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https://www.readbyqxmd.com/read/28646117/cyclin-dependent-kinase-9-is-a-novel-specific-molecular-target-in-adult-t-cell-leukemia-lymphoma
#1
Tomoko Narita, Takashi Ishida, Asahi Ito, Ayako Masaki, Shiori Kinoshita, Susumu Suzuki, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Kazunori Imada, Yuetsu Tanaka, Takaori-Kondo Akifumi, Hiroshi Inagaki, Arne Scholz, Philip Lienau, Taruho Kuroda, Ryuzo Ueda, Shinsuke Iida
Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the carboxy-terminal domain (CTD) of RNA polymerase II (RNAPII).  The deregulation of CDK9/P-TEFb has important implications for many cancer types.  BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase I studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL)...
June 23, 2017: Blood
https://www.readbyqxmd.com/read/28645916/structures-and-dynamics-of-hibernating-ribosomes-from-staphylococcus-aureus-mediated-by-intermolecular-interactions-of-hpf
#2
Iskander Khusainov, Quentin Vicens, Rustam Ayupov, Konstantin Usachev, Alexander Myasnikov, Angelita Simonetti, Shamil Validov, Bruno Kieffer, Gulnara Yusupova, Marat Yusupov, Yaser Hashem
In bacteria, ribosomal hibernation shuts down translation as a response to stress, through reversible binding of stress-induced proteins to ribosomes. This process typically involves the formation of 100S ribosome dimers. Here, we present the structures of hibernating ribosomes from human pathogen Staphylococcus aureus containing a long variant of the hibernation-promoting factor (SaHPF) that we solved using cryo-electron microscopy. Our reconstructions reveal that the N-terminal domain (NTD) of SaHPF binds to the 30S subunit as observed for shorter variants of HPF in other species...
June 23, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28644728/liposomes-equipped-with-cell-penetrating-peptide-br2-enhances-chemotherapeutic-effects-of-cantharidin-against-hepatocellular-carcinoma
#3
Xue Zhang, Congcong Lin, Aiping Lu, Ge Lin, Huoji Chen, Qiang Liu, Zhijun Yang, Hongqi Zhang
A main hurdle for the success of tumor-specific liposomes is their inability to penetrate tumors efficiently. In this study, we incorporated a cell-penetrating peptide BR2 onto the surface of a liposome loaded with the anticancer drug cantharidin (CTD) to create a system targeting hepatocellular carcinoma (HCC) cells more efficiently and effectively. The in vitro cytotoxicity assay comparing the loaded liposomes' effects on hepatocellular cancer HepG2 and the control Miha cells showed that CTD-loaded liposomes had a stronger anticancer effect after BR2 modification...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28642621/variants-of-the-abca3-gene-might-contribute-to-susceptibility-to-interstitial-lung-diseases-in-the-chinese-population
#4
Wei Zhou, Yi Zhuang, Jiapeng Sun, Xiaofen Wang, Qingya Zhao, Lizhi Xu, Yaping Wang
ATP-binding cassette A3 (ABCA3) is a phospholipid carrier that is mainly expressed in the alveolar epithelium. Biallelic mutations of ABCA3 has been associated with fatal respiratory distress syndrome and interstitial lung disease (ILD) in children. However, whether variations in ABCA3 have a role in the development of adult ILD, including idiopathic pulmonary fibrosis (IPF), remains to be addressed. In this study, we screened for germline variants of ABCA3 by exons-sequencing in 30 patients with sporadic IPF and in 30 matched healthy controls...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28636891/comparison-of-cyclophosphamide-thalidomide-dexamethasone-to-bortezomib-cyclophosphamide-dexamethasone-as-induction-therapy-for-multiple-myeloma-patients-in-brazil
#5
Suelen Vigolo, Joice Zuckermann, Rosane Isabel Bittencourt, Lúcia Silla, Diogo André Pilger
OBJECTIVE/BACKGROUND: Chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) remains the standard treatment for multiple myeloma (MM). Thalidomide or bortezomib may be combined with cyclophosphamide and dexamethasone, in what are known as the CTD and VCD protocols, respectively. The objective of this study was to evaluate the clinical characteristics and response rates obtained with CTD and VCD, observing whether the inclusion of bortezomib to treat MM patients in Brazil increases therapeutic efficiency...
June 15, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28633258/stepwise-total-aortic-repairs-with-fenestrated-endografts-in-a-patient-with-loeys-dietz-syndrome
#6
Kenichi Hashizume, Hideyuki Shimizu, Masanori Honda, Shinya Inoue, Hidenobu Takaki, Kanako Hayashi, Hiroaki Kaneyama
Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder (CTD) caused by mutations in the gene encoding transforming growth factor-β receptors Ⅰ and Ⅱ. Patients with LDS manifest spontaneous aneurysms and dissections of the aorta and peripheral artery. We report a successful treatment with a hybrid endovascular repair for a rapidly expanding thoracoabdominal aneurysm in a 41-year-old woman affected by LDS. To overcome the difficulties of anatomical and surgical repair, we applied an original strategy using surgeon-modified fenestrated endografts...
July 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28621907/role-of-cleavage-and-polyadenylation-specificity-factor-100-anchoring-poly-a-sites-and-modulating-transcription-termination
#7
Juncheng Lin, Ruqiang Xu, Xiaohui Wu, Yingjia Shen, Qingshun Q Li
CPSF100 is a core component of the Cleavage and Polyadenylation Specificity Factor (CPSF) complex for the 3'-end formation of mRNA, but it still has no clear functional assignment. CPSF100 was reported to play a role in RNA silencing and promote flowering in Arabidopsis. However, the molecular mechanisms underlying these phenomena are not fully understood. Our genetics analyses indicate that plants with a hypomorphic mutant of CPSF100 (esp5) show defects in embryogenesis, reduced seed production, or altered root morphology...
June 16, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28619061/rituximab-versus-cyclophosphamide-for-the-treatment-of-connective-tissue-disease-associated-interstitial-lung-disease-recital-study-protocol-for-a-randomised-controlled-trial
#8
Peter Saunders, Vicky Tsipouri, Gregory J Keir, Deborah Ashby, Marcus D Flather, Helen Parfrey, Daphne Babalis, Elisabetta A Renzoni, Christopher P Denton, Athol U Wells, Toby M Maher
BACKGROUND: Interstitial lung disease (ILD) frequently complicates systemic autoimmune disorders resulting in considerable morbidity and mortality. The connective tissue diseases (CTDs) most frequently resulting in ILD include: systemic sclerosis, idiopathic inflammatory myositis (including dermatomyositis, polymyositis and anti-synthetase syndrome) and mixed connective tissue disease. Despite the development, over the last two decades, of a range of biological therapies which have resulted in significant improvements in the treatment of the systemic manifestations of CTD, the management of CTD-associated ILD has changed little...
June 15, 2017: Trials
https://www.readbyqxmd.com/read/28618399/rna-sequencing-investigation-identifies-an-effective-risk-score-generated-by-three-novel-lncrnas-for-the-survival-of-papillary-thyroid-cancer-patients
#9
Yi-Huan Luo, Liang Liang, Rong-Quan He, Dong-Yue Wen, Guo-Fei Deng, Hong Yang, Yun He, Wei Ma, Xiao-Yong Cai, Jun-Qiang Chen, Gang Chen
Scholars are striving to apply molecular biology involving long non-coding RNA (lncRNA) in the prognostication of papillary thyroid cancer (PTC). However, the clinical role of lncRNAs in the prognostic setting of PTC is still unclear. Herein, a comprehensive inquiry was performed to screen lncRNA expression profiling with 507 PTC patients from The Cancer Genome Atlas RNA-sequencing datasets. A total of 734 lncRNAs were detected to be aberrantly expressed, among which three novel lncRNAs including AC079630.2, CRNDE and CTD-2171N6...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614213/pathologic-separation-of-chronic-hypersensitivity-pneumonitis-from-fibrotic-connective-tissue-disease-associated-interstitial-lung-disease
#10
Andrew Churg, Joanne L Wright, Christopher J Ryerson
Chronic (fibrotic) hypersensitivity pneumonitis (HP) and fibrosing interstitial pneumonias associated with connective tissue disease (CTD-ILD) can be difficult to distinguish in biopsy specimens. To investigate features that might separate these entities, 2 pathologists blinded to the diagnoses reviewed 16 cases of chronic HP and 12 cases of CTD-ILD. Fifteen predefined parameters were examined by morphometric point counting, analysis/cm of lung tissue, or presence/absence. Germinal centers were present in a minority of patients, but favored a diagnosis of CTD-ILD (7/12 CTD vs...
June 13, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28612517/two-dimensional-knowledge-based-volumetric-reconstruction-of-the-right-ventricle-documents-short-term-improvement-in-pulmonary-hypertension
#11
Johannes P Schwaiger, Daniel S Knight, Thomas Kaier, Adele Gallimore, Christopher P Denton, Benjamin E Schreiber, Clive Handler, John G Coghlan
BACKGROUND: Data are scarce about short-term right ventricular changes in pulmonary hypertension. Two-dimensional knowledge-based reconstruction of the right ventricle with 2D echocardiography (2DKBR) has been shown to be a valid alternative to Cardiac MRI. PATIENTS AND METHODS: In this longitudinal study 25 pulmonary hypertension patients underwent 2DKBR of the right ventricle, assessment of NT-proBNP levels and functional class at baseline and after a mean follow-up of 6...
June 2017: Echocardiography
https://www.readbyqxmd.com/read/28603700/the-type-ix-secretion-system-t9ss-highlights-and-recent-insights-into-its-structure-and-function
#12
REVIEW
Anna M Lasica, Miroslaw Ksiazek, Mariusz Madej, Jan Potempa
Protein secretion systems are vital for prokaryotic life, as they enable bacteria to acquire nutrients, communicate with other species, defend against biological and chemical agents, and facilitate disease through the delivery of virulence factors. In this review, we will focus on the recently discovered type IX secretion system (T9SS), a complex translocon found only in some species of the Bacteroidetes phylum. T9SS plays two roles, depending on the lifestyle of the bacteria. It provides either a means of movement (called gliding motility) for peace-loving environmental bacteria or a weapon for pathogens...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28603484/evolutionary-divergence-of-the-c-terminal-domain-of-complexin-accounts-for-functional-disparities-between-vertebrate-and-invertebrate-complexins
#13
Rachel T Wragg, Daniel A Parisotto, Zhenlong Li, Mayu S Terakawa, David Snead, Ishani Basu, Harel Weinstein, David Eliezer, Jeremy S Dittman
Complexin is a critical presynaptic protein that regulates both spontaneous and calcium-triggered neurotransmitter release in all synapses. Although the SNARE-binding central helix of complexin is highly conserved and required for all known complexin functions, the remainder of the protein has profoundly diverged across the animal kingdom. Striking disparities in complexin inhibitory activity are observed between vertebrate and invertebrate complexins but little is known about the source of these differences or their relevance to the underlying mechanism of complexin regulation...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28597880/the-transient-manifold-structure-of-the-p53-extreme-c-terminal-domain-insight-into-disorder-recognition-and-binding-promiscuity-by-molecular-dynamics-simulations
#14
E Fadda, M G Nixon
The p53 tumour suppressor is a transcription activator that signals for cell cycle arrest and apoptosis. In its active form p53 is a tetramer, with each monomer organised in domains with different degrees of structural stability, ranging from the well folded DNA-binding domain (DBD) and tetramerization domain (TET), to the intrinsically disordered transactivation domain (TAD), and extreme C-terminal domain (CTD). Compared to all other domains, the structure/function relationship of the p53-CTD within the full-length p53 tetramer is still poorly understood due to its high degree of conformational disorder...
June 9, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28596722/unique-structural-features-of-membrane-bound-c-terminal-domain-motifs-modulate-complexin-inhibitory-function
#15
David Snead, Alex L Lai, Rachel T Wragg, Daniel A Parisotto, Trudy F Ramlall, Jeremy S Dittman, Jack H Freed, David Eliezer
Complexin is a small soluble presynaptic protein that interacts with neuronal SNARE proteins in order to regulate synaptic vesicle exocytosis. While the SNARE-binding central helix of complexin is required for both the inhibition of spontaneous fusion and the facilitation of synchronous fusion, the disordered C-terminal domain (CTD) of complexin is specifically required for its inhibitory function. The CTD of worm complexin binds to membranes via two distinct motifs, one of which undergoes a membrane curvature dependent structural transition that is required for efficient inhibition of neurotransmitter release, but the conformations of the membrane-bound motifs remain poorly characterized...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28595349/prenatal-exposure-to-antimalarials-decreases-the-risk-of-cardiac-but-not-non-cardiac-neonatal-lupus-a-single-centre-cohort-study
#16
Julie Barsalou, Edgar Jaeggi, Carl A Laskin, Patrick Brown, Simon Y Tian, Robert M Hamilton, Earl D Silverman
Objective: . Recent studies have suggested that prenatal exposure to HCQ reduces the risk of cardiac neonatal lupus. The aim of this study is to assess if maternal intake of antimalarials (AMs) throughout pregnancy lowered the risk of cardiac and non-cardiac neonatal lupus. Methods: . Consecutive children seen between 1 January 1984 to 1 October 2013 born to women with a CTD and positive anti-Ro and/or anti-La antibodies were eligible for this single-centre retrospective cohort study...
June 8, 2017: Rheumatology
https://www.readbyqxmd.com/read/28594866/revisiting-the-co-existence-of-attention-deficit-hyperactivity-disorder-and-chronic-tic-disorder-in-childhood-the-case-of-colour-discrimination-sustained-attention-and-interference-control
#17
Henrik Uebel-von Sandersleben, Björn Albrecht, Aribert Rothenberger, Anke Fillmer-Heise, Veit Roessner, Joseph Sergeant, Rosemary Tannock, Tobias Banaschewski
OBJECTIVE: Attention Deficit / Hyperactivity Disorder (ADHD) and Chronic Tic Disorder (CTD) are two common and frequently co-existing disorders, probably following an additive model. But this is not yet clear for the basic sensory function of colour processing sensitive to dopaminergic functioning in the retina and higher cognitive functions like attention and interference control. The latter two reflect important aspects for psychoeducation and behavioural treatment approaches. METHODS: Colour discrimination using the Farnsworth-Munsell 100-hue Test, sustained attention during the Frankfurt Attention Inventory (FAIR), and interference liability during Colour- and Counting-Stroop-Tests were assessed to further clarify the cognitive profile of the co-existence of ADHD and CTD...
2017: PloS One
https://www.readbyqxmd.com/read/28587231/a-novel-lid-covering-peptide-inhibitor-of-nicotinic-acetylcholine-receptors-derived-from-%C3%AE-d-conotoxin-gexxa
#18
Longjin Yang, Han-Shen Tae, Zhou Fan, Xiaoxia Shao, Shaoqiong Xu, Suwen Zhao, David J Adams, Chunguang Wang
Nicotinic acetylcholine receptors (nAChRs) play a fundamental role in nervous signal transmission, therefore various antagonists and agonists are highly desired to explore the structure and function of nAChRs. Recently, a novel dimeric αD-conotoxin GeXXA was identified to inhibit nAChRs by binding at the top surface of the receptors, and the monomeric C-terminal domain (CTD) of αD-GeXXA retains some inhibitory activity. In this study, the internal dimeric N-terminal domain (NTD) of this conopeptide was further investigated...
June 5, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28582412/accuracy-of-parasitological-and-immunological-tests-for-the-screening-of-human-schistosomiasis-in-immigrants-and-refugees-from-african-countries-an-approach-with-latent-class-analysis
#19
Anna Beltrame, Massimo Guerriero, Andrea Angheben, Federico Gobbi, Ana Requena-Mendez, Lorenzo Zammarchi, Fabio Formenti, Francesca Perandin, Dora Buonfrate, Zeno Bisoffi
BACKGROUND: Schistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28580923/the-crystal-structure-of-human-deah-box-rna-helicase-15-reveals-a-domain-organization-of-the-mammalian-deah-rha-family
#20
Karin Murakami, Kenji Nakano, Toshiyuki Shimizu, Umeharu Ohto
DEAH-box RNA helicase 15 (DHX15) plays important roles in RNA metabolism, including in splicing and in ribosome biogenesis. In addition, mammalian DHX15 also mediates the innate immune sensing of viral RNA. However, structural information on this protein is not available, although the structure of the fungal orthologue of this protein, Prp43, has been elucidated. Here, the crystal structure of the ADP-bound form of human DHX15 is reported at a resolution of 2.0 Å. This is the first structure to be revealed of a member of the mammalian DEAH-box RNA helicase (DEAH/RHA) family in a nearly complete form, including the catalytic core consisting of the two N-terminal RecA domains and the C-terminal regulatory domains (CTD)...
June 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
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