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https://www.readbyqxmd.com/read/29208888/polyarthritis-is-a-rare-manifestation-of-pachydermoperiostosis-a-case-report
#1
M F Ahmmed, M N Shazzad, S Ferdous, A K Azad, S A Haq
Pachydermoperiostosis or primary hypertrophic osteoarthropathy, also known as Touraine-Solente-Gole syndrome, is a rare process, frequently inherited. In its complete form it is characterized by pachydermia (thickening of the skin), skeletal changes (periostosis) and acropachia (digital clubbing). Diagnosis can be made considering the typical clinical features and the histological feature. We report a patient of 25-year old man presented with joint pain involving in multiple joints for last 7 years and progressive enlargement of his hands and feet with profuse sweating of palms and soles for last 4 years...
October 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/29178640/expanding-the-mutational-spectrum-in-johanson-blizzard-syndrome-identification-of-whole-exon-deletions-and-duplications-in-the-ubr1-gene-by-multiplex-ligation-dependent-probe-amplification-analysis
#2
Maja Sukalo, Eva Schäflein, Ina Schanze, David B Everman, Nima Rezaei, Jesús Argente, Isabel Lorda-Sanchez, Charu Deshpande, Tsutomu Takahashi, Alexander Kleger, Martin Zenker
BACKGROUND: Johanson-Blizzard syndrome (JBS, MIM #243800) is a very rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, nasal wing hypoplasia, hypodontia, and other abnormalities. JBS is caused by mutations of the UBR1 gene (MIM *605981), encoding a ubiquitin ligase of the N-end rule pathway. METHODS: Molecular findings in a total of 65 unrelated patients with a clinical diagnosis of JBS who were previously screened for UBR1 mutations by Sanger sequencing were reviewed and cases lacking a disease-causing UBR1 mutation on either one or both alleles were included in this study...
November 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/29170951/bacterial-genome-editing-strategy-for-control-of-transcription-and-protein-stability
#3
Ida Lauritsen, Virginia Martínez, Carlotta Ronda, Alex Toftgaard Nielsen, Morten H H Nørholm
In molecular biology and cell factory engineering, tools that enable control of protein production and stability are highly important. Here, we describe protocols for tagging genes in Escherichia coli allowing for inducible degradation and transcriptional control of any soluble protein of interest. The underlying molecular biology is based on the two cross-kingdom tools CRISPRi and the N-end rule for protein degradation. Genome editing is performed with the CRMAGE technology and randomization of the translational initiation region minimizes the polar effects of tag insertion...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29168982/n-terminomics-reveals-control-of-arabidopsis-seed-storage-proteins-and-proteases-by-the-arg-n-end-rule-pathway
#4
Hongtao Zhang, Lucy Gannon, Kirsty L Hassall, Michael J Deery, Daniel J Gibbs, Michael J Holdsworth, Renier A L van der Hoorn, Kathryn S Lilley, Frederica L Theodoulou
The N-end rule pathway of targeted protein degradation is an important regulator of diverse processes in plants but detailed knowledge regarding its influence on the proteome is lacking. To investigate the impact of the Arg/N-end rule pathway on the proteome of etiolated seedlings, we used terminal amine isotopic labelling of substrates with tandem mass tags (TMT-TAILS) for relative quantification of N-terminal peptides in prt6, an Arabidopsis thaliana N-end rule mutant lacking the E3 ligase PROTEOLYSIS6 (PRT6)...
November 23, 2017: New Phytologist
https://www.readbyqxmd.com/read/29136445/effect-of-varying-doses-of-epicutaneous-immunotherapy-vs-placebo-on-reaction-to-peanut-protein-exposure-among-patients-with-peanut-sensitivity-a-randomized-clinical-trial
#5
Hugh A Sampson, Wayne G Shreffler, William H Yang, Gordon L Sussman, Terri F Brown-Whitehorn, Kari C Nadeau, Amarjit S Cheema, Stephanie A Leonard, Jacqueline A Pongracic, Christine Sauvage-Delebarre, Amal H Assa'ad, Frederic de Blay, J Andrew Bird, Stephen A Tilles, Franck Boralevi, Thierry Bourrier, Jacques Hébert, Todd D Green, Roy Gerth van Wijk, André C Knulst, Gisèle Kanny, Lynda C Schneider, Marek L Kowalski, Christophe Dupont
Importance: Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in preclinical and early human trials. Objective: To determine the optimal dose, adverse events (AEs), and efficacy of a peanut patch for peanut allergy treatment. Design, Setting, and Participants: Phase 2b double-blind, placebo-controlled, dose-ranging trial of a peanut patch in peanut-allergic patients (6-55 years) from 22 centers, with a 2-year, open-label extension (July 31, 2012-July 31, 2014; extension completed September 29, 2016)...
November 14, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29122887/a-reference-based-protein-degradation-assay-without-global-translation-inhibitors
#6
Jang-Hyun Oh, Shun-Jia Chen, Alexander Varshavsky
Although it is widely appreciated that the use of global translation inhibitors, such as cycloheximide, in protein degradation assays may result in artefacts, these inhibitors continue to be employed, owing to the absence of robust alternatives. We describe here the promoter reference technique (PRT), an assay for protein degradation with two advantageous features: a reference protein and a gene-specific inhibition of translation. In PRT assays, one measures, during a chase, the ratio of a test protein to a long-lived reference protein, a dihydrofolate reductase (DHFR)...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29107562/dolutegravir-as-maintenance-monotherapy-for-hiv-domono-a-phase-2-randomised-non-inferiority-trial
#7
Ingeborg Wijting, Casper Rokx, Charles Boucher, Jeroen van Kampen, Suzan Pas, Theodora de Vries-Sluijs, Carolina Schurink, Hannelore Bax, Maarten Derksen, Eleni-Rosalina Andrinopoulou, Marchina van der Ende, Eric van Gorp, Jan Nouwen, Annelies Verbon, Wouter Bierman, Bart Rijnders
BACKGROUND: The high genetic barrier to resistance of dolutegravir might allow for its use as maintenance monotherapy in patients with HIV. We investigated whether dolutegravir monotherapy was non-inferior to combination antiretroviral therapy (ART) for maintaining virological suppression in patients with HIV-1 infection successfully treated with combination ART. METHODS: We did this open-label, phase 2, randomised non-inferiority trial at two medical centres in the Netherlands...
October 26, 2017: Lancet HIV
https://www.readbyqxmd.com/read/29097074/a-phase-ii-toxicity-end-point-trial-icorg-99-09-of-accelerated-dose-escalated-hypofractionated-radiation-in-non-small-cell-lung-cancer
#8
D N Cagney, P G Thirion, M T Dunne, C Fleming, D Fitzpatrick, C M O'Shea, M A Finn, S O'Sullivan, C Booth, C D Collins, S J Buckney, A Shannon, J G Armstrong
AIMS: The objective of this phase II clinical trial was to prospectively evaluate the safety and efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy (3DCRT) in localised non-resectable/non-operable non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Sixty patients with stage I-III NSCLC were enrolled in a prospective single-arm All Ireland Co-operative Oncology Research Group (ICORG 99-09) toxicity end point phase II trial...
October 30, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/29071084/are-within-person-numerical-rating-scale-nrs-ratings-of-breathlessness-on-average-valid-in-advanced-disease-for-patients-and-for-patients-informal-carers
#9
Joshua Wade, Silvia Mendonca, Sara Booth, Gail Ewing, A Carole Gardener, Morag Farquhar
INTRODUCTION: The Numerical Rating Scale (NRS) is frequently used to assess patient-reported breathlessness in both a research and clinical context. A subgroup of patients report average breathlessness as worse than their worst breathlessness in the last 24 hours (paradoxical average). The Peak/End rule describes how the most extreme and current breathlessness influence reported average. This study seeks to highlight the existence of a subpopulation who give 'paradoxical averages using the NRS, to characterise this group and to investigate the explanatory relevance of the 'Peak/End' rule...
2017: BMJ Open Respiratory Research
https://www.readbyqxmd.com/read/29039828/-clinical-laboratory-and-instrumental-criteria-for-myocarditis-established-in-comparison-with-myocardial-biopsy-a-non-invasive-diagnostic-algorithm
#10
O V Blagova, Yu V Osipova, A V Nedostup, E A Kogan, V A Sulimov
AIM: To determine the diagnostic value of different clinical, laboratory, and instrumental signs in the diagnosis of myocarditis in patients with the picture of idiopathic arrhythmias, dilated cardiomyopathy (DCM) and in a comparison group when comparing with myocardial morphological examination. SUBJECTS AND METHODS: A study group included 100 patients (35 women; mean age, 44.7±12.5 years) with idiopathic arrhythmias (n=20) and DCM as a syndrome (n=100). All underwent myocardial morphological examination: endomyocardial biopsy (EMB) (n=71), intraoperative biopsy (n=13), study of the explanted heart (n=6), and autopsy (n=11)...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/29033328/the-cys-arg-n-end-rule-pathway-is-a-general-sensor-of-abiotic-stress-in-flowering-plants
#11
Jorge Vicente, Guillermina M Mendiondo, Mahsa Movahedi, Marta Peirats-Llobet, Yu-Ting Juan, Yu-Yen Shen, Charlene Dambire, Katherine Smart, Pedro L Rodriguez, Yee-Yung Charng, Julie E Gray, Michael J Holdsworth
Abiotic stresses impact negatively on plant growth, profoundly affecting yield and quality of crops. Although much is known about plant responses, very little is understood at the molecular level about the initial sensing of environmental stress. In plants, hypoxia (low oxygen, which occurs during flooding) is directly sensed by the Cys-Arg/N-end rule pathway of ubiquitin-mediated proteolysis, through oxygen-dependent degradation of group VII Ethylene Response Factor transcription factors (ERFVIIs) via amino-terminal (Nt-) cysteine [1, 2]...
October 23, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29033021/-smoking-cessation-and-pregnancy
#12
M Underner, O Pourrat, J Perriot, G Peiffer, N Jaafari
Active and passive smoking during pregnancy induce several deleterious effects that may have a negative impact on pregnancy progress, fetus development and both mother and newborn health. Smoking cessation should be a rule for any woman as soon as the beginning of her pregnancy, or better in anticipation of a pregnancy when contraception is no more taken. Every caregiver must help every pregnant woman who smokes to quit smoking. Smoking cessation interventions in pregnant women must combine a psychological support (mainly with cognitive behavioral therapy) and nicotine replacement therapy, which can also be used during breast feeding...
October 9, 2017: Gynecologie, Obstetrique, Fertilite & Senologie
https://www.readbyqxmd.com/read/28981713/crispr-cas9-based-genome-editing-for-simultaneous-interference-with-gene-expression-and-protein-stability
#13
Virginia Martínez, Ida Lauritsen, Tonja Hobel, Songyuan Li, Alex Toftgaard Nielsen, Morten H H Nørholm
Interference with genes is the foundation of reverse genetics and is key to manipulation of living cells for biomedical and biotechnological applications. However, classical genetic knockout and transcriptional knockdown technologies have different drawbacks and offer no control over existing protein levels. Here, we describe an efficient genome editing approach that affects specific protein abundances by changing the rates of both RNA synthesis and protein degradation, based on the two cross-kingdom control mechanisms CRISPRi and the N-end rule for protein stability...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28949872/online-public-reactions-to-fmri-communication-with-patients-with-disorders-of-consciousness-quality-of-life-end-of-life-decision-making-and-concerns-with-misdiagnosis
#14
Jennifer A Chandler, Jeffrey A Sun, Eric Racine
BACKGROUND: Recently, the news media have reported on the discovery of covert awareness and the establishment of limited communication using a functional magnetic resonance imaging (fMRI) neuroimaging technique with several brain-injured patients thought to have been in a vegetative state. This discovery has raised many ethical, legal, and social questions related to quality of life, end-of-life decision making, diagnostic and prognostic accuracy in disorders of consciousness, resource allocation, and other issues...
January 2017: AJOB Empirical Bioethics
https://www.readbyqxmd.com/read/28936674/conditional-modulation-of-biological-processes-by-low-temperature-degrons
#15
Nico Dissmeyer
Conditional modulation of biological processes plays key roles in basic and applied research and in translation. It can be achieved on various levels via a multitude of approaches. One of the directions is manipulating target protein levels and activity by transcriptional, posttranscriptional, translational, and posttranslational control. Because in most of these techniques, the synthesis of the target proteins is adjusted to the needs, they all rely on the specific half-life of the target protein and its turn-over...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28931440/core-outcomes-in-periodontal-trials-study-protocol-for-core-outcome-set-development
#16
Thomas J Lamont, Jan E Clarkson, David N J Ricketts, Peter A Heasman, Craig R Ramsay
BACKGROUND: There are a large number of clinical outcome measures used to assess the effectiveness of prevention and management strategies of periodontal diseases. This heterogeneity causes difficulties when trying to synthesise data for systematic reviews or clinical guidelines, reducing their impact. Core outcome sets are an agreed, standardised list of outcomes that should be measured and reported in all trials in specific clinical areas. We aim to develop a core outcome set for effectiveness trials investigating the prevention and management of periodontal disease in primary or secondary care...
September 20, 2017: Trials
https://www.readbyqxmd.com/read/28906386/development-and-validation-of-a-prediction-score-system-in-lupus-nephritis
#17
Yi Tang, Wei Qin, Wei Peng, Ye Tao
The risk assessment for developing end-stage renal disease (ESRD) remains unclear in patients with lupus nephritis (LN). The purpose of this study was to develop and validate a prediction rule for estimating the individual risk of ESRD in patients with LN using clinical and pathological data.A total of 599 patients with LN diagnosed by renal biopsy between June 2009 and June 2014 in West China Hospital of Sichuan University were retrospectively followed. Patients were randomly divided into derivation cohort (n = 379) and validation cohort (n = 220)...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28760210/a-randomized-trial-of-a-1-hour-troponin-t-protocol-in-suspected-acute-coronary-syndromes-design-of-the-rapid-assessment-of-possible-acs-in-the-emergency-department-with-high-sensitivity-troponin-t-rapid-tnt-study
#18
RANDOMIZED CONTROLLED TRIAL
Cynthia Papendick, Andrew Blyth, Anil Seshadri, Michael J R Edmonds, Tom Briffa, Louise Cullen, Stephen Quinn, Jon Karnon, Anthony Chuang, Adam J Nelson, Matthew Horsfall, Erin Morton, Derek P Chew
BACKGROUND: Protocols incorporating high-sensitivity troponin to guide decision making in the disposition of patients with suspected acute coronary syndromes (ACS) in the emergency department have received a lot of attention. Traditionally, patients with chest pain have required long periods of observation in emergency department before being deemed safe for discharge. In an era of limited health service resources, a protocol that could discharge patients safely within an hour of presentation is extremely attractive...
August 2017: American Heart Journal
https://www.readbyqxmd.com/read/28741696/age-dependent-regulation-of-erf-vii-transcription-factor-activity-in-arabidopsis-thaliana
#19
Beatrice Giuntoli, Vinay Shukla, Federica Maggiorelli, Federico M Giorgi, Lara Lombardi, Pierdomenico Perata, Francesco Licausi
The Group VII Ethylene Responsive Factors (ERFs-VII) RAP2.2 and RAP2.12 have been mainly characterized with regard to their contribution as activators of fermentation in plants. However, transcriptional changes measured in conditions that stabilize these transcription factors exceed the mere activation of this biochemical pathway, implying additional roles performed by the ERF-VIIs in other processes. We evaluated gene expression in transgenic Arabidopsis lines expressing a stabilized form of RAP2.12, or hampered in ERF-VII activity, and identified genes affected by this transcriptional regulator and its homologs, including some involved in oxidative stress response, which are not universally induced under anaerobic conditions...
October 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28740232/p62-sqstm1-sequestosome-1-is-an-n-recognin-of-the-n-end-rule-pathway-which-modulates-autophagosome-biogenesis
#20
Hyunjoo Cha-Molstad, Ji Eun Yu, Zhiwei Feng, Su Hyun Lee, Jung Gi Kim, Peng Yang, Bitnara Han, Ki Woon Sung, Young Dong Yoo, Joonsung Hwang, Terry McGuire, Sang Mi Shim, Hyun Dong Song, Srinivasrao Ganipisetti, Nuozhou Wang, Jun Min Jang, Min Jae Lee, Seung Jun Kim, Kyung Ho Lee, Jin Tae Hong, Aaron Ciechanover, Inhee Mook-Jung, Kwang Pyo Kim, Xiang-Qun Xie, Yong Tae Kwon, Bo Yeon Kim
Macroautophagy mediates the selective degradation of proteins and non-proteinaceous cellular constituents. Here, we show that the N-end rule pathway modulates macroautophagy. In this mechanism, the autophagic adapter p62/SQSTM1/Sequestosome-1 is an N-recognin that binds type-1 and type-2 N-terminal degrons (N-degrons), including arginine (Nt-Arg). Both types of N-degrons bind its ZZ domain. By employing three-dimensional modeling, we developed synthetic ligands to p62 ZZ domain. The binding of Nt-Arg and synthetic ligands to ZZ domain facilitates disulfide bond-linked aggregation of p62 and p62 interaction with LC3, leading to the delivery of p62 and its cargoes to the autophagosome...
July 24, 2017: Nature Communications
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