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https://www.readbyqxmd.com/read/29744390/stage-1-registered-report-variation-in-neurodevelopmental-outcomes-in-children-with-sex-chromosome-trisomies-protocol-for-a-test-of-the-double-hit-hypothesis
#1
Dianne F Newbury, Nuala H Simpson, Paul A Thompson, Dorothy V M Bishop
Background : The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. Group averages, however, obscure a wide range of outcomes. Hypothesis: The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. Neuroligin-4 genes are expressed from X and Y chromosomes; they play an important role in synaptic development and have been implicated in neurodevelopment...
2018: Wellcome Open Research
https://www.readbyqxmd.com/read/29725121/global-site-specific-analysis-of-glycoprotein-n-glycan-processing
#2
Liwei Cao, Jolene K Diedrich, Yuanhui Ma, Nianshuang Wang, Matthias Pauthner, Sung-Kyu Robin Park, Claire M Delahunty, Jason S McLellan, Dennis R Burton, John R Yates, James C Paulson
N-glycans contribute to the folding, stability and functions of the proteins they decorate. They are produced by transfer of the glycan precursor to the sequon Asn-X-Thr/Ser, followed by enzymatic trimming to a high-mannose-type core and sequential addition of monosaccharides to generate complex-type and hybrid glycans. This process, mediated by the concerted action of multiple enzymes, produces a mixture of related glycoforms at each glycosite, making analysis of glycosylation difficult. To address this analytical challenge, we developed a robust semiquantitative mass spectrometry (MS)-based method that determines the degree of glycan occupancy at each glycosite and the proportion of N-glycans processed from high-mannose type to complex type...
June 2018: Nature Protocols
https://www.readbyqxmd.com/read/29725074/understanding-the-relationship-between-the-neurologic-pupil-index-and-constriction-velocity-values
#3
Ifeoluwa Shoyombo, Venkatesh Aiyagari, Sonja E Stutzman, Folefac Atem, Michelle Hill, Stephen A Figueroa, Chad Miller, Amber Howard, DaiWai M Olson
The pupillary light reflex (PLR) describes the response when light hits the retina and sends a signal (cranial nerve II) to the Edinger-Westphal Nucleus which via cranial nerve III results in pupillary constriction. The Neurological Pupil indexTM (NPi) and pupil constriction velocity (CV) are two distinct variables that can be observed and measured using a pupillometer. We examine NPi and CV in 27,462 pupil readings (1,617 subjects). NPi values <3.0 and a CV < 0.8 mm/sec were considered abnormal...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29704602/implication-of-sulfonylurea-derivatives-as-prospective-inhibitors-of-human-carbonic-anhydrase-ii
#4
Danish Idrees, Murtuza Hadianawala, Amarjyoti Das Mahapatra, Bhaskar Datta, Sonam Roy, Shahzaib Ahamad, Parvez Khan, Md Imtiyaz Hassan
Selective carbonic anhydrase (CA) inhibitors have gained a lot of importance owing to the implication of specific isoforms of CA in certain diseases like glaucoma, leukemia, cystic fibrosis, and epilepsy. A novel class of sulfonylurea derivatives was synthesized from corresponding sulfonyl chlorides and amines. Compounds with different pendant moieties in the sulfonylurea derivatives show significant interactions with human carbonic anhydrase II (CAII). In vitro evaluation of the sulfonylurea derivatives revealed three compounds possessing admirable inhibitory activity against CAII...
April 25, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29700878/adaptation-of-evidence-based-guideline-recommendations-to-address-urinary-incontinence-in-nursing-home-residents-according-to-the-adapte-process
#5
Manuela Hoedl, Daniela Schoberer, Ruud Jg Halfens, Christa Lohrmann
AIMS AND OBJECTIVES: To adapt international guideline recommendations for the conservative management of urinary incontinence (UI), defined as any involuntary loss of urine, in Austrian nursing home residents following the ADAPTE-process. BACKGROUND: Many international guidelines for managing urinary incontinence (UI) are available. Nevertheless, the international recommendations have not yet been adapted to address the Austrian nursing home context. This crucial adaptation process will enhance the acceptance and applicability of the recommendations as well as encourage adherence among Austrian nurses and nursing home residents...
April 27, 2018: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/29697296/the-physical-profile-of-adult-male-basketball-players-differences-between-competitive-levels-and-playing-positions
#6
Davide Ferioli, Ermanno Rampinini, Andrea Bosio, Antonio La Torre, Matteo Azzolini, Aaron J Coutts
This study examined the physical differences in adult male basketball players of different competitive level and playing position using a large cohort. In the middle of the regular season, 129 players from four different Divisions completed a Yo-YoIR1 and, after 3-to-8 days, they performed a 6-min continuous running test (Mognoni's test), a counter-movement jump (CMJ) test and a 5-min High-intensity Intermittent running test (HIT). Magnitude-based inferences revealed that differences in HIT were very likely moderate between Division I and II and likely small between Division II and III...
April 26, 2018: Journal of Sports Sciences
https://www.readbyqxmd.com/read/29674523/efficient-high-throughput-screening-by-er-ca-2-measurement-to-identify-inhibitors-of-ryanodine-receptor-ca2-release-channels
#7
Takashi Murayama, Nagomi Kurebayashi, Mari Ikegami-Yuasa, Shuichi Mori, Yukina Suzuki, Ryunosuke Akima, Haruo Ogawa, Junji Suzuki, Kazunori Kanemaru, Hideto Oyamada, Yuji Kiuchi, Masamitsu Iino, Hiroyuki Kagechika, Takashi Sakurai
Genetic mutations in ryanodine receptors (RyRs), Ca2+-release channels in the sarcoplasmic reticulum essential for muscle contractions, cause various skeletal muscle and cardiac diseases. Because the main underlying mechanism of the pathogenesis is overactive Ca2+ release by gain-of-function of the RyR channel, inhibition of RyRs is expected to be a promising treatment for these diseases. Here, to identify inhibitors specific to skeletal muscle type 1 RyR (RyR1), we developed a novel high-throughput screening (HTS) platform using time-lapse fluorescence measurement of Ca2+ concentrations in the endoplasmic reticulum (ER) ([Ca2+]ER)...
April 19, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29669447/attention-in-individuals-with-aphasia-performance-on-the-conners-continuous-performance-test-2nd-edition
#8
Jaime B Lee, Masha Kocherginsky, Leora R Cherney
Studies suggest that individuals with aphasia present with impairments in attention. However, most research has been conducted with small sample sizes using experimental protocols that lack established psychometric properties. We examined the attention performance of 114 individuals with chronic post-stroke aphasia using a standardised, norm-referenced assessment of attention, the Conners' Continuous Performance Test-II (CPT-II; Conners, C. K. (2000). Conner s' Continuous Performance Test II. Toronto: Multi-Health Systems Inc)...
April 18, 2018: Neuropsychological Rehabilitation
https://www.readbyqxmd.com/read/29665337/when-is-ligand-pk-a-a-good-descriptor-for-catalyst-energetics-in-search-of-optimal-co-2-hydration-catalysts
#9
Jeong Yun Kim, Heather J Kulik
We present a detailed study of nearly 70 Zn molecular catalysts for CO2 hydration from four diverse ligand classes ranging from well-studied carbonic anhydrase mimics (e.g., cyclen) to new structures we obtain by leveraging diverse hits from large organic libraries. Using kinetic analysis and establishing linear free energy relationships, we confirm turnover to be sensitive to relative thermodynamic stability of reactive hydroxyl and bound bicarbonate moieties. We observe a wide range of thermodynamic stabilities for these intermediates, showing up to 6 kcal/mol improvement over well-studied cyclen catalysts...
April 17, 2018: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/29661748/virtual-reality-cue-refusal-video-game-for-alcohol-and-cigarette-recovery-support-summative-study
#10
Mary Metcalf, Karen Rossie, Katie Stokes, Christina Tallman, Bradley Tanner
BACKGROUND: New technologies such as virtual reality, augmented reality, and video games hold promise to support and enhance individuals in addiction treatment and recovery. Quitting or decreasing cigarette or alcohol use can lead to significant health improvements for individuals, decreasing heart disease risk and cancer risks (for both nicotine and alcohol use), among others. However, remaining in recovery from use is a significant challenge for most individuals. OBJECTIVE: We developed and assessed the Take Control game, a partially immersive Kinect for Windows platform game that allows users to counter substance cues through active movements (hitting, kicking, etc)...
April 16, 2018: JMIR Serious Games
https://www.readbyqxmd.com/read/29651456/systematic-reconstruction-of-autism-biology-from-massive-genetic-mutation-profiles
#11
Weijun Luo, Chaolin Zhang, Yong-Hui Jiang, Cory R Brouwer
Autism spectrum disorder (ASD) affects 1% of world population and has become a pressing medical and social problem worldwide. As a paradigmatic complex genetic disease, ASD has been intensively studied and thousands of gene mutations have been reported. Because these mutations rarely recur, it is difficult to (i) pinpoint the fewer disease-causing versus majority random events and (ii) replicate or verify independent studies. A coherent and systematic understanding of autism biology has not been achieved. We analyzed 3392 and 4792 autism-related mutations from two large-scale whole-exome studies across multiple resolution levels, that is, variants (single-nucleotide), genes (protein-coding unit), and pathways (molecular module)...
April 2018: Science Advances
https://www.readbyqxmd.com/read/29649767/heparin-induced-thrombocytopenia-a-critical-appraisal-of-clinical-practice-guidelines-with-the-agree-ii-instrument
#12
Ying Wang, Zhi-Kang Ye, Ji-Feng Li, Xiang-Li Cui, Li-Hong Liu
BACKGROUND: Despite the availability of clinical practice guidelines (CPGs), the risk of death or thromboembolic complication associated with heparin-induced thrombocytopenia (HIT) remains high. Our aim was to systematically review the quality of CPGs for HIT and summarize the recommendations. METHODS: CPGs for HIT were systematically searched on PubMed, Embase, guidelines' websites, and Google up to August 6, 2017. Independently, three appraisers assessed the quality of CPGs using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument and extracted the data...
March 27, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29645362/structural-plasticity-of-the-tdrd3-tudor-domain-probed-by-a-fragment-screening-hit
#13
Jiuyang Liu, Shuya Zhang, Mingqing Liu, Yaqian Liu, Gilbert Nshogoza, Jia Gao, Rongsheng Ma, Yang Yang, Jihui Wu, Jiahai Zhang, Fudong Li, Ke Ruan
As a reader of di-methylated arginine on various proteins, such as histone, RNA polymerase II, PIWI and Fragile X mental retardation protein, the Tudor domain of Tudor domain-containing protein 3 (TDRD3) mediates transcriptional activation in nucleus and formation of stress granules in the cytoplasm. Despite the TDRD3 implication in cancer cell proliferation and invasion, warheads to block the di-methylated arginine recognition pocket of the TDRD3 Tudor domain have not yet been uncovered. Here we identified 14 small molecule hits against the TDRD3 Tudor domain through NMR fragment-based screening...
April 12, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29627398/anatomical-investigations-on-intraosseous-access-in-stillborns-comparison-of-different-devices-and-techniques
#14
Zeynep Fuchs, Martin Scaal, Heinz Haverkamp, Friederike Koerber, Thorsten Persigehl, Frank Eifinger
AIM: Intraosseous (IO)-access plays an alternative route during resuscitation. Our study was performed to investigate the successful rate of IO-access in preterm and term stillborns using different devices and techniques. METHODS: The cadavers used were legal donations. 16 stillborns, median: 29.2weeks (IQR 27.2-38.4) were investigated. Two different needles (a: Butterfly needle,21G,Venofix® Fa.Braun; b: Arrow® EZ-IO® 15G, Teleflex,Dublin,Ireland) were used. Needles were inserted i: manually, using a Butterfly needle; ii: manually, using EZ-IO® needle or iii: using a battery-powered semi-automatic drill (Arrow® EZ-IO® )...
April 5, 2018: Resuscitation
https://www.readbyqxmd.com/read/29602674/design-synthesis-and-biological-evaluation-of-new-b-raf-v600e-kinase-inhibitors
#15
Peng-Fei Wang, Yong-Jiao Zhang, Dong Wang, Hui-Min Hu, Zhong-Chang Wang, Chen Xu, Han-Yue Qiu, Hai-Liang Zhu
The association of deregulated signal pathways with various diseases has long been a research hotspot. One of the most important signal pathways, the MAPK (mitogen-activated protein kinase) signal pathway, plays a vital role in transducing extracellular signals into vital intracellular mechanisms. While mutations on its key component Raf kinase lead to sever diseases, targeted inhibition has thereby become an attractive therapeutic strategy. Several drugs have been approved for the treatment of Raf relevant diseases, yet more candidates are ever needed as the known drugs have confronted resistance and side effects...
March 26, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29587795/clinical-outcome-after-particle-therapy-for-meningiomas-of-the-skull-base-toxicity-and-local-control-in-patients-treated-with-active-rasterscanning
#16
Rami A El Shafie, Maja Czech, Kerstin A Kessel, Daniel Habermehl, Dorothea Weber, Stefan Rieken, Nina Bougatf, Oliver Jäkel, Jürgen Debus, Stephanie E Combs
BACKGROUND: Meningiomas of the skull base account for 25-30% of all meningiomas. Due to the complex structure of the cranial base and its close proximity to critical structures, surgery is often associated with substantial morbidity. Treatment options include observation, aggressive surgical intervention, stereotactic or conventional radiotherapy. In this analysis we evaluate the outcome of 110 patients with meningiomas of the skull base treated with particle therapy. It was performed within the framework of the "clinical research group heavy ion therapy" and supported by the German Research Council (DFG, KFO 214)...
March 27, 2018: Radiation Oncology
https://www.readbyqxmd.com/read/29574079/new-fluorescence-based-high-throughput-screening-assay-for-small-molecule-inhibitors-of-tyrosyl-dna-phosphodiesterase-2-tdp2
#17
Carlos J A Ribeiro, Jayakanth Kankanala, Ke Shi, Kayo Kurahashi, Evgeny Kiselev, Azhar Ravji, Yves Pommier, Hideki Aihara, Zhengqiang Wang
Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase II (TOP2) mediated DNA damages and causes resistance to TOP2-targeted cancer therapy. Inhibiting TDP2 could sensitize cancer cells toward TOP2 inhibitors. However, potent TDP2 inhibitors with favorable physicochemical properties are not yet reported. Therefore, there is a need to search for novel molecular scaffolds capable of inhibiting TDP2. We report herein a new simple, robust, homogenous mix-and-read fluorescence biochemical assay based using humanized zebrafish TDP2 (14M_zTDP2), which provides biochemical and molecular structure basis for TDP2 inhibitor discovery...
March 21, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29565326/curcuminoids-as-ebv-lytic-activators-for-adjuvant-treatment-in-ebv-positive-carcinomas
#18
Octavia Ramayanti, Mitch Brinkkemper, Sandra A W M Verkuijlen, Leni Ritmaleni, Mei Lin Go, Jaap M Middeldorp
Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase and antiviral valganciclovir to enhance cell death and prevent virus production. CLVA treatment has proven safe in phase-I/II trials with promising clinical responses in patients with recurrent NPC. However, a major challenge is to maximize EBV lytic reactivation by CLVA...
March 22, 2018: Cancers
https://www.readbyqxmd.com/read/29555939/integrated-modelling-of-cell-responses-after-irradiation-for-dna-targeted-effects-and-non-targeted-effects
#19
Yusuke Matsuya, Kohei Sasaki, Yuji Yoshii, Go Okuyama, Hiroyuki Date
Intercellular communication after ionizing radiation exposure, so-called non-targeted effects (NTEs), reduces cell survival. Here we describe an integrated cell-killing model considering NTEs and DNA damage along radiation particle tracks, known as DNA-targeted effects (TEs) based on repair kinetics of DNA damage. The proposed model was applied to a series of experimental data, i.e., signal concentration, DNA damage kinetics, cell survival curve and medium transfer bystander effects (MTBEs). To reproduce the experimental data, the model considers the following assumptions: (i) the linear-quadratic (LQ) function as absorbed dose to express the hit probability to emit cell-killing signals, (ii) the potentially repair of DNA lesions induced by NTEs, and (iii) lower efficiency of repair for the damage in NTEs than that in TEs...
March 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29537924/fragment-screening-of-human-kynurenine-aminotransferase-ii
#20
Gayan S Jayawickrama, Alireza Nematollahi, Guanchen Sun, W Bret Church
Kynurenine aminotransferase-II (KAT-II) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that acts in the tryptophan metabolic pathway by catalyzing the transamination of kynurenine into kynurenic acid (KYNA). It is one of four isoforms in the KAT family, of which it is the primary homologue responsible for KYNA production in the mammalian brain. KAT-II is targeted for inhibition as KYNA is implicated in diseases such as schizophrenia, where it is found in elevated concentrations. Previously, many different approaches have been taken to develop KAT-II inhibitors, and herein fragment-based drug design (FBDD) approaches have been exploited to provide further lead compounds that can be designed into novel inhibitors...
March 1, 2018: SLAS Discovery
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