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Jingjing Wu, Mingzhi Zhang, Delong Liu
The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been approved for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Acquired resistance to ibrutinib due to BTK C481S mutation has been reported. Mutations in PLCγ2 can also mediate resistance to ibrutinib. Untoward effects due to off-target effects are also disadvantages of ibrutinib. More selective and potent BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being investigated. This review summarized the preclinical research and clinical data of ONO/GS-4059...
October 20, 2016: Oncotarget
Zhihong Hu, L Jeffrey Medeiros, Zi Chen, Weina Chen, Shaoying Li, Sergej N Konoplev, Xinyan Lu, Lan V Pham, Ken H Young, Wei Wang, Shimin Hu
MYC rearrangement in mantle cell lymphoma (MCL) is rare, and its clinicopathologic significance is not well defined. We report 17 cases of MCL with 8q24/MYC rearrangement, detected at the time of initial diagnosis of MCL in 10 patients and subsequently during the clinical course in 7 patients. There were 12 men and 5 women with a median age of 61 years (range, 49 to 81 y). Fourteen patients had lymphadenopathy (Ann Arbor stage III/IV), and 3 patients presented with a leukemic pattern without lymphadenopathy...
October 21, 2016: American Journal of Surgical Pathology
Marilia N Siebert, Jacó J Mattos, Clei E Piazza, Daína de Lima, Carlos Henrique A M Gomes, Cláudio M R de Melo, Afonso C D Bainy
Cytochrome P450 family 1 (CYP1) is involved in polycyclic aromatic hydrocarbons (PAHs) biotransformation. PAHs can induce CYP1 protein expression and enzyme activity, the latter being usually quantified as 7-ethoxyresorufin O-deethylase activity (EROD). The aim of this study was to characterize EROD activity in the bivalve mollusk Crassostrea brasiliana. EROD activity was evaluated in cytosolic and microsomal fractions of gills, digestive gland and mantle of C. brasiliana. No EROD activity was detected in mantle, but it was present in microsomal fraction of gills and digestive gland with NADPH as coenzyme...
October 18, 2016: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Zhihao Jia, Huan Zhang, Shuai Jiang, Mengqiang Wang, Lingling Wang, Linsheng Song
C-type lectins (CTLs), a superfamily of Ca(2+)-dependent carbohydrate-recognition proteins, are involved in nonself-recognition and pathogen elimination, and play crucial roles in the innate immunity. In the present study, two single CRD C-type lectins, CgCLec-4 and CgCLec-5, were identified from oyster Crassostrea gigas. The open reading frame (ORF) of CgCLec-4 and CgCLec-5 encoded polypeptides of 152 and 150 amino acids, respectively. Both CgCLec-4 and CgCLec-5 contained one CRD with six conserved cysteines to form three disulfide bridges...
October 17, 2016: Fish & Shellfish Immunology
A A H Bressers, N A Goto, S Piepers, J C Regelink
BACKGROUND: Autoimmune encephalitis is a rare condition characterized by subacute development of cognitive and psychiatric symptoms. A paraneoplastic syndrome involves autoimmune encephalitis caused by classic antibodies. Although this condition is often associated with cancer, no malignancy has yet been found in 70-90% of patients at the time of diagnosis. CASE DESCRIPTION: We saw a 58-year-old male patient with fatigue, diarrhoea and weight loss. He was also experiencing hyperekplexia, personality changes and an instable gait...
2016: Nederlands Tijdschrift Voor Geneeskunde
Ding Pan, Giulia Galli
Investigating the fate of dissolved carbon dioxide under extreme conditions is critical to understanding the deep carbon cycle in Earth, a process that ultimately influences global climate change. We used first-principles molecular dynamics simulations to study carbonates and carbon dioxide dissolved in water at pressures (P) and temperatures (T) approximating the conditions of Earth's upper mantle. Contrary to popular geochemical models assuming that molecular CO2(aq) is the major carbon species present in water under deep Earth conditions, we found that at 11 GPa and 1000 K, carbon exists almost entirely in the forms of solvated carbonate ([Formula: see text]) and bicarbonate ([Formula: see text]) ions and that even carbonic acid [H2CO3(aq)] is more abundant than CO2(aq)...
October 2016: Science Advances
Ryan J Gallacher, Derek Keir, Nicholas Harmon, Graham Stuart, Sylvie Leroy, James O S Hammond, J-Michael Kendall, Atalay Ayele, Berhe Goitom, Ghebrebrhan Ogubazghi, Abdulhakim Ahmed
Melting of the mantle during continental breakup leads to magmatic intrusion and volcanism, yet our understanding of the location and dominant mechanisms of melt generation in rifting environments is impeded by a paucity of direct observations of mantle melting. It is unclear when during the rifting process the segmented nature of magma supply typical of seafloor spreading initiates. Here, we use Rayleigh-wave tomography to construct a high-resolution absolute three-dimensional shear-wave velocity model of the upper 250 km beneath the Afar triple junction, imaging the mantle response during progressive continental breakup...
October 18, 2016: Nature Communications
Matthew D Seftel, John Kuruvilla, Tom Kouroukis, Versha Banerji, Graeme Fraser, Michael Crump, Rajat Kumar, Haji I Chalchal, Muhammad Salim, Rob C Laister, Susan Crocker, Spencer B Gibson, Marcia Toguchi, John F Lyons, Hao Xu, Jean Powers, Joana Sederias, Lesley Seymour, Annette E Hay
AT7519M is a small molecule inhibitor of cyclin-dependent kinases 1, 2, 4, 5, and 9 with in vitro activity against lymphoid malignancies. In two concurrent Phase II trials, we evaluated AT7519M in relapsed or refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) using the recommended Phase II dosing of 27 mg/m(2) twice weekly for 2 of every 3 weeks. Primary objective was objective response rate (ORR). Nineteen patients were accrued (7 CLL, 12 MCL). Four CLL patients achieved stable disease (SD)...
October 17, 2016: Leukemia & Lymphoma
Noriyoshi Tsujino, Yu Nishihara, Daisuke Yamazaki, Yusuke Seto, Yuji Higo, Eiichi Takahashi
Seismic shear wave anisotropy is observed in Earth's uppermost lower mantle around several subducted slabs. The anisotropy caused by the deformation-induced crystallographic preferred orientation (CPO) of bridgmanite (perovskite-structured (Mg,Fe)SiO3) is the most plausible explanation for these seismic observations. However, the rheological properties of bridgmanite are largely unknown. Uniaxial deformation experiments have been carried out to determine the deformation texture of bridgmanite, but the dominant slip system (the slip direction and plane) has not been determined...
October 17, 2016: Nature
Caron Jacobson, Nadja Kopp, Jacob V Layer, Robert A Redd, Sebastian Tschuri, Sarah Haebe, Diederik van Bodegom, Liat Bird, Amanda L Christie, Alexandra Christodoulou, Amy Saur, Trevor Tivey, Stefanie Zapf, Deepak Bararia, Ursula Zimber-Strobl, Scott J Rodig, Oliver Weigert, David M Weinstock
The BTK inhibitor ibrutinib induces responses in 70% of patients with relapsed and refractory mantle cell lymphoma. Intrinsic resistance can occur through activation of the non-classical NFκB pathway and acquired resistance may involve the BTK C481S mutation. Outcomes after ibrutinib failure are dismal, indicating an unmet medical need. We reasoned that newer HSP90 inhibitors could overcome ibrutinib resistance by targeting multiple oncogenic pathways in MCL. HSP90 inhibition induced the complete degradation of both BTK and IKKα in MCL lines and CD40-dependent B cells, with downstream loss of MAP kinase and non-classical NFκB signaling...
October 14, 2016: Blood
Matthieu Hanf, David Chiron, Sophie de Visme, Cyrille Touzeau, Hervé Maisonneuve, Henry Jardel, Catherine Pellat-Deceunynck, Martine Amiot, Steven le Gouill
BACKGROUND: Mantle Cell Lymphoma (MCL) is often associated with progression, temporary response to therapy and a high relapse rate over time resulting in a poor long-term prognosis. Because MCL is classified as an incurable disease, therapeutic resistance is of great interest. However, knowledge about the biological mechanisms underlying resistance associated with MCL therapies and about associated predictors remains poor. The REFRACT-LYMA Cohort, a multicenter prospective cohort of patients with MCL, is set up to address this limitation...
October 14, 2016: BMC Cancer
Mainak Mookherjee, David Mainprice, Ketan Maheshwari, Olle Heinonen, Dhenu Patel, Anant Hariharan
Albite (NaAlSi3O8) is an aluminosilicate mineral. Its crystal structure consists of 3-D framework of Al and Si tetrahedral units. We have used Density Functional Theory to investigate the high-pressure behavior of the crystal structure and how it affects the elasticity of albite. Our results indicate elastic softening between 6-8 GPa. This is observed in all the individual elastic stiffness components. Our analysis indicates that the softening is due to the response of the three-dimensional tetrahedral framework, in particular by the pressure dependent changes in the tetrahedral tilts...
October 13, 2016: Scientific Reports
Anshuman Singh, Michael Padilla, Eric M Nyberg, Mary Chocas, Oke Anakwenze, Raffy Mirzayan, Edward H Yian, Ronald A Navarro
BACKGROUND: Tuberosity healing correlates with clinical outcomes after hemiarthroplasty for 4-part proximal humeral fractures (4PHFs). We seek to examine variables that affect tuberosity healing. METHODS: This was a retrospective comparative study. At 1 year postoperatively, patients who underwent hemiarthroplasty for 4PHFs were divided into 2 groups: those with anatomically healed tuberosities and those with tuberosity nonunion. The primary variables included time between injury and surgery, prosthesis fenestration, cement mantle classification, and both vertical and horizontal tuberosity reduction...
October 7, 2016: Journal of Shoulder and Elbow Surgery
Narangoo Purevjav, Takuo Okuchi, Naotaka Tomioka, Xiaoping Wang, Christina Hoffmann
Evidence from seismological and mineralogical studies increasingly indicates that water from the oceans has been transported to the deep earth to form water-bearing dense mantle minerals. Wadsleyite [(Mg, Fe(2+))2SiO4] has been identified as one of the most important host minerals incorporating this type of water, which is capable of storing the entire mass of the oceans as a hidden reservoir. To understand the effects of such water on the physical properties and chemical evolution of Earth's interior, it is essential to determine where in the crystal structure the hydration occurs and which chemical bonds are altered and weakened after hydration...
October 11, 2016: Scientific Reports
Ying Huang, Wen Wang, Qian Ren
C1q is the target recognition sequence of the classical complement pathway and a major link that connects innate and acquired immunity. In this study, a C1qDC homolog, HcC1qDC5, from the triangle-shell pearl mussel (Hyriopsis cumingii) was identified. The complete nucleotide sequence of HcC1qDC5 cDNA consists of a 5'-untranslated terminal region (UTR) of 123 bp, a 3'-UTR of 105 bp with a poly(A) tail, and an open reading frame (ORF) of 1344 bp, which encodes a polypeptide of 447 amino acids. HcC1qDC5 contains a signal peptide and three typical C1q domains...
October 8, 2016: Fish & Shellfish Immunology
Sagar Masuti, Sylvain D Barbot, Shun-Ichiro Karato, Lujia Feng, Paramesh Banerjee
Water, the most abundant volatile in Earth's interior, preserves the young surface of our planet by catalysing mantle convection, lubricating plate tectonics and feeding arc volcanism. Since planetary accretion, water has been exchanged between the hydrosphere and the geosphere, but its depth distribution in the mantle remains elusive. Water drastically reduces the strength of olivine and this effect can be exploited to estimate the water content of olivine from the mechanical response of the asthenosphere to stress perturbations such as the ones following large earthquakes...
October 10, 2016: Nature
Yan Hu, Roland Bürgmann, Paramesh Banerjee, Lujia Feng, Emma M Hill, Takeo Ito, Takao Tabei, Kelin Wang
The concept of a weak asthenospheric layer underlying Earth's mobile tectonic plates is fundamental to our understanding of mantle convection and plate tectonics. However, little is known about the mechanical properties of the asthenosphere (the part of the upper mantle below the lithosphere) underlying the oceanic crust, which covers about 60 per cent of Earth's surface. Great earthquakes cause large coseismic crustal deformation in areas hundreds of kilometres away from and below the rupture area. Subsequent relaxation of the earthquake-induced stresses in the viscoelastic upper mantle leads to prolonged postseismic crustal deformation that may last several decades and can be recorded with geodetic methods...
October 10, 2016: Nature
Gabriele Cazzoli, Valerio Lattanzi, Till Kirsch, Jürgen Gauss, Belén Tercero, José Cernicharo, Cristina Puzzarini
CONTEXT: Despite the fact that many sulfur-bearing molecules, ranging from simple diatomic species up to astronomical complex molecules, have been detected in the interstellar medium, the sulfur chemistry in space is largely unknown and a depletion in the abundance of S-containing species has been observed in the cold, dense interstellar medium (ISM). The chemical form of the missing sulfur has yet to be identified. AIMS: For these reasons, in view of the fact that there is a large abundance of triatomic species harbouring sulfur, oxygen, and hydrogen, we decided to investigate the HSO radical in the laboratory to try its astronomical detection...
July 2016: Astronomy and Astrophysics
Simona Righi, Stefano Pileri, Claudio Agostinelli, Francesco Bacci, Sebastiano Spagnolo, Elena Sabattini
Mantle cell lymphoma (MCL) usually harbor the t(11;14)(q13;q32) with overexpression of CCND1 mRNA and transcription of the cyclin D1 nuclear protein. Regardless CCND1 status, most MCLs also express the SOX11 nuclear protein, which is thus helpful in the diagnosis of the rare CCND1 negative MCLs. Recently, SOX11 has been reported to be often negative in MCLs clinically resembling marginal zone lymphoma and recently defined as "leukemic non-nodal" MCL in the incoming revision of the WHO Classification of lymphoid tumors, for which the bone marrow biopsy is commonly the first diagnostic approach...
October 5, 2016: Human Pathology
J J Wen, Z B Liu, C G Xu
Objective: To determine the anti-tumor effects of 13-cis-retinoic acid (13cRA) combined with interferonα-2b (IFNα-2b) in mantle cell lymphoma (MCL) animal model. Methods: The animal model of MCL was established by introducing Jeko-1 cell line into severe combined immunodeficiency disease mice. The successfully tumor-developed mice were assigned to different groups treated with negative control group (solvents), 13cRA (high dose: 200mg/kg; middle dose: 100mg/kg; low dose: 50 mg/kg) alone, IFNα-2b alone or combination of different dose of 13cRA with IFNα-2b, and positive control group (bortezomib, rituximab, cyclophosphamide), respectively...
September 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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