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https://www.readbyqxmd.com/read/28423742/novel-potential-predictive-markers-of-sunitinib-outcomes-in-long-term-responders-versus-primary-refractory-patients-with-metastatic-clear-cell-renal-cell-carcinoma
#1
Javier Puente, Nuria Laínez, Marta Dueñas, María José Méndez-Vidal, Emilio Esteban, Daniel Castellano, Mónica Martinez-Fernández, Laura Basterretxea, María José Juan-Fita, Luis Antón, Luis León, Julio Lambea, Begoña Pérez-Valderrama, Sergio Vázquez, Cristina Suarez, Xavier Garcia Del Muro, Enrique Gallardo, José Pablo Maroto, M Luz Samaniego, Beatriz Suárez-Paniagua, Julián Sanz, Jesús M Paramio, Sogug Spanish Oncology Genitourinary Group
BACKGROUND: Several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. PATIENTS AND METHODS: Multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)≥22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset)...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420978/resting-state-fmri-reveals-increased-subthalamic-nucleus-and-sensorimotor-cortex-connectivity-in-patients-with-parkinson-s-disease-under-medication
#2
Bo Shen, Yang Gao, Wenbin Zhang, Liyu Lu, Jun Zhu, Yang Pan, Wenya Lan, Chaoyong Xiao, Li Zhang
Functional connectivity (FC) between the subthalamic nucleus (STN) and the sensorimotor cortex is increased in off-medication patients with Parkinson's disease (PD). However, the status of FC between STN and sensorimotor cortex in on-medication PD patients remains unclear. In this study, resting state functional magnetic resonance imaging was employed on 31 patients with PD under medication and 31 healthy controls. Two-sample t-test was used to study the change in FC pattern of the STN, the FC strength of the bilateral STN was correlated with overall motor symptoms, while unilateral STN was correlated with offside motor symptoms...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28419375/transcriptional-profiling-of-cholinergic-neurons-from-basal-forebrain-identifies-changes-in-expression-of-genes-between-sleep-and-wake-mrna-profiling-in-basal-forebrain-with-sleep-sleep-deprivation
#3
Elena V Nikonova, Jason DA Gilliland, Keith Q Tanis, Alexei A Podtelezhnikov, Alison M Rigby, Raymond J Galante, Eva M Finney, David J Stone, John J Renger, Allan I Pack, Christopher J Winrow
Study objective: To assess differences in gene expression in cholinergic basal forebrain cells between sleeping and sleep deprived mice sacrificed at the same time of day. Methods: Tg(ChAT-eGFP)86Gsat mice expressing eGFP under control of the choline acetyltransferase (Chat) promoter were utilized to guide laser capture of cholinergic cells in basal forebrain. mRNA expression levels in these cells were profiled using microarrays. Gene expression in eGFP(+) neurons was compared (1) to that in eGFP(-) neurons and to adjacent white matter, (2) between 7:00 am (lights on) and 7:00 pm (lights off), (3) between sleep deprived and sleeping animals at 0, 3, 6, 9 hrs from lights on...
April 13, 2017: Sleep
https://www.readbyqxmd.com/read/28419346/our-shared-vulnerability-to-dangerous-pathogens
#4
Lawrence O Gostin
The international community vastly underestimates the risk and scale of our shared vulnerability to fast moving pathogens. Ranging from SARS and novel influenzas to Ebola and Zika, the world seems to be caught off guard, despite the regularity of global health threats historically. More importantly, when governments and international institutions underestimate the threat, they also underinvest in preparedness. Failure to prepare has deep costs in human lives and economic productivity. Here, I offer a pathway to preparedness for, and rapid response to, infectious disease threats: robust and resilient national health systems; strong institutions capable of leading, particularly the World Health Organization; and investments in research and development...
April 17, 2017: Medical Law Review
https://www.readbyqxmd.com/read/28416665/hippo-pathway-mediates-resistance-to-cytotoxic-drugs
#5
Taranjit S Gujral, Marc W Kirschner
Chemotherapy is widely used for cancer treatment, but its effectiveness is limited by drug resistance. Here, we report a mechanism by which cell density activates the Hippo pathway, which in turn inactivates YAP, leading to changes in the regulation of genes that control the intracellular concentrations of gemcitabine and several other US Food and Drug Administration (FDA)-approved oncology drugs. Hippo inactivation sensitizes a diverse panel of cell lines and human tumors to gemcitabine in 3D spheroid, mouse xenografts, and patient-derived xenograft models...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28413956/structure-roles-and-inhibitors-of-a-mitotic-protein-kinase-haspin
#6
Katrin Kestav, Asko Uri, Darja Lavogina
Background Haspin (haploid germ cell-specific nuclear protein kinase) is an atypical serine/threonine-protein kinase that was for a long time considered an inactive pseudokinase due to low degree of structural homology of Haspin with the 'classical' protein kinases. However, the discovery of Haspin-catalyzed phosphorylation of histone H3 at Thr3 residue unveiled importance of Haspin in mitosis and provided yet another link between mitotic phosphorylation pathways and chromatin modifications. Results In this review of 111 publications, we have (1) briefly summarized catalytic properties and physiological roles of Haspin, (2) focussed on the architecture of Haspin and mechanisms behind its substrate recognition, (3) provided detailed insight into the advances in the development and characterization of Haspin-selective inhibitors, and (4) given overview of inhibitor scaffolds that despite targeting other protein kinases feature Haspin as a common off-target...
April 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28413954/computational-models-for-understanding-of-structure-function-and-pharmacology-of-the-cardiac-potassium-channel-kv11-1-herg
#7
Sören Wacker, Sergei Yu Noskov, Laura L Perissinotti
The rapid delayed rectifier current IKr is one of the major K+ currents involved into repolarization of the human cardiac action potential. Various inherited or drug-induced forms of the long QT syndrome (LQTS) in humans are linked to functional and structural modifications in the IKr conducting channels. IKr is carried by the potassium channel Kv11.1 encoded by the gene KCNH2 (commonly referred to as human ether-a-go-go-related gene or hERG) [1][2]. The first necessary step for predicting emergent drug effects on the heart is determining and modeling the binding thermodynamics and kinetics of primary and major off-target drug interactions with subcellular targets...
April 14, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28411619/statistical-properties-of-fluctuating-enzymes-with-dynamic-cooperativity-using-a-first-passage-time-distribution-formalism
#8
Divya Singh, Srabanti Chaudhury
We study the temporal fluctuations in catalytic rates for single enzyme reactions undergoing slow transitions between two active states. We use a first passage time distribution formalism to obtain the closed-form analytical expressions of the mean reaction time and the randomness parameter for reaction schemes where conformational fluctuations are present between two free enzyme conformers. Our studies confirm that the sole presence of free enzyme fluctuations yields a non Michaelis-Menten equation and can lead to dynamic cooperativity...
April 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28411274/posterior-orbitofrontal-and-anterior-cingulate-pathways-to-the-amygdala-target-inhibitory-and-excitatory-systems-with-opposite-functions
#9
Basilis Zikopoulos, Malin Hoistad, Yohan John, Helen Barbas
The bidirectional dialogue of the primate posterior orbitofrontal cortex (pOFC) with the amygdala is essential in cognitive-emotional functions. The pOFC also sends a uniquely one-way excitatory pathway to the amygdalar inhibitory intercalated masses (IM), which inhibit the medial part of the central amygdalar nucleus (CeM). Inhibition of IM has the opposite effect, allowing amygdalar activation of autonomic structures and emotional arousal. Using multiple labeling approaches to identify pathways and their postsynaptic sites in the amygdala in rhesus monkeys we found that the anterior cingulate cortex (ACC) innervated mostly the basolateral and CeM amygdalar nuclei, poised to activate CeM for autonomic arousal...
April 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28408968/effect-of-ring-strain-on-the-charge-transport-of-a-robust-norbornadiene-quadricyclane-based-molecular-photoswitch
#10
Behabitu E Tebikachew, Haipeng B Li, Alessandro Pirrotta, Karl Börjesson, Gemma C Solomon, Joshua Hihath, Kasper Moth-Poulsen
Integrating functional molecules into single-molecule devices is a key step toward the realization of future computing machines based on the smallest possible components. In this context, photoswitching molecules that can make a transition between high and low conductivity in response to light are attractive candidates. Here we present the synthesis and conductance properties of a new type of robust molecular photothermal switch based on the norbornadiene (NB)-quadricyclane (QC) system. The transport through the molecule in the ON state is dominated by a pathway through the π-conjugated system, which is no longer available when the system is switched to the OFF state...
April 6, 2017: Journal of Physical Chemistry. C, Nanomaterials and Interfaces
https://www.readbyqxmd.com/read/28408867/visualization-of-snare-mediated-hemifusion-between-giant-unilamellar-vesicles-arrested-by-myricetin
#11
Paul Heo, Joon-Bum Park, Yeon-Kyun Shin, Dae-Hyuk Kweon
Neurotransmitters are released within a millisecond after Ca(2+) arrives at an active zone. However, the vesicle fusion pathway underlying this synchronous release is yet to be understood. At the center of controversy is whether hemifusion, in which outer leaflets are merged while inner leaflets are still separated, is an on-pathway or off-pathway product of Ca(2+)-triggered exocytosis. Using the single vesicle fusion assay, we recently demonstrated that hemifusion is an on-pathway intermediate that immediately proceeds to full fusion upon Ca(2+) triggering...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28406202/finding-pathways-to-national-scale-land-sector-sustainability
#12
Lei Gao, Brett A Bryan
The 17 Sustainable Development Goals (SDGs) and 169 targets under Agenda 2030 of the United Nations map a coherent global sustainability ambition at a level of detail general enough to garner consensus amongst nations. However, achieving the global agenda will depend heavily on successful national-scale implementation, which requires the development of effective science-driven targets tailored to specific national contexts and supported by strong national governance. Here we assess the feasibility of achieving multiple SDG targets at the national scale for the Australian land-sector...
April 12, 2017: Nature
https://www.readbyqxmd.com/read/28405059/uniform-atomic-layer-deposition-of-al2o3-on-graphene-by-reversible-hydrogen-plasma-functionalization
#13
René H J Vervuurt, Bora Karasulu, Marcel A Verheijen, Wilhelmus Erwin M M Kessels, Ageeth A Bol
A novel method to form ultrathin, uniform Al2O3 layers on graphene using reversible hydrogen plasma functionalization followed by atomic layer deposition (ALD) is presented. ALD on pristine graphene is known to be a challenge due to the absence of dangling bonds, leading to nonuniform film coverage. We show that hydrogen plasma functionalization of graphene leads to uniform ALD of closed Al2O3 films down to 8 nm in thickness. Hall measurements and Raman spectroscopy reveal that the hydrogen plasma functionalization is reversible upon Al2O3 ALD and subsequent annealing at 400 °C and in this way does not deteriorate the graphene's charge carrier mobility...
March 14, 2017: Chemistry of Materials: a Publication of the American Chemical Society
https://www.readbyqxmd.com/read/28404795/dynamics-of-the-interaction-between-cotton-bollworm-helicoverpa-armigera-and-nucleopolyhedrovirus-as-revealed-by-integrated-transcriptomic-and-proteomic-analyses
#14
Longsheng Xing, Chuanfei Yuan, Manli Wang, Zhe Lin, Benchang Shen, Zhihong Hu, Zhen Zou
Over the past decades, Helicoverpa armigera nucleopolyhedrovirus (HearNPV) has been widely used for biocontrol of cotton bollworm, which is one of the most destructive pest insects in agriculture worldwide. However, the molecular mechanism underlying the interaction between HearNPV and host insects remains poorly understood. In this study, high throughput RNA-sequencing was integrated with label-free quantitative proteomics analysis to examine the dynamics of gene expression in the fat body of H. armigera larvae in response to challenge with HearNPV...
April 12, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28402865/inhibition-versus-facilitation-of-contralesional-motor-cortices-in-stroke-deriving-a-model-to-tailor-brain-stimulation
#15
Vishwanath Sankarasubramanian, Andre G Machado, Adriana B Conforto, Kelsey A Potter-Baker, David A Cunningham, Nicole M Varnerin, Xiaofeng Wang, Ken Sakaie, Ela B Plow
OBJECTIVE: The standard approach to brain stimulation in stroke is based on the premise that ipsilesional M1 (iM1) is important for motor function of the paretic upper limb, while contralesional cortices compete with iM1. Therefore, the approach typically advocates facilitating iM1 and/or inhibiting contralesional M1 (cM1). But, this approach fails to elicit much improvement in severely affected patients, who on account of extensive damage to ipsilesional pathways, cannot rely on iM1...
March 21, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/28400576/a-sputtered-silicon-oxide-electrolyte-for-high-performance-thin-film-transistors
#16
Xiaochen Ma, Jiawei Zhang, Wensi Cai, Hanbin Wang, Joshua Wilson, Qingpu Wang, Qian Xin, Aimin Song
Low operating voltages have been long desired for thin-film transistors (TFTs). However, it is still challenging to realise 1-V operation by using conventional dielectrics due to their low gate capacitances and low breakdown voltages. Recently, electric double layers (EDLs) have been regarded as a promising candidate for low-power electronics due to their high capacitance. In this work, we present the first sputtered SiO2 solid-state electrolyte. In order to demonstrate EDL behaviour, a sputtered 200 nm-thick SiO2 electrolyte was incorporated into InGaZnO TFTs as the gate dielectric...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28397117/pcdd-f-formation-during-thermal-desorption-of-p-p-ddt-contaminated-soil
#17
Zhonghua Zhao, Mingjiang Ni, Xiaodong Li, Alfons Buekens, Jianhua Yan
Thermal treatment of polychlorinated biphenyls (PCB) contaminated soil was shown in earlier work to generate polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF). In this study, the PCDD/F were studied arising during the remediation of p,p'-DDT contaminated soil by thermal desorption. Three kinds of soil (sandy, clayey and lateritic soil) were tested to investigate the effect of soil texture on PCDD/F formation. Those soils were artificially polluted with p,p'-DDT, obtaining a concentration level of 100 mg/kg...
April 10, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28392910/drug-shortages-in-israel-regulatory-perspectives-challenges-and-solutions
#18
Eyal Schwartzberg, Denize Ainbinder, Alla Vishkauzan, Ronni Gamzu
BACKGROUND: Pharmaceutical drug shortages (DSs) are a global problem which presents challenges to countries around the world. Shortages of pharmaceutical products may have a direct detrimental impact on public health and patients' wellbeing by causing delayed, or even lack of, treatment. Moreover, DSs may force both patients and caregivers to use unfamiliar drugs, which could lead to medication errors. The objective of our study was to analyze DSs in Israel during the years 2013-2015, assessing their etiology and exploring the steps taken for their mitigation and prevention...
2017: Israel Journal of Health Policy Research
https://www.readbyqxmd.com/read/28382544/in-vitro-and-in-vivo-metabolite-identification-studies-for-the-new-synthetic-opioids-acetylfentanyl-acrylfentanyl-furanylfentanyl-and-4-fluoro-isobutyrylfentanyl
#19
Shimpei Watanabe, Svante Vikingsson, Markus Roman, Henrik Green, Robert Kronstrand, Ariane Wohlfarth
New fentanyl analogs have recently emerged as new psychoactive substances and have caused numerous fatalities worldwide. To determine if the new analogs follow the same metabolic pathways elucidated for fentanyl and known fentanyl analogs, we performed in vitro and in vivo metabolite identification studies for acetylfentanyl, acrylfentanyl, 4-fluoro-isobutyrylfentanyl, and furanylfentanyl. All compounds were incubated at 10 μM with pooled human hepatocytes for up to 5 h. For each compound, four or five authentic human urine samples from autopsy cases with and without enzymatic hydrolysis were analyzed...
April 5, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28381383/serum-soluble-st2-is-a-promising-prognostic-biomarker-in-hbv-related-acute-on-chronic-liver-failure
#20
Shao-Wen Jiang, Peng Wang, Xiao-Gang Xiang, Rui-Dong Mo, Lan-Yi Lin, Shi-San Bao, Jie Lu, Qing Xie
BACKGROUND: The IL-33/ST2 axis is involved in the pathogenesis of many diseases such as autoimmune diseases, cancer, and heart failure. However, studies of the IL-33/ST2 pathway in HBV-related acute-on-chronic liver failure (HBV-ACLF) are lacking. The present study aimed to determine the prognostic role of serum IL-33/soluble ST2 (sST2) in HBV-ACLF. METHODS: Serum levels of IL-33 and sST2 in healthy controls (HC, n=18), chronic hepatitis B (CHB, n=27) and HBV-ACLF (n=51) patients at the 1st and 4th week after enrollment were detected using ELISA, and clinical data were collected...
April 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
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