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https://www.readbyqxmd.com/read/28806064/conditional-displacement-hybridization-assay-for-multiple-snp-phasing
#1
Tsz Wing Fan, Henson L Lee Yu, I-Ming Hsing
The two chromosomal copies of the human genome are highly polymorphic, and the allelic content on each strand can dictate a person's biological outcomes. While many of the current diagnostic tools are able to detect the presence of multiple mutations at the same time, most cannot determine the phase of these mutations unless long-range PCR or sequencing techniques are used or if templates are compartmentalized into single copies prior to amplification. Here, an enzyme-coupled hybridization assay, named Conditional Displacement Hybridization Assay (CDHA), is described for the concurrent and rapid determination of the presence and phase of SNP variants...
August 14, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28805880/vacuum-filling-of-complex-microchannels-with-liquid-metal
#2
Yiliang Lin, Olivia Gordon, M Rashed Khan, Neyanel Vasquez, Jan Genzer, Michael D Dickey
This paper describes the utilization of vacuum to fill complex microchannels with liquid metal. Microchannels filled with liquid metal are useful as conductors for soft and stretchable electronics, as well as for microfluidic components such as electrodes, antennas, pumps, or heaters. Liquid metals are often injected manually into the inlet of a microchannel using a syringe. Injection can only occur if displaced air in the channels has a pathway to escape, which is usually accomplished using outlets. The positive pressure (relative to atmosphere) needed to inject fluids can also cause leaks or delamination of the channels during injection...
August 14, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28805868/a-microfluidic-flow-cytometer-enabling-absolute-quantification-of-single-cell-intracellular-proteins
#3
Xiufeng Li, Beiyuan Fan, Shanshan Cao, Deyong Chen, Xiaoting Zhao, Dong Men, Wentao Yue, Junbo Wang, Jian Chen
Quantification of single-cell proteomics provides key insights into cellular heterogeneity while conventional flow cytometry cannot provide absolute quantification of intracellular proteins of single cells due to the lack of calibration approaches. This paper presents a constriction channel (with a cross sectional area smaller than cells) based microfluidic flow cytometer, capable of collecting copy numbers of specific intracellular proteins. In this platform, single cells stained with fluorescence labelled antibodies were forced to squeeze through the constriction channel with the fluorescence intensities quantified and since cells fully filled the constriction channel during the squeezing process, solutions with fluorescence labelled antibodies were flushed into the constriction channel to obtain calibration curves...
August 14, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28805468/long-term-persistence-with-single-pill-fixed-dose-combination-therapy-versus-two-pills-of-amlodipine-and-perindopril-for-hypertension-australian-experience
#4
Leon A Simons, Eric Chung, Michael Ortiz
OBJECTIVE: To study treatment persistence and mortality using a single-pill, fixed-dose combination tablet compared with a two-pill combination for hypertension. RESEARCH DESIGN AND METHODS: We analyzed Australian Pharmaceutical Benefit Scheme records 2011-2014 in a 10% random sample of concessional patients prescribed concomitant amlodipine and perindopril - either as a single-pill, fixed-dose combination tablet (n = 9340) or as two-pill combination therapy (n = 3093)...
August 14, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28804757/one-aptamer-two-functions-the-full-length-aptamer-inhibits-ampa-receptors-while-the-short-one-inhibits-both-ampa-and-kainate-receptors
#5
William J Jaremko, Zhen Huang, Wei Wen, Andrew Wu, Nicholas Karl, Li Niu
AMPA and kainate receptors, along with NMDA receptors, are distinct subtypes of glutamate ion channels. Excessive activity of AMPA and kainate receptors has been implicated in neurological diseases, such as epilepsy and neuropathic pain. Antagonists that block their activities are therefore potential drug candidates. In a recent article in the Journal of Biological Chemistry by Jaremko et al. 2017, we have reported on the discovery and molecular characterization of an RNA aptamer of a dual functionality: the full-length RNA (101 nucleotide) inhibits AMPA receptors while the truncated or the short (55 nucleotide) RNA inhibits both the AMPA and kainate receptors...
2017: RNA & Disease
https://www.readbyqxmd.com/read/28803967/igdb-2-an-ig-fniii-protein-binds-the-ion-channel-lgc-34-and-controls-sensory-compartment-morphogenesis-in-c-elegans
#6
Wendy Wang, Elliot A Perens, Grigorios Oikonomou, Yun Lu, Shai Shaham
Sensory organ glia surround neuronal receptive endings (NREs), forming a specialized compartment important for neuronal activity, and reminiscent of glia-ensheathed synapses in the central nervous system. We previously showed that DAF-6, a Patched-related protein, is required in glia of the C. elegans amphid sensory organ to restrict sensory compartment size. LIT-1, a Nemo-like kinase, and SNX-1, a retromer component, antagonize DAF-6 and promote compartment expansion. To further explore the machinery underlying compartment size control, we sought genes whose inactivation restores normal compartment size to daf-6 mutants...
August 10, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28803422/salidroside-improved-cerebrovascular-vasodilation-in-streptozotocin-induced-diabetic-rats-through-restoring-the-function-of-bkca-channel-in-smooth-muscle-cells
#7
Yu-Guang Ma, Jun-Wei Wang, Yin-Bin Zhang, Bao-Feng Wang, Zhi-Jun Dai, Man-Jiang Xie, Hua-Feng Kang
Vessel disease is a kind of severe complication in diabetic patients. However, few pharmacologic agents can directly recover diabetic vascular function. Salidroside (SAL), a major ingredient from Rhodiola rosea, has been found to have an obvious hypoglycemic effect and a beneficial protection on vascular function in diabetes. However, whether SAL is a suitable treatment for diabetes has not so far been evaluated and the underlying mechanisms remain unknown. The present work aims to (1) investigate the potential effects of SAL on cerebrovascular relaxation in streptozotocin-induced diabetic rats or when exposed to acute hyperglycemia condition and (2) examine whether function of the BKCa channel is involved in SAL treatment for diabetic vascular relaxation...
August 12, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28802332/new-algorithms-for-processing-time-series-big-eeg-data-within-mobile-health-monitoring-systems
#8
Mohamed Adel Serhani, Mohamed El Menshawy, Abdelghani Benharref, Saad Harous, Alramzana Nujum Navaz
BACKGROUND AND OBJECTIVES: Recent advances in miniature biomedical sensors, mobile smartphones, wireless communications, and distributed computing technologies provide promising techniques for developing mobile health systems. Such systems are capable of monitoring epileptic seizures reliably, which are classified as chronic diseases. Three challenging issues raised in this context with regard to the transformation, compression, storage, and visualization of big data, which results from a continuous recording of epileptic seizures using mobile devices...
October 2017: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/28800628/genome-wide-analysis-of-sotalol-induced-ikr-inhibition-during-ventricular-repolarization-generepol-study-lack-of-common-variants-with-large-effect-sizes
#9
Joe-Elie Salem, Marine Germain, Jean-Sébastien Hulot, Pascal Voiriot, Bruno Lebourgeois, Jean Waldura, David-Alexandre Tregouet, Beny Charbit, Christian Funck-Brentano
Many drugs used for non-cardiovascular and cardiovascular purposes, such as sotalol, have the side effect of prolonging cardiac repolarization, which can trigger life-threatening cardiac arrhythmias by inhibiting the potassium-channel IKr (KCNH2). On the electrocardiogram (ECG), IKr inhibition induces an increase in QTc and Tpeak-Tend (TpTe) interval and a decrease of T wave maximal amplitude (TAmp). These changes vary markedly between subjects, suggesting the existence of predisposing genetic factors. 990 healthy individuals, prospectively challenged with an oral 80mg sotalol dose, were monitored for changes in ventricular repolarization on ECG between baseline and 3 hours post dosing...
2017: PloS One
https://www.readbyqxmd.com/read/28798968/stretching-of-surface-tethered-polymers-in-pressure-driven-flow-under-confinement
#10
Tamal Roy, Kai Szuttor, Jens Smiatek, Christian Holm, Steffen Hardt
We study the effect of pressure-driven flow on a single surface-tethered DNA molecule confined between parallel surfaces. The influence of flow and channel parameters as well as the length of the molecules on their extension and orientation is explored. In the experiments the chain conformations are imaged by laser scanning confocal microscopy. We find that the fractional extension of the tethered DNA molecules mainly depends on the wall shear stress, with effects of confinement being very weak. Experiments performed with molecules of different contour length show that the fractional extension is a universal function of the product of the wall shear stress and the contour length, a result that can be obtained from a simple scaling relation...
August 11, 2017: Soft Matter
https://www.readbyqxmd.com/read/28798297/crystal-structure-of-mppr-1i-a-scp-taps-protein-from-moniliophthora-perniciosa-the-fungus-that-causes-witches-broom-disease-of-cacao
#11
Renata M Baroni, Zhipu Luo, Rabih Darwiche, Elissa M Hudspeth, Roger Schneiter, Gonçalo A G Pereira, Jorge M C Mondego, Oluwatoyin A Asojo
The pathogenic fungi Moniliophthora perniciosa causes Witches' Broom Disease (WBD) of cacao. The structure of MpPR-1i, a protein expressed by M. perniciosa when it infects cacao, are presented. This is the first reported de novo structure determined by single-wavelength anomalous dispersion phasing upon soaking with selenourea. Each monomer has flexible loop regions linking the core alpha-beta-alpha sandwich topology that comprise ~50% of the structure, making it difficult to generate an accurate homology model of the protein...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28795510/cngb3-mutation-spectrum-including-copy-number-variations-in-485-achromatopsia-patients
#12
Anja Kathrin Mayer, Caroline Van Cauwenbergh, Christine Rother, Britta Baumann, Peggy Reuter, Elfride De Baere, Bernd Wissinger, Susanne Kohl
Achromatopsia is a rare autosomal recessive cone disorder characterized by color vision defects, photophobia, nystagmus and severely reduced visual acuity. The disease is caused by mutations in genes encoding crucial components of the cone phototransduction cascade (CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H) or in ATF6, involved in the unfolded protein response. CNGB3 encoding the beta subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors is the major achromatopsia gene. Here, we present a comprehensive spectrum of CNGB3 mutations and their prevalence in a cohort of 1,074 independent families clinically diagnosed with achromatopsia...
August 10, 2017: Human Mutation
https://www.readbyqxmd.com/read/28795245/a-systematic-review-and-meta-analysis-of-the-treatment-of-anal-fissure
#13
REVIEW
R L Nelson, D Manuel, C Gumienny, B Spencer, K Patel, K Schmitt, D Castillo, A Bravo, A Yeboah-Sampong
BACKGROUND: Anal fissure has a very large number of treatment options. The choice is difficult. In an effort to assist in that, choice presented here is a systematic review and meta-analysis of all published treatments for anal fissure that have been studied in randomized controlled trials. METHODS: Randomized trials were sought in the Cochrane Controlled Trials Register, Medline, EMBASE and the trials registry sites clinicaltrials.gov and who/int/ictrp/search/en...
August 9, 2017: Techniques in Coloproctology
https://www.readbyqxmd.com/read/28792226/single-electron-transistor-with-single-aromatic-ring-molecule-covalently-connected-to-graphene-nanogaps
#14
Qizhi Xu, Giovanni Scuri, Carly Mathewson, Philip Kim, Colin Nuckolls, Delphine Bouilly
We report a robust approach to fabricate single-molecule transistors with covalent electrode-molecule-electrode chemical bonds, ultrashort (∼1 nm) molecular channels, and high coupling yield. We obtain nanometer-scale gaps from feedback-controlled electroburning of graphene constrictions and bridge these gaps with molecules using reaction chemistry on the oxidized graphene edges. Using these nanogaps, we are able to optimize the coupling chemistry to achieve high reconnection yield with ultrashort covalent single-molecule bridges...
August 9, 2017: Nano Letters
https://www.readbyqxmd.com/read/28792054/droplet-trapping-and-fast-acoustic-release-in-a-multi-height-device-with-steady-state-flow
#15
Richard W Rambach, Kevin Linder, Michael Heymann, Thomas Franke
We demonstrate a novel multilayer polydimethylsiloxane (PDMS) device for selective storage and release of single emulsion droplets. Drops are captured in a microchannel cavity and can be released on-demand through a triggered surface acoustic wave pulse. The surface acoustic wave (SAW) is excited by a tapered interdigital transducer (TIDT) deposited on a piezoelectric lithium niobate (LiNbO3) substrate and inverts the pressure difference across the cavity trap to push a drop out of the trap and back into the main flow channel...
August 9, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28789534/excited-state-wavepacket-dynamics-in-no2-probed-by-strong-field-ionization
#16
Ruaridh Forbes, Andrey E Boguslavskiy, Iain Wilkinson, Jonathan G Underwood, Albert Stolow
We present an experimental femtosecond time-resolved study of the 399 nm excited state dynamics of nitrogen dioxide using channel-resolved above threshold ionization (CRATI) as the probe process. This method relies on photoelectron-photoion coincidence and covariance to correlate the strong-field photoelectron spectrum with ionic fragments, which label the channel. In all ionization channels observed, we report apparent oscillations in the ion and photoelectron yields as a function of pump-probe delay. Further, we observe the presence of a persistent, time-invariant above threshold ionization comb in the photoelectron spectra associated with most ionization channels at long time delays...
August 7, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28783319/sharper-reaction-monitoring-generation-of-a-narrow-line-width-nmr-singlet-without-x-pulses-in-an-inhomogeneous-magnetic-field
#17
Ariana B Jones, Guy C Lloyd-Jones, Dusan Uhrin
We report a new 'pure-shift' method, termed 'SHARPER' (Sensitive, Homogeneous And Resolved PEaks in Real time) de-signed for the analysis of reactions and equilibria by NMR. By focusing on a single selected signal, SHARPER removes all heteronuclear couplings of a selected nucleus without the need to pulse on X channels, thus overcoming hardware limitations of conventional spectrometers. A more versatile decoupling scheme, termed 'sel-SHARPER', removes all heteronuclear and homonuclear couplings of the selected signal...
August 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28783259/anticipating-cutoff-diameters-in-deterministic-lateral-displacement-dld-microfluidic-devices-for-an-optimized-particle-separation
#18
Eloise Pariset, Catherine Pudda, François Boizot, Nicolas Verplanck, Jean Berthier, Aurélie Thuaire, Vincent Agache
Deterministic lateral displacement (DLD) devices enable to separate nanometer to micrometer-sized particles around a cutoff diameter, during their transport through a microfluidic channel with slanted rows of pillars. In order to design appropriate DLD geometries for specific separation sizes, robust models are required to anticipate the value of the cutoff diameter. So far, the proposed models result in a single cutoff diameter for a given DLD geometry. This paper shows that the cutoff diameter actually varies along the DLD channel, especially in narrow pillar arrays...
August 7, 2017: Small
https://www.readbyqxmd.com/read/28782041/a-bimodal-activation-mechanism-underlies-scorpion-toxin-induced-pain
#19
Shilong Yang, Fan Yang, Bei Zhang, Bo Hyun Lee, Bowen Li, Lei Luo, Jie Zheng, Ren Lai
Venomous animals use peptide toxins for hunting and self-defense. To achieve these goals, toxins need to bind to their targets with high affinity due to the small amount that a single bite or sting can deliver. The scorpion toxin BmP01 is linked to sting-induced excruciating pain; however, the reported minimum concentrations for activating TRPV1 channel or inhibiting voltage-gated potassium (Kv) channels (both in the micromolar range) appear too high to be biologically relevant. We show that the effective concentration of BmP01 is highly pH-dependent-it increases by about 10-fold in inhibiting Kv channels upon a 1-U drop in pH but decreases more than 100-fold in activating TRPV1...
August 2017: Science Advances
https://www.readbyqxmd.com/read/28781163/polypharmacology-of-conformationally-locked-methanocarba-nucleosides
#20
REVIEW
Kenneth A Jacobson, Dilip K Tosh, Kiran S Toti, Antonella Ciancetta
A single molecular scaffold can be adapted to interact with diverse targets, either separately or simultaneously. Nucleosides and nucleotides in which ribose is substituted with bicyclo[3.1.0]hexane are an example of a versatile drug-like scaffold for increasing selectivity at their classical targets: kinases, polymerases, adenosine and P2 receptors. Also, by applying structure-based functional group manipulations, rigidified adenosine derivatives can be repurposed to satisfy pharmacophoric requirements of various GPCRs, ion channels, enzymes and transporters, initially detected as off-target activities...
August 3, 2017: Drug Discovery Today
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