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https://www.readbyqxmd.com/read/28641402/ec-tagging-allows-cell-type-specific-rna-analysis
#1
Naoki Hida, Mohamed Y Aboukilila, Dana A Burow, Rakesh Paul, Marc M Greenberg, Michael Fazio, Samantha Beasley, Robert C Spitale, Michael D Cleary
Purification of cell type-specific RNAs remains a significant challenge. One solution involves biosynthetic tagging of target RNAs. RNA tagging via incorporation of 4-thiouracil (TU) in cells expressing transgenic uracil phosphoribosyltransferase (UPRT), a method known as TU-tagging, has been used in multiple systems but can have limited specificity due to endogenous pathways of TU incorporation. Here, we describe an alternative method that requires the activity of two enzymes: cytosine deaminase (CD) and UPRT...
June 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28641400/cytosolic-delivery-of-sirna-by-ultra-high-affinity-dsrna-binding-proteins
#2
Nicole J Yang, Monique J Kauke, Fangdi Sun, Lucy F Yang, Katie F Maass, Michael W Traxlmayr, Yao Yu, Yingda Xu, Robert S Langer, Daniel G Anderson, K Dane Wittrup
Protein-based methods of siRNA delivery are capable of uniquely specific targeting, but are limited by technical challenges such as low potency or poor biophysical properties. Here, we engineered a series of ultra-high affinity siRNA binders based on the viral protein p19 and developed them into siRNA carriers targeted to the epidermal growth factor receptor (EGFR). Combined in trans with a previously described endosome-disrupting agent composed of the pore-forming protein Perfringolysin O (PFO), potent silencing was achieved in vitro with no detectable cytotoxicity...
June 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28641386/the-neurosteroid-pregnenolone-reverts-microtubule-derangement-induced-by-the-loss-of-a-functional-cdkl5-iqgap1-complex
#3
Isabella Barbiero, Diana Peroni, Marco Tramarin, Chetan Chandola, Laura Rusconi, Nicoletta Landsberger, Charlotte Kilstrup-Nielsen
CDKL5 is a protein kinase that plays a key role for neuronal functions as testified by the onset of complex neuronal dysfunctions in patients with genetic lesions in CDKL5. Here we identify a novel interactor of CDKL5, IQGAP1, a fundamental regulator of cell migration and polarity. In accordance with a functional role of this interaction, depletion of CDKL5 impairs cell migration and impedes the localization of IQGAP1 at the leading edge. Moreover, we demonstrate that CDKL5 is required for IQGAP1 to form a functional complex with its effectors, Rac1 and the microtubule plus end tracking protein CLIP170...
June 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28641383/neuroprotection-in-stroke-the-importance-of-collaboration-and-reproducibility
#4
Ain A Neuhaus, Yvonne Couch, Gina Hadley, Alastair M Buchan
Acute ischaemic stroke accounts for 6.5 million deaths per year, and by 2030 will result in the annual loss of over 200 million disability-adjusted life years globally. There have been considerable recent advances in the gold standard of acute ischaemic stroke treatment, some aspects of which-aspirin to prevent recurrence, and treating patients in specialized stroke wards-are widely applicable. Recanalization of the occluded artery through thrombolysis and/or endovascular thrombectomy is restricted to only a small proportion of patients, due to contra-indications and the costs associated with establishing the infrastructure to deliver these treatments...
June 20, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28641354/-acute-liver-failure-acute-on-chronic-liver-failure-hepatorenal-syndrome-hepatopulmonary-syndrome-and-portopulmonary-hypertension-artificial-liver-support-on-the-icu
#5
Uwe Lodes, David Jacob, Frank Meyer
Background Acute hepatic dysfunction in the form of acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) is a disease with a high risk of mortality and requires interdisciplinary intensive care. Aim This article explains the nomenclature, pathophysiology, prognosis and possible treatment options of ALF and ACLF, including the possibilities of extracorporeal liver support therapy at the point of liver transplantation (LTx). Method Narrative review with a selective literature review and representative case studies...
June 2017: Zentralblatt Für Chirurgie
https://www.readbyqxmd.com/read/28641333/validation-of-brain-angiotensin-system-blockade-as-a-novel-drug-target-in-pharmacological-treatment-of-neuropsychiatric-disorders
#6
Dominik Wincewicz, Jan J Braszko
Retreat in psychiatric drug development results in innovative medication decline that might be at least partially overcome by adjunct therapy. New evidence from clinical studies has shown a possible role for brain Renin-Angiotensin System (RAS) in both affective and psychotic disorders. Simultaneously, rapidly accumulating data from basic studies indicate effectiveness of central RAS blockade in much broader range of neuropsychiatric disease. Recent findings implicate brain RAS, especially Angiotensin II (Ang II), in neural pathophysiology of mental disorders through neuroendocrine modulation and effects on neurotransmitter release, mostly noradrenaline, acetylcholine and dopamine...
June 22, 2017: Pharmacopsychiatry
https://www.readbyqxmd.com/read/28641312/impact-of-novel-mir-145-3p-regulatory-networks-on-survival-in-patients-with-castration-resistant-prostate-cancer
#7
Yusuke Goto, Akira Kurozumi, Takayuki Arai, Nijiro Nohata, Satoko Kojima, Atsushi Okato, Mayuko Kato, Kazuto Yamazaki, Yasuo Ishida, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki
BACKGROUND: Despite recent advancements, metastatic castration-resistant prostate cancer (CRPC) is not considered curative. Novel approaches for identification of therapeutic targets of CRPC are needed. METHODS: Next-generation sequencing revealed 945-1248 miRNAs from each lethal mCRPC sample. We constructed miRNA expression signatures of CRPC by comparing the expression of miRNAs between CRPC and normal prostate tissue or hormone-sensitive prostate cancer (HSPC)...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28641303/microrna-122a-regulates-zonulin-by-targeting-egfr-in-intestinal-epithelial-dysfunction
#8
Bin Zhang, Yinghai Tian, Ping Jiang, Yanqiong Jiang, Chao Li, Ting Liu, Rujian Zhou, Ning Yang, Xinke Zhou, Zhihua Liu
BACKGROUND/AIMS: This study aimed to investigate the role of microRNA (miR)-122a in regulating zonulin during the modulation of intestinal barrier. METHODS: Zonulin proteins and their target gene expression were analyzed in miR-122a-overexpressing cell lines and in the target gene of epidermal growth factor receptor (EGFR). An mmu-miR-122a intestinal epithelial conditional transgenic (miR-122a-TG) mouse model was established to investigate EGFR and zonulin expression...
June 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28641271/joint-attributes-and-event-analysis-for-multimedia-event-detection
#9
Zhigang Ma, Xiaojun Chang, Zhongwen Xu, Nicu Sebe, Alexander G Hauptmann
Semantic attributes have been increasingly used the past few years for multimedia event detection (MED) with promising results. The motivation is that multimedia events generally consist of lower level components such as objects, scenes, and actions. By characterizing multimedia event videos with semantic attributes, one could exploit more informative cues for improved detection results. Much existing work obtains semantic attributes from images, which may be suboptimal for video analysis since these image-inferred attributes do not carry dynamic information that is essential for videos...
June 15, 2017: IEEE Transactions on Neural Networks and Learning Systems
https://www.readbyqxmd.com/read/28641264/a-single-channel-eog-based-speller
#10
Shenghong He, Yuanqing Li
Electrooculography (EOG) signals, which can be used to infer the intentions of a user based on eye movements, are widely used in human-computer interface (HCI) systems. Most existing EOG-based HCI systems incorporate a limited number of commands because they generally associate different commands with a few different types of eye movements, such as looking up, down, left, or right. This paper presents a novel single-channel EOG-based HCI that allows users to spell asynchronously by only blinking. Forty buttons corresponding to 40 characters displayed to the user via a graphical user interface (GUI) are intensified in a random order...
June 15, 2017: IEEE Transactions on Neural Systems and Rehabilitation Engineering
https://www.readbyqxmd.com/read/28641263/radian-visual-exploration-of-traceroutes
#11
Massimo Candela, Marco Di Bartolomeo, Giuseppe Di Battista, Claudio Squarcella
Several projects deploy probes in the Internet. Probes are systems that continuously perform traceroutes and other networking measurements (e.g. ping) towards selected targets. Measurements can be stored and analyzed to gain knowledge on several aspects of the Internet, but making sense of such data requires suitable methods and tools for exploration and visualization. We present Radian, a tool that allows to visualize traceroute paths at different levels of detail and to animate their evolution during a selected time interval...
June 19, 2017: IEEE Transactions on Visualization and Computer Graphics
https://www.readbyqxmd.com/read/28641253/a-closed-form-solution-to-single-underwater-camera-calibration-using-triple-wavelength-dispersion-and-its-application-to-single-camera-3d-reconstruction
#12
Xida Chen, Yee-Hong Yang
In this paper, we present a new method to estimate the housing parameters of an underwater camera by making full use of triple wavelength dispersion. Our method is based on an important finding that there is a closed-form solution to the distance from the camera center to the refractive interface once the refractive normal is known. The correctness of this finding is mathematically proved in this paper. To our best knowledge, such a finding has not been studied or reported, and hence is never proved theoretically...
June 16, 2017: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
https://www.readbyqxmd.com/read/28641214/motor-system-dysfunction-in-the-schizophrenia-diathesis-neural-systems-to-neurotransmitters
#13
R Abboud, C Noronha, V A Diwadkar
Motor control is a ubiquitous aspect of human function, and from its earliest origins, abnormal motor control has been proposed as being central to schizophrenia. The neurobiological architecture of the motor system is well understood in primates and involves cortical and sub-cortical components including the primary motor cortex, supplementary motor area, dorsal anterior cingulate cortex, the prefrontal cortex, the basal ganglia, and cerebellum. Notably all of these regions are associated in some manner to the pathophysiology of schizophrenia...
April 25, 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28641210/comparative-analysis-of-polyspecificity-of-the-endogenous-trna-synthetase-of-different-expression-host-towards-photocrosslinking-amino-acids-using-an-in-silico-approach
#14
Nadarajan Saravanan Prabhu, Hyungdon Yun
Photo-induced covalent crosslinking has emerged as the powerful strategy for analyzing and characterizing the protein-protein interaction and mapping protein 3D conformations. In the last decades, a number of photocrosslinking amino acids have been reported but only a few have been efficiently utilized for photocrosslinking purposes. Recently, incorporation of diazirine containing photoactivatable analogs such as photo-methionine, photo-leucine, photo-isoleucine and photo-lysine into target proteins were accomplished in live cells (Human A549cells, HEK 293) by depleting corresponding natural amino acid and supplementing these analogs in the medium...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28641156/mild-c-sp-3-h-functionalization-of-dihydrosanguinarine-and-dihydrochelerythrine-for-development-of-highly-cytotoxic-derivatives
#15
Adriana Romo-Pérez, Luis Demetrio Miranda, Alma D Chávez-Blanco, Alfonso Dueñas-González, María Del Rayo Camacho-Corona, Alejandrina Acosta-Huerta, Abraham García
A series of C(6)-substituted dihydrobenzo[c]phenanthridines were synthesized by mild copper-catalyzed C(sp(3))-H functionalization of dihydrosanguinarine (2) and dihydrochelerythrine (3) with certain nucleophiles selected to enhance cytotoxicity against human breast, colorectal, and prostate cancer cell lines. We also investigated the cytotoxicity of our previously reported C(6)-functionalized N-methyl-5,6-dihydrobenzo[c]phenanthridines 1a-1e to perform structure-activity relationship (SAR) studies. Among the target compounds, five β-aminomalonates (1a, 1b, 2a, 2b, and 3b), one α-aminophosphonate (2c), and one nitroalkyl derivative (2h) exhibited half maximal inhibitory concentration (IC50) values in the range of 0...
June 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28641136/age-exacerbates-abnormal-protein-expression-in-a-mouse-model-of-down-syndrome
#16
Md Mahiuddin Ahmed, Aaron Block, Suhong Tong, Muriel T Davisson, Katheleen J Gardiner
The Ts65Dn is a popular mouse model of Down syndrome (DS). It displays DS-relevant features of learning/memory deficits and age-related loss of functional markers in basal forebrain cholinergic neurons. Here we describe protein expression abnormalities in brain regions of 12-month-old male Ts65Dn mice. We show that the magnitudes of abnormalities of human chromosome 21 and non-human chromosome 21 orthologous proteins are greater at 12 months than at ∼6 months. Age-related exacerbations involve the number of components affected in the mechanistic target of rapamycin pathway, the levels of components of the mitogen-activated protein kinase pathway, and proteins associated with Alzheimer's disease...
May 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28641133/abc-transporters-in-megakaryopoiesis-and-platelet-activity
#17
REVIEW
Wei Wang, Lorena Buitrago, Ying Wang
ATP-binding cassette (ABC) is a family of transporters that facilitates the translocation of substrates across cell membrane using its ATPase subunit. These transporters have key roles in multidrug resistance, lipid homeostasis, antigen processing, immunity, cell proliferation and hematopoiesis. Some ABC transporters are selectively expressed on megakaryocyte progenitor, megakaryocyte and its cellular fragment platelet. However, the role of ABC transporters in hemostasis and thrombosis were not well explored until recently...
June 14, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28641121/is-inhibitory-control-involved-in-discriminating-pseudowords-that-contain-the-reversible-letters-b-and-d
#18
Lorie-Marlène Brault Foisy, Emmanuel Ahr, Steve Masson, Olivier Houdé, Grégoire Borst
Children tend to confuse reversible letters such as b and d when they start learning to read. According to some authors, mirror errors are a consequence of the mirror generalization (MG) process that allows one to recognize objects independently of their left-right orientation. Although MG is advantageous for the visual recognition of objects, it is detrimental for the visual recognition of reversible letters. Previous studies comparing novice and expert readers demonstrated that MG must be inhibited to discriminate reversible single letters...
June 19, 2017: Journal of Experimental Child Psychology
https://www.readbyqxmd.com/read/28641106/antisense-oligonucleotides-translation-from-mouse-models-to-human-neurodegenerative-diseases
#19
REVIEW
Kathleen M Schoch, Timothy M Miller
Multiple neurodegenerative diseases are characterized by single-protein dysfunction and aggregation. Treatment strategies for these diseases have often targeted downstream pathways to ameliorate consequences of protein dysfunction; however, targeting the source of that dysfunction, the affected protein itself, seems most judicious to achieve a highly effective therapeutic outcome. Antisense oligonucleotides (ASOs) are small sequences of DNA able to target RNA transcripts, resulting in reduced or modified protein expression...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28641103/staring-at-the-clock-face-in-drosophila
#20
Ezio Rosato, Charalambos P Kyriacou
Liang et al. (2017) demonstrate how neuropeptides from two groups of clock cells appear to be responsible for the fly's circadian neurons becoming active at different times of day. By delaying the activity of their clock cell targets, they give rise to morning and evening behavior.
June 21, 2017: Neuron
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