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https://www.readbyqxmd.com/read/29234112/a-switch-in-nucleotide-affinity-governs-activation-of-the-src-and-tec-family-kinases
#1
Freia von Raußendorf, Anita de Ruiter, Thomas A Leonard
The Tec kinases, closely related to Src family kinases, are essential for lymphocyte function in the adaptive immune system. Whilst the Src and Abl kinases are regulated by tail phosphorylation and N-terminal myristoylation respectively, the Tec kinases are notable for the absence of either regulatory element. We have found that the inactive conformations of the Tec kinase Itk and Src preferentially bind ADP over ATP, stabilising both proteins. We demonstrate that Itk adopts the same conformation as Src and that the autoinhibited conformation of Src is independent of its C-terminal tail...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233700/volumetric-analysis-of-keratocystic-odontogenic-tumors-and-non-neoplastic-jaw-cysts-comparison-and-its-clinical-relevance
#2
Martin Kauke, Ali-Farid Safi, Andrea Grandoch, Hans-Joachim Nickenig, Joachim Zöller, Matthias Kreppel
The keratocystic odontogenic tumor (KCOT) is capable of causing vast osseous destruction. Histopathological examination is pivotal for diagnosis. The diagnostic process can sometimes be hindered by tissue inflammation of KCOTs with loss of defining criteria, resulting in misdiagnosis as an odontogenic jaw cyst. We discuss the possible merits of volumetric analysis when facing this particular diagnostic dilemma and for pathophysiological characterization of KCOTs. We included 114 patients, of whom 27 were histopathologically diagnosed with a KCOT and 87 with dentigerous (n = 41) and periapical cyst (n = 46)...
November 21, 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/29215439/age-related-volumetric-changes-in-mandibular-condyles
#3
Ali-Farid Safi, Martin Kauke, Andrea Grandoch, Hans-Joachim Nickenig, Joachim E Zöller, Matthias Kreppel
A precise knowledge of the condylar changes with advancing age may improve understanding of pathophysiological alterations of the mandibular condyles. However, the majority of studies focusses on morphological changes, although volumetric analysis based upon cone beam computerized tomography may provide important additional data to characterize mandibular condyles. Therefore, we aimed to provide and compare volumetric data of mandibular condyles of a young and old patient group. This is a retrospective chart review of 195 patients with cone beam computerized tomography between 2007 and 2016...
December 6, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/29215437/volumetric-analysis-of-700-mandibular-condyles-based-upon-cone-beam-computed-tomography
#4
Ali-Farid Safi, Martin Kauke, Andrea Grandoch, Hans-Joachim Nickenig, Joachim E Zöller, Matthias Kreppel
The authors' aim was to provide volumetric data of mandibular condyles based upon cone beam computed tomography with the means of semiautomatic segmentation.Retrospective chart review of 350 patients (700 mandibular condyles) with cone beam computerized tomography between February 2007 and December 2016. Univariate analysis was performed to analyze associations between variables. P values <0.05 were considered significant. Volume measurement was performed in a semiautomatic segmentation method with the program "ITK-Snap...
December 6, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/29199677/effect-of-tyrosine-kinase-inhibitors-on-the-glucose-levels-in-diabetic-and-nondiabetic-patients
#5
E Y Romero-Ventosa, L Otero-Millán, S González-Costas, P Vilasoa-Boo, A Silva-López, C Arroyo-Conde, G Piñeiro-Corrales
CONTEXT: Tyrosine kinase inhibitors (TKIs) are used in different types of cancers due to their good profile of adverse reactions and their convenience in the oral administration. Some studies describe that certain TKIs are associated with changes in the glycemic profile of the patients. AIMS: This study aims to determine if treatment with ITK affects to serum glucose levels in clinical practice. SETTINGS AND DESIGN: A retrospective study was carried out in 136 episodes (112 patients treated with sorafenib, sunitinib, imatinib, dasatinib, or nilotinib)...
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29129717/a-chemoproteomic-approach-to-query-the-degradable-kinome-using-a-multi-kinase-degrader
#6
Hai-Tsang Huang, Dennis Dobrovolsky, Joshiawa Paulk, Guang Yang, Ellen L Weisberg, Zainab M Doctor, Dennis L Buckley, Joong-Heui Cho, Eunhwa Ko, Jaebong Jang, Kun Shi, Hwan Geun Choi, James D Griffin, Ying Li, Steven P Treon, Eric S Fischer, James E Bradner, Li Tan, Nathanael S Gray
Heterobifunctional molecules that recruit E3 ubiquitin ligases, such as cereblon, for targeted protein degradation represent an emerging pharmacological strategy. A major unanswered question is how generally applicable this strategy is to all protein targets. In this study, we designed a multi-kinase degrader by conjugating a highly promiscuous kinase inhibitor with a cereblon-binding ligand, and used quantitative proteomics to discover 28 kinases, including BTK, PTK2, PTK2B, FLT3, AURKA, AURKB, TEC, ULK1, ITK, and nine members of the CDK family, as degradable...
November 7, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29129599/itk-and-rlk-inhibitor-prn694-improves-skin-disease-in-two-mouse-models-of-psoriasis
#7
Jessica M Fuhriman, Mårten C G Winge, Helena Haberstock-Debic, Jens Oliver Funk, J Michael Bradshaw, M Peter Marinkovich
The chronic and highly prevalent skin disorder psoriasis vulgaris is characterized by a hyperproliferative epidermis and aberrant immune activity. Many studies have highlighted the role of differentiated T lymphocytes in psoriasis progression. Several biologics are currently available that target pro-inflammatory cytokines produced by T-lymphocytes, but the need for improved therapies persists. The small molecule PRN694 covalently binds ITK and RLK, two TEC kinases activated downstream of T lymphocyte activation, both of which are upregulated in psoriatic skin...
November 9, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29103834/changes-in-condylar-volume-and-joint-spaces-after-orthognathic-surgery
#8
R J da Silva, C V Valadares Souza, G A Souza, G M B Ambrosano, D Q Freitas, E Sant'Ana, C de Oliveira-Santos
The aim of this study was to evaluate the changes in condylar volume and joint spaces occurring in patients undergoing bimaxillary orthognathic surgery for the treatment of class II deformities, by means of cone beam computed tomography (CBCT). Initial and follow-up (at least 6 months) CBCT examinations of 114 condyles (57 patients) were studied retrospectively. Linear measurements of the joint space and volumetric analysis of changes in condylar volume were performed using Dolphin 3D Imaging in association with ITK-SNAP 3...
November 2, 2017: International Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/29045421/enlarged-virchow-robin-spaces-associate-with-cognitive-decline-in-multiple-sclerosis
#9
Alice Favaretto, Andrea Lazzarotto, Alice Riccardi, Stefano Pravato, Monica Margoni, Francesco Causin, Maria Giulia Anglani, Dario Seppi, Davide Poggiali, Paolo Gallo
The clinical significance of Virchow Robin spaces (VRS) in inflammatory brain disorders, especially in multiple sclerosis (MS), is still undefined. We analysed enlarged VRS (eVRS) by means of phase sensitive inversion recovery (PSIR) MRI sequence and investigated their association with inflammation or brain atrophy, and to clinical or physical disability. Forty-three MS patients (21 clinically isolated syndrome suggestive of MS [CIS], 15 RRMS, 7 progressive [PMS]) and 10 healthy controls (HC) were studied. 3DT1, 3DFLAIR and 2DPSIR images were obtained with a 3T MRI scanner...
2017: PloS One
https://www.readbyqxmd.com/read/29018633/a-software-tool-for-heart-avj-motion-tracking-using-cine-cardiovascular-magnetic-resonance-images
#10
Pengdong Xiao, Xiaodan Zhao, Shuang Leng, Ru San Tan, Philip Wong, Liang Zhong
One important index to assess left ventricular diastolic function is the quantitative measurement of atrioventricular junction (AVJ) motion in one cardiac cycle including systole and diastole. The best way to perform the measurement is to use a software tool that can conduct AVJ motion tracking from cine cardiovascular magnetic resonance (CMR) images. In this paper, a software tool for this purpose is presented by using the insight segmentation and registration toolkit (ITK), the visualization toolkit (VTK), and Qt...
2017: IEEE Journal of Translational Engineering in Health and Medicine
https://www.readbyqxmd.com/read/28972087/correction-t-cell-receptor-signaling-activates-an-itk-nf-%C3%AE%C2%BAb-gata-3-axis-in-t-cell-lymphomas-facilitating-resistance-to-chemotherapy
#11
(no author information available yet)
No abstract text is available yet for this article.
October 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28882879/acalabrutinib-acp-196-a-covalent-bruton-tyrosine-kinase-inhibitor-with-a-differentiated-selectivity-and-in-vivo-potency-profile
#12
Tjeerd Barf, Todd Covey, Raquel Izumi, Bas van de Kar, Michael Gulrajani, Bart van Lith, Maaike van Hoek, Edwin de Zwart, Diana Mittag, Dennis Demont, Saskia Verkaik, Fanny Krantz, Paul G Pearson, Roger Ulrich, Allard Kaptein
Several small-molecule Bruton tyrosine kinase (BTK) inhibitors are in development for B cell malignancies and autoimmune disorders, each characterized by distinct potency and selectivity patterns. Herein we describe the pharmacologic characterization of BTK inhibitor acalabrutinib [compound 1, ACP-196 (4-[8-amino-3-[(2S)-1-but-2-ynoylpyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-N-(2-pyridyl)benzamide)]. Acalabrutinib possesses a reactive butynamide group that binds covalently to Cys481 in BTK. Relative to the other BTK inhibitors described here, the reduced intrinsic reactivity of acalabrutinib helps to limit inhibition of off-target kinases having cysteine-mediated covalent binding potential...
November 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28735346/anatomical-relation-between-nasal-septum-deviation-and-oropharynx-volume-in-different-facial-patterns-evaluated-through-cone-beam-computed-tomography
#13
Ana Márcia Viana Wanzeler, Maria Daniela Oliveira Renda, Maria Eduarda de Oliveira Pereira, Sérgio Melo Alves-Junior, Fabricio Mesquita Tuji
INTRODUCTION: The objective of this study was to establish the anatomical relation between nasal septum deviation (NSD) and oropharynx volume in different facial patterns using cone beam computed tomography (CBCT). METHODS: Ninety CBCT examinations were analyzed. InVivoDental software was used to evaluate cephalometric image reconstructions in terms of facial type, determined from cephalometric measurements indicative of growth direction; the presence of NSD was also evaluated...
July 22, 2017: Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28715317/itk-snap-an-intractive-medical-image-segmentation-tool-to-meet-the-need-for-expert-guided-segmentation-of-complex-medical-images
#14
Paul A Yushkevich, Guido Gerig
Imaging is a crucial tool in medicine and biomedical research. Magnetic resonance imaging (MRI), computational tomography (CT), proton emission tomography (PET), and ultrasound are routinely used not only to diagnose disease but also to plan and guide surgical interventions, track disease progression, measure the response of the body to treatment, and understand how genetic and environmental factors relate to anatomical and functional phenotypes.
July 2017: IEEE Pulse
https://www.readbyqxmd.com/read/28714866/ibrutinib-treatment-improves-t-cell-number-and-function-in-cll-patients
#15
MULTICENTER STUDY
Meixiao Long, Kyle Beckwith, Priscilla Do, Bethany L Mundy, Amber Gordon, Amy M Lehman, Kami J Maddocks, Carolyn Cheney, Jeffrey A Jones, Joseph M Flynn, Leslie A Andritsos, Farrukh Awan, Joseph A Fraietta, Carl H June, Marcela V Maus, Jennifer A Woyach, Michael A Caligiuri, Amy J Johnson, Natarajan Muthusamy, John C Byrd
BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28713426/3d-morphology-analysis-of-tmj-articular-eminence-in-magnetic-resonance-imaging
#16
Izabella Nascimento Falcão, Maria Beatriz Carrazzone Cal Alonso, Lucas Hian da Silva, Sérgio Lúcio Pereira de Castro Lopes, Lívia Pichi Comar, André Luiz Ferreira Costa
PURPOSE: The objective of this study was to evaluate the computational reconstruction of the articular eminence of the temporomandibular joint (TMJ) based on magnetic resonance imaging (MRI) and semiautomatic volumetric segmentation techniques for morphological classification of the TMJ structure. MATERIALS AND METHODS: A total of 36 MRI scans of TMJ individuals were selected and formatted by using the ITK-SNAP software, consisting of MRI segmentation and generation of 3D models...
2017: International Journal of Dentistry
https://www.readbyqxmd.com/read/28706781/assessment-of-condyle-masseter-and-temporal-muscles-volumes-in-patients-with-juvenile-systemic-lupus-erythematosus-a-cross-sectional-study
#17
Sandra Lucia Golin, Nailu Angélica Sinicato, Karyna Valle-Corotti, Acácio Fuziy, Ana Carla Nahas-Scocate, Simone Appenzeller, Andre Luiz Ferreira Costa
AIMS: The purpose of this study was to evaluate the effect of the corticosteroid therapy for both treatment of juvenile systemic lupus erythematosus and disease activity on two masticatory muscles and condyle of the temporomandibular joint. METHODS: A total of 21 controls and 48 juvenile systemic lupus erythematosus patients were investigated. Volumes of the temporal and masseter muscles and condyle of the subjects were assessed by using a 3D reconstruction in magnetic resonance imaging...
May 2017: Journal of Oral Biology and Craniofacial Research
https://www.readbyqxmd.com/read/28703583/consensx-webserver-for-the-analysis-of-protein-structural-ensembles-reflecting-experimentally-determined-internal-dynamics
#18
Dániel Dudola, Bertalan Kovács, Zoltán Gáspári
Ensemble-based models of protein structure and dynamics reflecting experimental parameters are increasingly used to obtain deeper understanding of the role of dynamics in protein function. Such ensembles differ substantially from those routinely deposited in the PDB and, consequently, require specialized validation and analysis methodology. Here we describe our completely rewritten online validation tool, CoNSEnsX(+), that offers a standardized way to assess the correspondence of such ensembles to experimental NMR parameters...
August 28, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28664871/influence-of-tio2-and-si-on-the-exciton-phonon-interaction-in-pbi2-and-cds-semiconductors-evidenced-by-raman-spectroscopy
#19
A Nila, I Baltog, D Dragoman, M Baibarac, I Mercioniu
The exciton-phonon interaction, considered as a stimulated Raman scattering process, is studied in different semiconductor mixtures: PbI2/TiO2, PbI2/Si and CdS/Si. Raman spectra recorded at excitation wavelengths of 514.5 and 488 nm for PbI2 and CdS, respectively, reveal a strong enhancement of the Raman lines peaked at 97 and 305 cm(-1), evaluated by the ratio I TK/I 300 K between the relative intensities of the spectra recorded in the temperature range of 88-300 K. It is found that PbI2 and CdS exhibit a decrease in the Raman intensity modes with decreasing temperature, while in TiO2 and Si an increase in the Raman lines intensities peaked at 138 and 520 cm(-1) is observed...
September 13, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/28644030/a-plc-%C3%AE-1-feedback-pathway-regulates-lck-substrate-phosphorylation-at-the-t-cell-receptor-and-slp-76-complex
#20
Judson Belmont, Tao Gu, Ashley Mudd, Arthur R Salomon
Phospholipase C gamma 1 (PLC-γ1) occupies a critically important position in the T-cell signaling pathway. While its functions as a regulator of both Ca(2+) signaling and PKC-family kinases are well characterized, PLC-γ1's role in the regulation of early T-cell receptor signaling events is incompletely understood. Activation of the T-cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of both positive and negative feedback pathways from SLP-76 to the apical kinase in the pathway, Lck...
August 4, 2017: Journal of Proteome Research
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