear-implantation-part-1-candidacy-assessment-and-expanding-indications
#20
Matthew L Carlson, Douglas P Sladen, Richard K Gurgel, Nicole M Tombers, Christine M Lohse, Colin L Driscoll
OBJECTIVE: To examine practice variance of cochlear implant candidacy assessment and off-label indications across centers in the United States. METHODS: Cross-sectional survey of the American Neurotology Society (ANS). RESULTS: A total of 81 surveys were returned from ANS members who report regular involvement in cochlear implant care. Overall there was a broad distribution in age and clinical experience, with most respondents reporting ACGME accreditation in neurotology and employment at an academic center...
November 28, 2017: Otology & Neurotology
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